The DOI matches its Crossref record; 230 of the 242 references it cites were found in a registry or an index; 195 of the 238 sources its claims cite were checked for support.
Cellular senescence and senolytics: the path to the clinic
Open accessAbstract
Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases. One such process is cellular senescence, which entails a state of cell cycle arrest in response to damaging stimuli. Senescent cells can arise throughout the lifespan and, if persistent, can have deleterious effects on tissue function due to the many proteins they secrete. In preclinical models, interventions targeting those senescent cells that are persistent and cause tissue damage have been shown to delay, prevent or alleviate multiple disorders. In line with this, the discovery of small-molecule senolytic drugs that selectively clear senescent cells has led to promising strategies for preventing or treating multiple diseases and age-related conditions in humans. In this Review, we outline the rationale for senescent cells as a therapeutic target for disorders across the lifespan and discuss the most promising strategies—including recent and ongoing clinical trials—for translating small-molecule senolytics and other senescence-targeting interventions into clinical use. Cellular senescence has emerged as a promising therapeutic target for disorders across the lifespan; this Review highlights the most promising strategies for translating senescence-targeting interventions into clinical use in the near future.
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Claims the paper makes
66 Partly supported · 20 Supported · 18 No basis given · 16 Own interpretation · 11 No full text of the sources · 8 Sources not found · 1 Supported so far · 1 Not checked yet · 1 Own result · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“fundamental aging processes can operate even before conception, for example, in the context of aged oocytes linked to Down syndrome12,13.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Supportedcites [12] Igarashi, H., Takahashi, T. & Nagase, S. Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies. Reprod. Med. Biol. 14, 159–169 (2015). source
The Introduction links oocyte aging to chromosomal abnormalities and birth defects. The section “Effects of oocyte aging on mitochondria” specifically discusses maternal age-related trisomy, including Down’s syndrome, in connection with errors during oocyte meiosis. Page numbers are not provided in our copy. (LLM, conf=0.91)
- Partly supportedcites [13] Meharena, H. S. et al. Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors. Cell Stem Cell 29, 116–130 (2022). sourceExperimental — accuracy not yet measured
The Results section, “T21 induces NPC senescence” (page unavailable), reports senescence in Down-syndrome neural progenitor cells, supporting a link between Down syndrome and a process associated with aging. It does not examine aged oocytes or establish that the process operates before conception; searches for oocytes, maternal age, and preconception did not find support for that part of the claim. (LLM, conf=0.83)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronological age is the major predictor for most of the diseases that account for the bulk of morbidity, mortality and health costs across low-, middle- and high-income countries2–7.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Not checked — no full text of the sourcecites [2] Niccoli, T. & Partridge, L. Ageing as a risk factor for disease. Curr. Biol. 22, R741–R752 (2012). source
- Partly supportedcites [3] Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014). sourceExperimental — accuracy not yet measured
The Introduction calls aging the predominant risk factor for most diseases that limit healthspan, and the Aging Research Initiative describes chronic diseases as the majority of global disease burden and the most common causes of mortality. The paper also calls chronic diseases of aging a major global healthcare burden, but our copy does not establish the claim separately for low-, middle-, and high-income countries or explicitly identify chronological age as the predictor. (LLM, conf=0.85)
- Partly supportedcites [4] Scott, A. J., Ellison, M. & Sinclair, D. A. The economic value of targeting aging. Nat. Aging 1, 616–623 (2021). sourceExperimental — accuracy not yet measured
The Main section links rising age with frailty, disability and deaths, while the Results section models mortality risk and health deficits as increasing exponentially with age. But the paper uses US data and does not establish that chronological age is the major predictor of most diseases or associated health costs across low-, middle- and high-income countries. Page numbers are unavailable in our copy. (LLM, conf=0.84)
- Partly supportedcites [5] St Sauver, J. L. et al. Risk of developing multimorbidity across all ages in an historical cohort study: differences by sex and ethnicity. BMJ Open 5, e006413 (2015). sourceExperimental — accuracy not yet measured
The Results (Description of the Olmsted County population; page unavailable) report that incidence of most of the 20 studied chronic conditions increased steeply with age. The paper does not establish that age is the major predictor of diseases accounting for most morbidity, mortality and costs, or extend that finding across low-, middle- and high-income countries. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [6] Tchkonia, T., Palmer, A. K. & Kirkland, J. L. New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 106, e1481–e1487 (2021). source
- Supportedcites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). source
Section 2, “Aging, Chronic Diseases, and Cellular Senescence,” calls aging the major risk factor for most chronic diseases responsible for the bulk of morbidity, mortality, and health costs in developed and developing worlds. This supports the citing sentence’s paraphrase; the copy does not give a page number. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Supportedcites [3] Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014). source
The Pillars of Aging section describes the processes driving aging as “highly intertwined.” The Conclusions section calls aging a common cause of chronic disease, and the Aging Research Initiative says aging enables pathology across multiple chronic diseases. Page numbers are not available in our copy. (LLM, conf=0.90)
- Supportedcites [15] Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013). source
The Abstract identifies aging as the primary risk factor for major human pathologies. Conclusions and Perspectives describes the hallmarks as interconnected and proposes that some initiate accumulating damage. Together, these passages support the hedged claim that interlinked aging processes contribute to many disorders. (LLM, conf=0.87)
- Partly supportedcites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). sourceExperimental — accuracy not yet measured
The paper’s Abstract (page unavailable) identifies cellular senescence as a mechanism driving aging and age-related diseases, and says senescent cells play a causal role in preclinical models. It does not establish the broader claim that multiple interlinked aging processes are root-cause contributors to many disorders and diseases. (LLM, conf=0.83)
- Partly supportedcites [17] Hadley, E. C., Kuchel, G. A., Newman, A. B. & Workshop Speakers and Participants. Report: NIA workshop on measures of physiologic resiliencies in human aging. J. Gerontol. A Biol. Sci. Med. Sci. 72, 980–990 (2017). sourceExperimental — accuracy not yet measured
The “Mechanistic Studies” section says basic aging mechanisms may act individually or collectively and influence a wide variety of aging-related outcomes. The “Influence of Biologic Aging Mechanisms on Resilience” section says they could contribute to declining clinical and physiologic resilience. Neither section establishes that these processes are root-cause contributors to many disorders and diseases; the paper frames their influence as a subject for further research. The supplied passages give no page numbers. (LLM, conf=0.82)
- Partly supportedcites [18] Dungan, C. M. et al. Senolytic treatment rescues blunted muscle hypertrophy in old mice. Geroscience https://doi.org/10.1007/s11357-022-00542-2 (2022). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) links several aging-related mechanisms to anabolic resistance in skeletal muscle, and the Discussion reports that clearing senescent cells restores muscle growth in old mice. These passages support a contribution to one age-related condition, but not the broader claim that interlinked aging processes are root-cause contributors to many disorders and diseases. (LLM, conf=0.85)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Aging progresses throughout the lifespan can be accentuated at etiologic sites of multiple acute and chronic diseases, including in children6,8–12.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Tchkonia, T., Palmer, A. K. & Kirkland, J. L. New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 106, e1481–e1487 (2021). source
- Partly supportedcites [8] Wissler Gerdes, E. O. et al. Cellular senescence in aging and age-related diseases: implications for neurodegenerative diseases. Int. Rev. Neurobiol. 155, 203–234 (2020). sourceExperimental — accuracy not yet measured
The Introduction links cellular senescence to several chronic diseases, and the Brain tumors section says chemoradiation can induce senescence with damaging effects in pediatric patients (page numbers unavailable). The paper also discusses senescence after stroke. These passages support examples of disease- and treatment-associated senescence, but not the broader claim that aging processes are accentuated at the etiologic sites of multiple acute and chronic diseases, including in children. (LLM, conf=0.82)
- Partly supportedcites [9] Ness, K. K. et al. Frailty in childhood cancer survivors. Cancer 121, 1540–1547 (2015). sourceExperimental — accuracy not yet measured
The Frailty section (page unavailable) says that age-related functional decline can accelerate after acute illness or injury, especially when organ systems are damaged. Potential biological markers of frail health (page unavailable) describes vulnerability in organs exposed to cancer-treatment toxins in children. The paper does not establish the broader claim that aging is accentuated at etiologic sites of multiple acute and chronic diseases generally, including in children outside the childhood-cancer context. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [10] Munoz-Espin, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482–496 (2014). source
- Partly supportedcites [11] Suvakov, S. et al. Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies. EBioMedicine 70, 103536 (2021). sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports accelerated ageing-like changes and senescence in women with preeclampsia, including in placental and renal tissue. The Introduction links senescence more broadly to multiple chronic diseases. The paper does not establish the claim across multiple acute diseases or in children. (LLM, conf=0.86)
- Partly supportedcites [12] Igarashi, H., Takahashi, T. & Nagase, S. Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies. Reprod. Med. Biol. 14, 159–169 (2015). sourceExperimental — accuracy not yet measured
The ‘Contribution of oxidative stress to oocyte aging’ section (page not provided) links oxidative stress to aging and aging-related diseases, and the ‘Calorie restriction’ section names several such diseases. Neither section says that aging is accentuated at the etiologic sites of acute and chronic diseases or that this occurs in children. (LLM, conf=0.79)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Many such stressors activate DNA damage response signaling and activation of the p53/p21CIP1/WAF1, p16INK4a/retinoblastoma protein or other pathways, resulting in cell cycle arrest and the development of a senescence-associated secretory phenotype (SASP)24,40,48−53”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways
What the sources say
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says that stresses including DNA damage can induce senescence, which involves proliferative arrest, and that senescent cells can develop a SASP. It does not say that those stressors activate DNA damage response signaling or the specified p53/p21 and p16/RB pathways to produce those outcomes. (LLM, conf=0.86)
- Supportedcites [40] Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). source
The DNA Damage Response section (page unavailable) says unresolved DNA damage can lead to senescence and persistent DDR activates p53. The Cyclin-Dependent Kinase Inhibitors and Cell Cycle Arrest section identifies p16 and p21 as main drivers of senescent cell-cycle arrest; the paper also describes DDR as a major trigger of SASP signaling. Its qualification that not all senescence programs involve DDR is consistent with the claim’s “many,” rather than “all.” (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [48] Hickson, L. J. et al. Corrigendum to ‘Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease’ EBioMedicine 47 (2019) 446–456. EBioMedicine 52, 102595 (2020). source
- Partly supportedcites [49] Wang, B. et al. An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo. Nat. Aging 1, 962–973 (2021). sourceExperimental — accuracy not yet measured
The Introduction (page not available) says that stimuli including DNA damage can drive senescence through p16/Rb, p53/p21 and probably other pathways, with growth arrest and a SASP. It does not say that many of those stressors activate DNA damage response signaling, so that part of the attributed claim is not supported by our copy. (LLM, conf=0.85)
- Partly supportedcites [50] Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009). sourceExperimental — accuracy not yet measured
The paper’s Abstract (page unavailable in our copy) supports a pathway from persistent DNA damage signalling to p53-dependent growth arrest and a senescence-associated inflammatory cytokine response. It does not support the sentence’s implication that the p53/p21 or p16/RB arrest pathways themselves produce that response: it reports that the cytokine response is p53-independent and that p16-induced senescence without DNA damage does not initiate it. (LLM, conf=0.88)
- Partly supportedcites [51] Yousefzadeh, M. J. et al. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell 19, e13094 (2020). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says that several stressors induce senescence, describes entry through p53/p21, p16/pRB or GATA4 pathways, and defines senescence as proliferative arrest; it also says senescent cells can display a SASP. The paper does not establish the claim’s additional step that many of those stressors activate DNA damage response signaling. (LLM, conf=0.84)
- Supportedcites [52] Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019). source
The Macromolecular Damage section describes several senescence-inducing stresses that activate the DNA damage response, while noting that not all triggers do. The Cell-Cycle Arrest section links p53, p21, p16 and RB to arrest; the Secretion passage identifies the SASP as a hallmark with its own regulatory pathways. Together, these passages support the qualified claim. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [53] Sharpless, N. E. & Sherr, C. J. Forging a signature of in vivo senescence. Nat. Rev. Cancer 15, 397–408 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The senescent cell fate can be triggered by a number of stressors including DNA damage, cancerous mutations or oncogene activation, mitochondrial dysfunction, reactive metabolites, hyperoxia or hypoxia, proteotoxic stress, extracellular signals, infections, mechanical or shear stresses that deform cells, resistance exercise and factors secreted by other senescent cells18,38–47.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways
What the sources say
- Supportedcites [18] Dungan, C. M. et al. Senolytic treatment rescues blunted muscle hypertrophy in old mice. Geroscience https://doi.org/10.1007/s11357-022-00542-2 (2022). source
Among the stressors listed with multiple citations, this paper supports the resistance-exercise example. The Results report that senescent cells increased in human muscle 14 days after a bout of resistance exercise; the Discussion likewise says they emerged in response to exercise. (LLM, conf=0.88)
- Partly supportedcites [38] Yousefzadeh, M. J. et al. An aged immune system drives senescence and ageing of solid organs. Nature 594, 100–105 (2021). sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) says stress can activate senescence, and the Rapamycin rejuvenates immune cells section specifically links unrepaired endogenous DNA damage to immune-cell senescence. The Cell autonomous mechanism section also suggests aged splenocytes can drive senescence in other tissues. The paper does not establish the rest of the listed triggers, including oxygen extremes, mechanical stress and resistance exercise. (LLM, conf=0.88)
- Partly supportedcites [39] Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978–990 (2013). sourceExperimental — accuracy not yet measured
The Introduction and the section ‘Multiple components of the SASP mediate paracrine senescence’ support the claim that factors secreted by senescent cells can trigger senescence in other cells. The paper also studies oncogene-induced senescence and reports DNA and oxidative damage, but it does not establish the full list of triggers, including mitochondrial dysfunction, oxygen extremes, mechanical stress, infections, or resistance exercise. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)
- Partly supportedcites [40] Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). sourceExperimental — accuracy not yet measured
Box 1 (page unavailable) identifies DNA damage, oncogene activation, oxidative products, mitochondrial dysfunction, and factors secreted by senescent cells as causes of senescence. The copy does not establish resistance exercise, mechanical or shear stress, or oxygen extremes as triggers. Its discussion of infections and protein accumulation concerns ER stress, not a direct finding that they trigger senescence. (LLM, conf=0.88)
- Partly supportedcites [41] Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997). sourceExperimental — accuracy not yet measured
The Discussion and Concluding Remark report that oncogenic ras provokes premature senescence and discuss several other potential routes to a senescence-like state. The Introduction mentions DNA damage and hypoxia as triggers of increased p53, not as demonstrated triggers of senescence. The paper does not support the sentence’s wider list, including mitochondrial dysfunction, infections, mechanical stress, resistance exercise, and factors secreted by senescent cells. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [42] Chaib, S., Tchkonia, T. & Kirkland, J. L. in Handbook of Experimental Pharmacology (eds Eckel, J. & Clément, K.) 165–180 (Springer, 2021). source
- Partly supportedcites [43] Wiley, C. D. & Campisi, J. From ancient pathways to aging cells—connecting metabolism and cellular senescence. Cell Metab. 23, 1013–1021 (2016). sourceExperimental — accuracy not yet measured
The Introduction says that diverse stresses and physiological signals induce senescence, and the sections on mitochondrial dysfunction and oncogene-induced senescence identify those specific triggers. The copy also discusses genotoxic stress and ROS, but the passages do not establish the full attributed list, particularly infections, mechanical or shear stress, resistance exercise, and hypoxia as triggers. No page numbers were supplied for these sections. (LLM, conf=0.88)
- Partly supportedcites [44] Tripathi, U. et al. SARS-CoV-2 causes senescence in human cells and exacerbates the senescence-associated secretory phenotype through TLR-3. Aging 13, 21838–21854 (2021). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) identifies damage signals, metabolic insults, mechanical or shear forces, hypoxia, reactive oxygen species, oncogenes, and telomere damage as drivers of senescence. It also says factors secreted by senescent cells can induce secondary senescence, and the paper addresses viral infection. The copy does not identify resistance exercise, proteotoxic stress, or mitochondrial dysfunction as triggers; it describes reactive metabolites as SASP products rather than explicitly as triggers. (LLM, conf=0.88)
- Partly supportedcites [45] Lee, S. et al. Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature 599, 283–289 (2021). sourceExperimental — accuracy not yet measured
The Article section says that viral entry can trigger senescence and identifies activated oncogenes and DNA-damaging cancer therapy as other triggers. The Properties of VIS section also reports paracrine senescence induction. The paper does not support the full list attributed to it, including mitochondrial dysfunction, oxygen extremes, mechanical or shear stress, and resistance exercise (no page numbers provided). (LLM, conf=0.88)
- Partly supportedcites [46] Martini, H. & Passos, J. F. Cellular senescence: all roads lead to mitochondria. FEBS J. https://doi.org/10.1111/febs.16361 (2022). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) names DNA-damaging agents, oncogene activation, and mitochondrial dysfunction as senescence triggers, and says the senescence-associated secretory phenotype can transmit senescence to healthy cells. The cited paper does not support the full list attributed to it: the passages do not establish oxygen extremes, infections, mechanical or shear stress, or resistance exercise as triggers. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Normally, senescent cells appear to be cleared within days to weeks after they develop by natural killer cells and other immune cell types62,66–69.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > Adverse impacts of persistent, proapoptotic SASP-expressing senescent cells.
What the sources say
- Partly supportedcites [62] Prata, L., Ovsyannikova, I. G., Tchkonia, T. & Kirkland, J. L. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin. Immunol. 40, 101275 (2018). sourceExperimental — accuracy not yet measured
The Introduction says senescent cells appear to be usually cleared by the immune system, and the NKs section describes natural killer cells clearing senescent-like cells in a liver-fibrosis model, with fibrosis resolving within 20 days. That example does not establish that senescent cells generally are cleared within days to weeks after developing; the Heterogeneous SC hypothesis section also notes that some persist for years. Page numbers are unavailable in our copy. (LLM, conf=0.86)
- Partly supportedcites [66] Pereira, B. I. et al. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nat. Commun. 10, 2387 (2019). sourceExperimental — accuracy not yet measured
The Introduction says senescent cells can be eliminated by the immune system and identifies NK cells and other immune cells as participants in their surveillance. The Results also show that NK cells can target senescent fibroblasts in vitro. Neither passage establishes that senescent cells are normally cleared within days to weeks after developing. (LLM, conf=0.86)
- Partly supportedcites [67] Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007). sourceExperimental — accuracy not yet measured
The indexed paper (section labeled Abstract; page unavailable) reports that natural killer cells, neutrophils and macrophages contributed to clearance of senescent murine liver tumours after p53 restoration; the tumours became nearly undetectable within 12 days of treatment. It does not establish that senescent cells are normally cleared within days to weeks after they develop. The paper explicitly says it is unclear whether such turnover is a general feature of senescence in vivo. (LLM, conf=0.88)
- Partly supportedcites [68] Brighton, P. J. et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife 6, e31274 (2017). sourceExperimental — accuracy not yet measured
The Results section (‘Immune clearance of senescent decidual cells’; page unavailable) reports that uterine natural killer cells selectively clear senescent decidual cells, and notes a broader role for immune cells, especially NK cells, in eliminating senescent cells. It does not establish that senescent cells generally are cleared within days to weeks after they develop, or demonstrate clearance by other immune-cell types in this setting. (LLM, conf=0.86)
- Partly supportedcites [69] Stokes, K. L. et al. Natural killer cells limit the clearance of senescent lung adenocarcinoma cells. Oncogenesis 8, 24 (2019). sourceExperimental — accuracy not yet measured
The Discussion describes immune surveillance in which immune cells remove senescent cells, including examples involving NK cells and other immune cell types. The Results report substantial clearance within eight days after p53 reactivation. But the paper does not establish that senescent cells are normally cleared within days to weeks, and its lung adenocarcinoma findings show that NK cells dampen, rather than drive, clearance in that context. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This proapoptotic SASP can have detrimental effects both locally and systemically due to senescent cell accumulation and persistence24.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > The senescence-associated secretory phenotype.
What the sources say
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says that the SASP contributes to local and systemic dysfunction as senescent-cell burden rises. It describes the SASP as pro-inflammatory, however, not proapoptotic; that characterization is unsupported by our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Through upregulation of pro-survival and antiapoptotic pathways such as SRC kinases, the PI3K-AKT signaling pathway, heat shock protein (HSP) pathways, serpines, mitochondrial pathways or apoptosis regulator BCL-2-related proteins, those senescent cells with a proapoptotic SASP can survive, despite the cytotoxic microenvironment they create6,7,14,34,35,54–58.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways
What the sources say
- Not checked — no full text of the sourcecites [6] Tchkonia, T., Palmer, A. K. & Kirkland, J. L. New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 106, e1481–e1487 (2021). source
- Partly supportedcites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). sourceExperimental — accuracy not yet measured
Section 4 (‘The Achilles’ Heel of Senescent Cells’; page unavailable) says senescent cells may rely on upregulated antiapoptotic pathways to withstand their own pro-apoptotic SASP. It identifies BCL-2, PI3K/AKT, serpine and tyrosine-kinase pathways; its table also names Src kinase. The copy does not identify HSP or a mitochondrial pathway as one of these survival pathways: it discusses mitochondrial dysfunction only as a possible reason for their upregulation. (LLM, conf=0.86)
- Partly supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). sourceExperimental — accuracy not yet measured
The Introduction says senescent cells survive despite apoptosis-inducing SASP factors, and the Results (The senescent transcriptome and anti-apoptotic pathways; Senolytic siRNAs) report increased anti-apoptotic gene sets and survival roles for PI3KCD, PAI-2 and BCL-xL. The Discussion also discusses PI3K–AKT and serpines. Our copy does not establish that SRC kinases or HSP pathways are upregulated to protect these cells, or demonstrate upregulation of every pathway in the citing sentence. (LLM, conf=0.87)
- Partly supportedcites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). sourceExperimental — accuracy not yet measured
The Discovery of senolytic drugs section says that senescent cells with a pro-apoptotic SASP depend on anti-apoptotic SCAP networks to avoid self-destruction, and it identifies Src kinase and BCL-2 family members as relevant targets. Our copy does not establish PI3K-AKT, HSP, or mitochondrial pathways as parts of those survival networks. The Cellular senescence section lists serpines as SASP factors associated with clotting and fibrosis, not as anti-apoptotic pathways. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [35] Tchkonia, T. & Kirkland, J. L. Aging, cell senescence and chronic disease: emerging therapeutic strategies. J. Am. Med. Assoc. 320, 1319–1320 (2018). source
- Partly supportedcites [54] Fuhrmann-Stroissnigg, H. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8, 422 (2017). sourceExperimental — accuracy not yet measured
The Results section ('HSP90 inhibitors downregulate the anti-apoptotic PI3K/AKT pathway'; page unavailable) says senescent cells upregulate survival signaling that resists apoptosis, and the Introduction names PI3K/AKT, serpine and Bcl-2 pathways. The Discussion also links HSP90 to that resistance. The cited paper does not establish the claim's SRC-kinase or mitochondrial pathways, or that a proapoptotic SASP creates the cytotoxic environment these cells survive. (LLM, conf=0.87)
- Partly supportedcites [55] Xu, Q. et al. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nat. Metab. 3, 1706–1726 (2021). sourceExperimental — accuracy not yet measured
The Results section on mitochondrial dysfunction reports elevated BCL-xL in senescent cells and implicates AKT signalling in their response to PCC1. The Discussion also identifies HSP90 and BCL-2-family inhibitors as senolytics. These passages do not establish that senescent cells survive a SASP-created cytotoxic environment by upregulating the full list of pathways, including SRC kinases and serpines. Page numbers are unavailable in our copy. (LLM, conf=0.85)
- Partly supportedcites [56] Wissler Gerdes, E. O., Zhu, Y., Tchkonia, T. & Kirkland, J. L. Discovery, development, and future application of senolytics: theories and predictions. FEBS J. 287, 2418–2427 (2020). sourceExperimental — accuracy not yet measured
In “The discovery of senolytics” (page not provided), the paper proposes that senescent cells resist their proapoptotic SASP and identifies PI3K/Akt, BCL-2-family proteins, serpines, and HSP-90 among potential survival pathways. It does not identify SRC kinases or mitochondrial pathways as such defenses, and it describes the defenses as a hypothesis rather than establishing that all the listed pathways are upregulated in senescent cells. (LLM, conf=0.85)
- Partly supportedcites [57] Zhu, Y. et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of antiapoptotic factors. Aging Cell 15, 428–435 (2016). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says senescent cells resist apoptosis, potentially protecting them from their own inflammatory secretions, and reports upregulation of pro-survival pathways. The Results section on Bcl-2 family protein signatures (page unavailable) finds increased Bcl-xl and Bcl-2 in some, but not all, senescent cell types. Our copy does not establish upregulation of the other listed pathways—SRC, PI3K-AKT, HSP, and serpines—or show that every senescent cell with a proapoptotic SASP survives by these mechanisms. (LLM, conf=0.85)
- Partly supportedcites [58] Gasek, N. S., Kuchel, G. A., Kirkland, J. L. & Xu, M. Strategies for targeting senescent cells in human disease. Nat. Aging 1, 870–879 (2021). sourceExperimental — accuracy not yet measured
The Cellular Senescence section says senescent cells avoid apoptosis by upregulating pro-survival pathways. The Modulating SCAPs section discusses Src kinase inhibition, PI3K/Akt, BCL-2-family proteins, mitochondrial apoptotic signaling and HSP90. The cited copy does not identify serpines as one of these pathways or specifically describe survival of cells with a proapoptotic SASP in a cytotoxic microenvironment; the SASP section instead discusses inflammatory effects and resistance to immune-mediated clearance. Page numbers are unavailable in our copy. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This sterile inflammatory state can provoke dysfunction of neighboring and distant non-senescent cells, such as progenitor cells, contributing to impaired tissue function and reduced regenerative capacity18,21,24,26,34.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > Adverse impacts of persistent, proapoptotic SASP-expressing senescent cells.
What the sources say
- Partly supportedcites [18] Dungan, C. M. et al. Senolytic treatment rescues blunted muscle hypertrophy in old mice. Geroscience https://doi.org/10.1007/s11357-022-00542-2 (2022). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says senescent cells secrete pro-inflammatory factors that can disrupt muscle growth, and the Discussion links persistent senescent cells in old muscle with blunted growth. Our copy does not establish dysfunction of distant non-senescent cells or progenitor cells, or a resulting reduction in regenerative capacity. (LLM, conf=0.82)
- Partly supportedcites [21] Farr, J. N. et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat. Med. 23, 1072–1079 (2017). sourceExperimental — accuracy not yet measured
The paper’s Abstract says the inflammatory senescence-associated secretory phenotype has harmful paracrine and systemic effects and can cause tissue dysfunction. It also reports that senescent-cell-conditioned medium impaired osteoblast mineralization and altered osteoclast progenitor survival. It does not establish reduced regenerative capacity or show that progenitor cells themselves become dysfunctional. (LLM, conf=0.83)
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Introduction describes a pro-inflammatory senescence-associated secretory phenotype that contributes to local and systemic dysfunction. The Results report senescence in recipients’ own cells and inflammatory markers in distant muscle after senescent-cell transplantation, alongside impaired physical function. Our copy does not show that the affected recipient cells were progenitors or that their regenerative capacity was reduced; the paper used progenitors as transplanted cells. (LLM, conf=0.85)
- Supportedcites [26] Lewis-McDougall, F. C. et al. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell 18, e12931 (2019). source
The introduction (p. 2) describes the senescence-associated secretory phenotype as pro-inflammatory and having harmful effects both locally and systemically. The Abstract (p. 2) reports that factors secreted by senescent cardiac progenitor cells induce senescence in otherwise healthy progenitors; the discussion (p. 13) says the cardiac SASP impairs remaining non-senescent progenitors and limits myocardial regeneration. (LLM, conf=0.90)
- Supportedcites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). source
The Cellular senescence section describes a pro-inflammatory secretory phenotype that can cause stem and progenitor-cell dysfunction and tissue and systemic dysfunction. It also says deleterious senescent cells can spread senescence to normal cells even at a distance. Together, these passages support the claim about effects on nearby and distant cells and impaired tissue function and regeneration; the paper does not use the exact phrase “sterile inflammatory state.” Page numbers are unavailable in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- It may state two separate claims as one. 63
- The quote only partly states this claim. 1
- Probably not a substantial claim. 15
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The Geroscience Hypothesis holds that these pillars of aging, including cellular senescence, tend to progress in concert and may be root-cause contributors to the pathophysiology of multiple diseases”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Partly supportedcites [3] Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014). sourceExperimental — accuracy not yet measured
“The Pillars of Aging” section describes the seven pillars as highly intertwined processes that promote aging, and the introduction presents aging as a common driver of chronic disease. The paper also discusses cellular senescence and its potential adverse effects. It does not establish that the pillars progress together over time or that cellular senescence itself is a root-cause contributor to multiple diseases; no page numbers are available in our copy. (LLM, conf=0.82)
- Supportedcites [15] Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013). source
The Conclusions and Perspectives section says the hallmarks co-occur during aging and are interconnected; it identifies cellular senescence as a hallmark that can promote aging when excessive. The Abstract links aging-related deterioration to major diseases, supporting the sentence’s qualified claim that these processes may contribute to multiple diseases. The paper does not use the name “Geroscience Hypothesis,” but it presents the underlying account. (LLM, conf=0.87)
- Partly supportedcites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) identifies cellular senescence as a pillar of aging and says that targeting fundamental aging mechanisms can improve health span and resilience. The Abstract (page unavailable) links senescent-cell accumulation to loss of resilience and predisposition to many diseases. Neither passage says that the pillars of aging progress in concert, so that part of the attributed claim is unsupported. (LLM, conf=0.86)
- Partly supportedcites [17] Hadley, E. C., Kuchel, G. A., Newman, A. B. & Workshop Speakers and Participants. Report: NIA workshop on measures of physiologic resiliencies in human aging. J. Gerontol. A Biol. Sci. Med. Sci. 72, 980–990 (2017). sourceExperimental — accuracy not yet measured
The “Influence of Biologic Aging Mechanisms on Resilience” section identifies cellular senescence as a mechanism that could affect several types of resilience, and “Mechanistic Studies” says aging mechanisms may influence a wide variety of outcomes. Our copy does not say that the pillars of aging progress in concert or establish them as root-cause contributors to multiple diseases. (LLM, conf=0.84)
- Partly supportedcites [18] Dungan, C. M. et al. Senolytic treatment rescues blunted muscle hypertrophy in old mice. Geroscience https://doi.org/10.1007/s11357-022-00542-2 (2022). sourceExperimental — accuracy not yet measured
The Introduction links cellular senescence to age-related anabolic resistance in skeletal muscle, and the Discussion reports that reducing senescent cells enhances muscle growth in old mice. The paper does not state the broader Geroscience Hypothesis that pillars of aging progress together or contribute to the pathophysiology of multiple diseases (searched: “Geroscience Hypothesis,” “pillars of aging,” and “multiple diseases”). (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“After the first reports of senolytic drugs (agents that selectively eliminate senescent cells) in 2015 (ref. 14), promising results from preclinical studies have facilitated progression to early-phase clinical trials evaluating the safety and efficacy of senolytics, some of which have now been published (Table 1).”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). source
The citation is attached to the first reports of senolytic drugs in 2015, not to the later clinical-trial statement. This 2015 paper describes the identification of drugs that selectively kill senescent cells and calls dasatinib and quercetin prototype senolytic agents (Abstract; Discussion). (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Preclinical results in animal models predict human clinical outcomes for senolytic interventions.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Once senescent cell burden surpasses this threshold, continuing increases in proapoptotic/pro-inflammatory senescent cell burden may contribute to tissue destruction and hence development or progression of multiple diseases and age-related disorders (Table 2) as well as immune dysregulation, further amplifying senescent cell accumulation in a feed-forward loop36,38,62.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > Adverse impacts of persistent, proapoptotic SASP-expressing senescent cells.
What the sources say
- Partly supportedcites [36] Lagnado, A. et al. Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. EMBO J. 40, e106048 (2021). sourceExperimental — accuracy not yet measured
The Introduction links chronic exposure to the senescence-associated inflammatory response with age-associated tissue dysfunction. Results §5 proposes a vicious cycle in the liver: senescent cells recruit neutrophils, which may amplify senescence. The paper does not establish a burden threshold or support the broader claim of immune dysregulation and progression of multiple diseases through that loop; no page numbers are available in our copy. (LLM, conf=0.86)
- Partly supportedcites [38] Yousefzadeh, M. J. et al. An aged immune system drives senescence and ageing of solid organs. Nature 594, 100–105 (2021). sourceExperimental — accuracy not yet measured
The Abstract describes senescent cells as pro-inflammatory and tissue damaging and links them to age-related diseases. The “Rapamycin rejuvenates immune cells” section reports that immune-cell senescence impairs immunity and drives senescence in solid organs. Neither passage establishes a burden threshold, describes these cells as proapoptotic, or identifies the claimed feed-forward loop of accumulation; page numbers are not available in our copy. (LLM, conf=0.87)
- Supportedcites [62] Prata, L., Ovsyannikova, I. G., Tchkonia, T. & Kirkland, J. L. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin. Immunol. 40, 101275 (2018). source
In “Which comes first, immune system dysfunction or SC accumulation?” (page unavailable), the paper proposes that senescent cells can accumulate further when their abundance exceeds an immune-clearance threshold. “The SASP” describes chronic tissue damage and the spread of senescence, while the abstract says senescent cells can impede immune responses. The paper presents these links as possibilities, consistent with the claim’s hedged wording. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the other 30–70% of senescent cells, the SASP appears to comprise growth and other regenerative factors, potentially causing less apoptosis, tissue destruction and fibrosis than proapoptotic, pro-inflammatory senescent cells and can even contribute to tissue repair (for example, through the growth factors VEGF-A and PDGF-AA)61,65.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > The senescence-associated secretory phenotype.
What the sources say
- Partly supportedcites [61] Tripathi, U., Misra, A., Tchkonia, T. & Kirkland, J. L. Impact of senescent cell subtypes on tissue dysfunction and repair: importance and research questions. Mech. Ageing Dev. 198, 111548 (2021). sourceExperimental — accuracy not yet measured
In “Anti-apoptotic defenses vary among senescent cells” (page unavailable), the paper estimates that deleterious cells may comprise 30–70% of senescent cells and says the remaining helper cells release fewer pro-apoptotic factors and might aid wound healing through PDGF-AA. “Type of inducers” (page unavailable) also describes VEGF secretion by senescent fibroblasts, but does not identify those fibroblasts as helper cells. The paper does not specifically say that helper cells cause less fibrosis than deleterious cells. (LLM, conf=0.86)
- Partly supportedcites [65] Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports that senescent cells accelerate cutaneous wound healing through PDGF-AA secretion and help restrain fibrosis. The Results (page unavailable) also report increased VEGF mRNA in wounds, but do not establish VEGF-A as a repair mechanism. The paper does not support the 30–70% estimate or the comparison involving less apoptosis and tissue destruction. (LLM, conf=0.89)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By understanding and targeting cellular senescence and the other pillars of aging, rather than targeting individual diseases that are downstream of fundamental aging processes, it is conceivable that multimorbidity could be reduced and healthspan increased, with realization of substantial societal and economic benefits4,6.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Partly supportedcites [4] Scott, A. J., Ellison, M. & Sinclair, D. A. The economic value of targeting aging. Nat. Aging 1, 616–623 (2021). sourceExperimental — accuracy not yet measured
The Conclusion says delaying aging could affect many diseases, improve health and longevity, and yield large economic gains compared with treating specific diseases. The Results section likewise links targeting aging to age-related comorbidities and longer healthy life. The paper takes an economic rather than biological perspective, however, and these passages do not establish the claim specifically about targeting cellular senescence and other aging pillars. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [6] Tchkonia, T., Palmer, A. K. & Kirkland, J. L. New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 106, e1481–e1487 (2021). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Preclinical results in animal models predict human clinical outcomes for senolytic interventions.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“If senescent cells are present transiently, beneficial functions of both the proapoptotic and pro-growth types of SASP can orchestrate tissue remodeling”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > The senescence-associated secretory phenotype.
What the sources say
- Not checked — no full text of the sourcecites [10] Munoz-Espin, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482–496 (2014). source
- Could not verifycites [11] Suvakov, S. et al. Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies. EBioMedicine 70, 103536 (2021). sourceExperimental — accuracy not yet measured
The Introduction says physiological senescence prevents proliferation of damaged cells, and the Discussion says senescence is critical for embryogenesis. Neither passage addresses transient senescent cells, proapoptotic or pro-growth SASP, or SASP-driven tissue remodeling. Searches for tissue remodeling, parturition, and immune-cell clearance found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.76)
- Partly supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [61] Tripathi, U., Misra, A., Tchkonia, T. & Kirkland, J. L. Impact of senescent cell subtypes on tissue dysfunction and repair: importance and research questions. Mech. Ageing Dev. 198, 111548 (2021). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [62] Prata, L., Ovsyannikova, I. G., Tchkonia, T. & Kirkland, J. L. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin. Immunol. 40, 101275 (2018). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [65] Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, if a threshold burden of senescent cells is exceeded, senescent cells can accumulate, perhaps because proapoptotic SASP-expressing senescent cells induce paracrine and endocrine spread of senescence at a rate exceeding immune clearance of preexisting and newly formed senescent cells24,62”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > Adverse impacts of persistent, proapoptotic SASP-expressing senescent cells.
What the sources say
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Results report increased senescence markers in recipients’ own cells after transplantation and findings consistent with spread to distant tissues; they also say the SASP may induce senescence spreading in vivo. The Introduction says senescent-cell burden increases with aging. Our copy does not establish a threshold burden, identify proapoptotic SASP-expressing cells as the cause, or compare the rate of spread with immune clearance. (LLM, conf=0.86)
- Supportedcites [62] Prata, L., Ovsyannikova, I. G., Tchkonia, T. & Kirkland, J. L. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin. Immunol. 40, 101275 (2018). source
The section “Which comes first, immune system dysfunction or SC accumulation?” states that senescent-cell abundance would need to exceed an immune-clearance threshold to accumulate further, and that SASP can spread senescence. “The SASP” describes effects on nearby and distant cells, while the Abstract describes the SASP as pro-apoptotic. The citing sentence presents the proposed mechanism as a possibility, consistent with the source’s framing. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In 30–70% of senescent cells, this SASP entails pro-inflammatory, proapoptotic and pro-fibrotic factors7,31,40,59–64, some of which can cause previously non-senescent cells to become senescent both locally and at a distance in an endocrine manner24,39,47.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > The senescence-associated secretory phenotype.
What the sources say
- Partly supportedcites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). sourceExperimental — accuracy not yet measured
The Abstract describes the SASP as pro-inflammatory and tissue-destructive, section 4 calls it pro-apoptotic, and section 6 says it appears to contribute to pulmonary fibrosis. Our copy does not give the 30–70% figure or say that SASP factors induce senescence in previously non-senescent cells locally or at a distance through endocrine action. (LLM, conf=0.87)
- Partly supportedcites [31] Iske, J. et al. Senolytics prevent mtDNA-induced inflammation and promote the survival of aged organs following transplantation. Nat. Commun. 11, 4289 (2020). sourceExperimental — accuracy not yet measured
The Introduction identifies pro-inflammatory cytokines as part of the SASP, and the Discussion says the SASP induces senescence locally and systemically. Neither passage establishes the 30–70% figure or describes SASP factors as proapoptotic or pro-fibrotic; the paper also does not specify an endocrine mechanism. The supplied copy gives no page numbers for these sections. (LLM, conf=0.86)
- Partly supportedcites [40] Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). sourceExperimental — accuracy not yet measured
The paper defines paracrine senescence as senescence induced by a primary senescent cell’s SASP (Box 1; page unavailable), and describes inflammatory and tissue-remodeling SASP factors (DNA damage response; page unavailable). It does not give the 30–70% figure or establish that SASP factors induce senescence at a distance through endocrine action; its example of a distal effect concerns cancer-cell proliferation. (LLM, conf=0.87)
- Partly supportedcites [59] Basisty, N. et al. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol. 18, e3000599 (2020). sourceExperimental — accuracy not yet measured
The Introduction describes SASP cytokines, chemokines, growth factors, and proteases that initiate inflammation in nearby cells, and the Results identify inflammatory factors in the secretome. But the paper does not say that 30–70% of senescent cells have a SASP containing proapoptotic and pro-fibrotic factors. Its reported percentages concern other measures, such as the proportion of cells induced to senesce by a treatment. The endocrine-senescence clause carries separate citations in the citing sentence. (LLM, conf=0.84)
- Partly supportedcites [60] Coppe, J. P., Desprez, P. Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010). sourceExperimental — accuracy not yet measured
The ‘Soluble Signaling Factors’ section (page not available) describes inflammatory SASP cytokines and a secreted factor that can induce senescence and apoptosis in neighboring cells. It does not establish that 30–70% of senescent cells have a SASP containing all three stated classes of factors, particularly pro-fibrotic factors. The local-and-distant endocrine claim has a separate citation group in the citing sentence and is not assessed against this source. (LLM, conf=0.85)
- Partly supportedcites [61] Tripathi, U., Misra, A., Tchkonia, T. & Kirkland, J. L. Impact of senescent cell subtypes on tissue dysfunction and repair: importance and research questions. Mech. Ageing Dev. 198, 111548 (2021). sourceExperimental — accuracy not yet measured
The “Anti-apoptotic defenses vary among senescent cells” section says pro-inflammatory and pro-apoptotic D-senescent cells may comprise about 30–70% of senescent cells, based on unpublished observations; it does not include pro-fibrotic factors in that description. The “Endocrine and paracrine impact of the SASP” section says SASP factors can spread senescence to previously normal cells locally and in distant organs. The claim is therefore supported in part, but states the tentative percentage more firmly and adds an unsupported pro-fibrotic component. (LLM, conf=0.86)
- Partly supportedcites [62] Prata, L., Ovsyannikova, I. G., Tchkonia, T. & Kirkland, J. L. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin. Immunol. 40, 101275 (2018). sourceExperimental — accuracy not yet measured
The SASP section says senescent cells can affect nearby and distant cells through the SASP, including by spreading senescence, and describes inflammatory SASP factors. It does not give the 30–70% figure or characterize the factors as proapoptotic and pro-fibrotic. Although it mentions effects on endocrine function, it does not specify endocrine action as the mechanism by which senescence spreads at a distance. (LLM, conf=0.86)
- Partly supportedcites [63] Justice, J. N. et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine 40, 554–563 (2019). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) describes the SASP as containing pro-fibrotic factors and contributing to a pro-inflammatory response; it also says senescent cells release pro-apoptotic factors as part of their SASP. Our copy does not support the cited clause’s 30–70% figure. The claim about inducing senescence locally and at a distance has separate citations in the citing sentence and is not attributed to this source. (LLM, conf=0.86)
- Partly supportedcites [64] Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966–972 (2013). sourceExperimental — accuracy not yet measured
The SASP and Figure 2 passages describe inflammatory SASP factors and suggest that senescence can spread to neighboring cells. They do not establish the 30–70% figure, characterize SASP factors as proapoptotic or pro-fibrotic, or show that they induce senescence at a distance through endocrine action; the paper also frames spreading senescence as a possibility needing further investigation. Page numbers were not available in our copy. (LLM, conf=0.86)
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report increased senescence markers in distant muscle after senescent-cell transplantation, and the Discussion proposes spread of senescence locally and to distant tissues. This supports the locally-and-at-a-distance part of the claim, but the paper presents spreading as a possible explanation rather than establishing that specific SASP factors cause it through endocrine action. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“cell types such as activated macrophages, which may not be classically senescent, can have high p16INK4a expression100, but are not targeted by D + Q24.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Supportedcites [100] Hall, B. M. et al. p16Ink4a and senescence-associated beta-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging 9, 1867–1884 (2017). source
The Introduction says macrophages can express p16Ink4a in response to physiological stimuli, distinctly from cellular senescence. The Discussion likewise describes p16Ink4a-positive macrophages that lack definitive properties of senescence. The D + Q statement has a separate citation and is not attributed to this source. (LLM, conf=0.93)
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Results report that D+Q did not significantly reduce p16INK4A-positive macrophages in human adipose-tissue explants, and the Discussion describes little direct effect on macrophages. The paper does not specifically test activated macrophages, and its acute explant findings do not establish that D+Q never targets them. (LLM, conf=0.82)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“in commonly used preclinical models, senescence is abolished by means of p16INK4a-based or p21CIP1/WAF1-based genetic clearance and this senescence-targeting approach acts through mechanisms that are distinct from first-generation, SCAP-targeting small-molecule senolytics; as a result, there appear to be differences in the types of senescent cells targeted.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [100] Hall, B. M. et al. p16Ink4a and senescence-associated beta-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging 9, 1867–1884 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“senescent mesenchymal embryonic fibroblasts from Ercc1−/− mice and bone marrow mesenchymal progenitors from old mice are not eliminated by either D or Q alone, but are eliminated by the combination of these agents14.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). sourceExperimental — accuracy not yet measured
The Results section, “Dasatinib and quercetin reduce senescent cells in vivo” (page unavailable), reports that the combination significantly reduced senescent mouse embryonic fibroblasts compared with either drug alone. It also reports that quercetin alone significantly reduced senescent bone marrow-derived mesenchymal stem cells, contrary to the claim that neither drug alone eliminates them. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Each of these approaches eliminates senescent cells, although in some cases, activated macrophages and other non-senescent cell types are also affected96–99.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [96] Amor, C. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127–132 (2020). sourceExperimental — accuracy not yet measured
The paper reports that uPAR-directed CAR T cells eliminate senescent cells and that supratherapeutic doses cause macrophage accumulation and activation (Abstract, page unavailable). It also notes uPAR expression in monocytes, macrophages, neutrophils and bronchial epithelium, but does not show that those naturally occurring non-senescent cells were eliminated or otherwise affected by treatment. Its killing experiment used non-senescent leukemia cells engineered to express uPAR. (LLM, conf=0.82)
- Partly supportedcites [97] Yoshida, S. et al. The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice. Nat. Commun. 11, 2482 (2020). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report reduced accumulation of senescent T cells in vaccinated mice and show that vaccine-induced antibodies killed LPS-stimulated macrophage cells in a complement-dependent assay. The paper does not establish effects on other non-senescent cell types, so it supports only part of the sentence attributed to this source. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [98] Suda, M. et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat. Aging 1, 1117–1126 (2021). source
- Partly supportedcites [99] Poblocka, M. et al. Targeted clearance of senescent cells using an antibody-drug conjugate against a specific membrane marker. Sci. Rep. 11, 20358 (2021). sourceExperimental — accuracy not yet measured
The Introduction and Results report that the antibody–drug conjugate kills senescent cells. They do not report effects on activated macrophages or other non-senescent cell types; the Introduction instead says the tested treatment showed no toxicity to proliferating cells. The Discussion raises off-target effects as a possibility requiring further study, not an observed result. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“HSP90 prevents proteasomal degradation of AKT, hence inhibiting HSP90 disables pro-survival signaling through this SCAP node and results in elimination of some senescent cell types54.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [54] Fuhrmann-Stroissnigg, H. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8, 422 (2017). sourceExperimental — accuracy not yet measured
The Results section reports that HSP90 inhibition reduced active p-AKT and led to apoptosis in senescent cells; the Discussion says downregulating this survival pathway may contribute to senolytic activity. The paper does not establish that HSP90 prevents proteasomal degradation of AKT: it reports that total AKT was unchanged by the inhibitor. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Certain cell surface proteins tend to be more highly expressed by senescent cells than most other cell types, which prompted development of engineered chimeric antigen receptor (CAR) T cells, vaccines and antibody–drug conjugates targeting these cell surface markers.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [96] Amor, C. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127–132 (2020). sourceExperimental — accuracy not yet measured
The paper’s Abstract reports that surface proteins are upregulated in senescent cells and that the authors developed uPAR-targeting CAR T cells. It does not report the development of vaccines or antibody–drug conjugates targeting those markers, so those parts of the attributed claim are unsupported. Page numbers are unavailable in our copy. (LLM, conf=0.90)
- Partly supportedcites [97] Yoshida, S. et al. The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice. Nat. Commun. 11, 2482 (2020). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes a vaccine targeting CD153 on senescent T cells, supporting the vaccine example. The paper does not report CAR T cells or antibody–drug conjugates, and it does not establish that senescent cells generally express these surface proteins more highly than most other cell types. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [98] Suda, M. et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat. Aging 1, 1117–1126 (2021). source
- Partly supportedcites [99] Poblocka, M. et al. Targeted clearance of senescent cells using an antibody-drug conjugate against a specific membrane marker. Sci. Rep. 11, 20358 (2021). sourceExperimental — accuracy not yet measured
The Introduction describes membrane proteins upregulated in senescent cells, and the Introduction and Discussion describe developing an antibody–drug conjugate targeting one of those markers. The cited paper does not support the claim that these markers prompted development of CAR T cells or vaccines; those approaches are not described in the passages retrieved for those terms. The paper also notes that senescent-cell markers are not specific and universal. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In some types of senescent cells, SCAPs can be redundant, so that targeting a single SCAP may not eliminate such cells—but combination treatment targeting multiple SCAPS may be effective.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says dasatinib and quercetin generally work better together than individually and proposes drug combinations to target anti-apoptotic networks. The Results (page unavailable) report that the combination reduced senescent mouse embryonic fibroblasts more than either drug alone. The paper does not establish that redundancy among SCAPs is why targeting a single pathway may fail. (LLM, conf=0.84)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, work to develop senolytics began before genetic models of senescent cell clearance were published and did not depend on those models34,56.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). sourceExperimental — accuracy not yet measured
The “Discovery of senolytic drugs” section says the authors began trying to remove senescent cells in 2005, prompted by a 2004 study, and describes a later drug-discovery strategy based on apoptosis resistance. This supports an independent starting point, but the passages do not establish when genetic clearance models were published, so the claimed publication order is not verified by this source. (LLM, conf=0.82)
- Supportedcites [56] Wissler Gerdes, E. O., Zhu, Y., Tchkonia, T. & Kirkland, J. L. Discovery, development, and future application of senolytics: theories and predictions. FEBS J. 287, 2418–2427 (2020). sourceExperimental — accuracy not yet measured
The discovery of senolytics section (Fig. 1 caption; page not available) explicitly says development began before and independently of making or studying INK-ATTAC mice, a genetic model used to eliminate senescent cells. The section also says senolytic discovery did not depend on findings from those mice. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The SASP of senescent cells is not static; it can change over time78–80 and varies depending on the type of cells that became senescent and how senescence was induced16,44,59,60,81.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways > Adverse impacts of persistent, proapoptotic SASP-expressing senescent cells.
What the sources say
- Supportedcites [78] Hoare, M. et al. NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat. Cell Biol. 18, 979–992 (2016). sourceExperimental — accuracy not yet measured
The Results section on dynamic NOTCH1 signalling reports that SASP components change at different stages of senescence: TGF-β ligands rise transiently, while IL-6 and IL-8 rise mainly at full senescence. This supports the temporal-change point to which this source is cited. The Results section on enforced NOTCH1 activation also describes different secretory profiles under different methods of inducing senescence. (LLM, conf=0.91)
- Supportedcites [79] De Cecco, M. et al. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566, 73–78 (2019). sourceExperimental — accuracy not yet measured
The time-dependent clause is the part of the citing sentence attributed to this paper. Extended Data Figure 3 reports changes in SASP-related gene expression between early and late senescence, and the ‘Consequences of L1 activation’ section distinguishes early from late SASP markers. The cell-type and induction clause has a separate citation group. (LLM, conf=0.90)
- Could not verifycites [80] Zhao, Y. et al. Transposon-triggered innate immune response confers cancer resistance to the blind mole rat. Nat. Immunol. 22, 1219–1230 (2021). sourceExperimental — accuracy not yet measured
The citation is attached to the claim that SASP varies by senescent cell type and mode of induction. The Results section and Extended Data Fig. 1 report SASP activation in over-proliferating blind mole rat cells, but do not compare SASP across senescent cell types or induction methods. I searched the indexed copy for those comparisons; no passage establishes the attributed variation. (LLM, conf=0.70)
- Supportedcites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). sourceExperimental — accuracy not yet measured
The section “SnCs have an altered response to SARS-CoV-2 spike protein” reports different inflammatory profiles among senescent cell types and compares cells made senescent through replication versus radiation. In the citing sentence, separate citations accompany the claim about change over time; this source supports the cell-type and induction-method portion. (LLM, conf=0.88)
- Partly supportedcites [44] Tripathi, U. et al. SARS-CoV-2 causes senescence in human cells and exacerbates the senescence-associated secretory phenotype through TLR-3. Aging 13, 21838–21854 (2021). sourceExperimental — accuracy not yet measured
The Results section shows that viral exposure and TLR-3 activation amplify SASP factors in senescent human cells, supporting the point that the SASP is not fixed. The cited paper does not establish the broader claim that SASP composition varies according to cell type or how senescence was induced. In the citing sentence, the separate claim about change over time is attached to other citations. (LLM, conf=0.82)
- Supportedcites [59] Basisty, N. et al. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol. 18, e3000599 (2020). sourceExperimental — accuracy not yet measured
The Introduction describes the SASP as dynamic and dependent on cell type and senescence inducer. The Results also report distinct secretory profiles across inducing stimuli. In the citing sentence, the change-over-time clause has a separate set of citations; this source supports the cell-type and inducer clause. (LLM, conf=0.92)
- Supportedcites [60] Coppe, J. P., Desprez, P. Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010). sourceExperimental — accuracy not yet measured
The “Specificity of the Senescence-Associated Secretory Phenotype” section describes the SASP developing over time after senescence induction. It also reports variation in SASP composition by cell type and by the means of inducing senescence. Page numbers were not provided in our copy. (LLM, conf=0.93)
- Could not verifycites [81] Decout, A., Katz, J. D., Venkatraman, S. & Ablasser, A. The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nat. Rev. Immunol. 21, 548–569 (2021). sourceExperimental — accuracy not yet measured
The ‘cGAS–STING in senescence and ageing’ section describes SASP secretion and a role for cGAS–STING across multiple types of senescent cells. It does not say that the SASP changes over time or varies by cell type or how senescence was induced; searches for those distinctions found no supporting passage. (LLM, conf=0.74)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This is in agreement with a recent report showing that the removal of senescent cells expressing high levels of p16INK4a can lead to fibrosis in mice101, whereas small-molecule senolytics appear to reduce fibrosis in several mouse tissues22,71,73,75,102.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Supportedcites [101] Grosse, L. et al. Defined p16high senescent cell types are indispensable for mouse healthspan. Cell Metab. 32, 87–99 (2020). source
The citation to this paper supports the first clause, about removing p16-high senescent cells; the senolytics clause has separate citations. In “Continuous removal of p16 High senescent cells in vivo results in liver and systemic peri-vascular fibrosis” (page not provided), the paper reports increased liver and peri-vascular collagen deposition after removal of these cells in mice. Its acute-removal section also reports fibrosis. (LLM, conf=0.94)
- Supportedcites [22] Moncsek, A. et al. Targeting senescent cholangiocytes and activated fibroblasts with B cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2−/−) mice. Hepatology 67, 247–259 (2018). source
The cited paper supports the senolytics clause: its Results report that the small-molecule Bcl-xL inhibitor A-1331852 reduced senescent cholangiocytes and liver fibrosis in Mdr2−/− mice. It serves as one example within the group of citations for reduced fibrosis, not as the source for the preceding claim that removing p16-high cells can cause fibrosis. (LLM, conf=0.90)
- Partly supportedcites [71] Schafer, M. J. et al. Cellular senescence mediates fibrotic pulmonary disease. Nat. Commun. 8, 14532 (2017). sourceExperimental — accuracy not yet measured
The Results section (‘Senescent cell clearance mitigates fibrotic lung disease’; page unavailable) reports that the small-molecule senolytic dasatinib plus quercetin improved lung function in bleomycin-injured mice. But reductions in lung fibrosis on histopathology did not reach statistical significance, and this paper does not establish reduced fibrosis across several mouse tissues. The separate claim that removing p16-expressing cells can cause fibrosis is attached to citation 101, not this source. (LLM, conf=0.88)
- Partly supportedcites [73] Cavalcante, M. B. et al. Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice. Aging 12, 2711–2722 (2020). sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe anti-fibrotic effects of dasatinib and quercetin in several tissues, supporting the general point attributed to this source. But this paper’s own mouse experiment found no significant reduction in uterine fibrosis with treatment (Results; treatment effect P = 0.503). This citation does not support the clause about removing p16INK4a-high cells, which is attached to a different reference. (LLM, conf=0.85)
- Could not verifycites [75] Ogrodnik, M. et al. Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun. 8, 15691 (2017). sourceExperimental — accuracy not yet measured
Citation 102 is attached to the claim that small-molecule senolytics reduce fibrosis in several mouse tissues. The Results section, “Senescent cell clearance decreases liver fat accumulation” (page unavailable), reports that dasatinib plus quercetin reduced hepatic fat deposition, not fibrosis. Searches for fibrosis and fibrotic outcomes found no passage in our copy reporting the claimed reduction. (LLM, conf=0.78)
- Not checked — no full text of the sourcecites [102] Kim, S. R. et al. Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin. Transl. Res. 213, 112–123 (2019). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“forkhead box O4 (FOXO4) retains p53 in the nucleus, so peptides interfering with this interaction can lead to p53-mediated apoptosis in some types of senescent cells87.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Supportedcites [87] Baar, M. P. et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169, 132–147 (2017). source
In the Results section on FOXO4-DRI and p53 release, the paper reports that the peptide competes with FOXO4 for p53 binding and causes active p53 to leave the nucleus. The subsequent Results section reports p53-dependent, caspase-mediated apoptosis in senescent cells, supporting the claim's qualified wording. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“senescent human fat cell progenitors (preadipocytes or mesenchymal stromal cells) are sensitive to D but not Q or F, while senescent human umbilical vein endothelial cells are sensitive to Q or F but not D14.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [14] Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015). sourceExperimental — accuracy not yet measured
In Results (‘Candidate senolytic drugs in vitro’; page unavailable), dasatinib preferentially killed senescent human preadipocytes and was much less effective on HUVECs, while quercetin preferentially killed senescent HUVECs and was less effective on preadipocytes. The paper does not support the claim about fisetin, and ‘less effective’ does not establish the categorical ‘not sensitive’ claims. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“these genetic models are of limited use to assess the translational potential of senolytic agents—but are useful for mechanistic insights nonetheless.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Partly supportedcites [100] Hall, B. M. et al. p16Ink4a and senescence-associated beta-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging 9, 1867–1884 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A recent study implicated cellular senescence and the beneficial effects of senolytics for Down syndrome (trisomy 21)13.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Supportedcites [13] Meharena, H. S. et al. Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors. Cell Stem Cell 29, 116–130 (2022). source
The Discussion reports senescence-associated features in trisomy 21 neural progenitor cells and says senolytic treatment restored their migratory and proliferative capacity. It presents senolytics as a potential therapeutic avenue for Down syndrome, consistent with the citing sentence’s cautious wording. (LLM, conf=0.92)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The antidiabetic drug metformin, which, among other activities, inhibits the SASP, alleviates several age-related conditions and chronic diseases110–114.”
§ Cellular senescence and senolytics: the path to the clinic > SASP inhibitors
What the sources say
- Not checked — no full text of the sourcecites [110] Novelle, M. G., Ali, A., Dieguez, C., Bernier, M. & de Cabo, R. Metformin: a hopeful promise in aging research. Cold Spring Harb. Perspect. Med. 6, a025932 (2016). source
- Partly supportedcites [111] Hansel, C. et al. Metformin protects against radiation-induced acute effects by limiting senescence of bronchial-epithelial cells. Int. J. Mol. Sci. 22, 7064 (2021). sourceExperimental — accuracy not yet measured
The Introduction (page not available) says metformin inhibits the SASP and has been shown to alleviate aging-associated cellular senescence. It describes alleviating aging-related diseased phenotypes as a potential benefit of SASP inhibitors, but does not establish that metformin alleviates several age-related conditions and chronic diseases. (LLM, conf=0.85)
- Partly supportedcites [112] Deschenes-Simard, X. et al. Circumventing senescence is associated with stem cell properties and metformin sensitivity. Aging Cell 18, e12889 (2019). sourceExperimental — accuracy not yet measured
The Results section, ‘Metformin targets reprogrammed pancreatic cancer cells’ (page unavailable), reports reduced tumor-sphere formation after metformin treatment. The Discussion, ‘The transition from PanIN’ (page unavailable), reports delayed pancreatic tumorigenesis in mice. Neither passage shows that metformin inhibits the SASP or establishes that it alleviates several age-related conditions and chronic diseases. (LLM, conf=0.85)
- Partly supportedcites [113] Kulkarni, A. S., Gubbi, S. & Barzilai, N. Benefits of metformin in attenuating the hallmarks of aging. Cell Metab. 32, 15–30 (2020). sourceExperimental — accuracy not yet measured
The section on cellular senescence reports that metformin suppresses SASP in several age-associated settings, but also says its effect is context-dependent and can increase SASP-related expression in some cancer settings. The Introduction reports clinical benefits for diabetes and cardiovascular disease, while evidence for several other age-related diseases is described largely as associations with lower incidence; the unqualified claim that metformin alleviates them overstates that evidence. (LLM, conf=0.85)
- Partly supportedcites [114] Fang, J. et al. Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7. Aging Cell 17, e12765 (2018). sourceExperimental — accuracy not yet measured
The Introduction reports that metformin can alleviate various age-associated disorders, including cardiovascular disease, cancer, and cognitive decline. The Results and Discussion report reduced cellular senescence with metformin, but the passages found do not establish that it inhibits the SASP specifically. Page numbers were not available in our copy. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the advantages of D, Q or F over some other senolytics are their brief half-lives (4, 11 or 3–4 h, respectively, in humans) and rapid elimination120–122.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
What the sources say
- Not checked — no full text of the sourcecites [120] Christopher, L. J. et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab. Dispos. 36, 1357–1364 (2008). source
- Not checked — no full text of the sourcecites [121] Graefe, E. U. et al. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharm. 41, 492–499 (2001). source
- Partly supportedcites [122] Touil, Y. S. et al. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. Biochem. Pharmacol. 82, 1731–1739 (2011). sourceExperimental — accuracy not yet measured
Section 3.1 (p. 13) reports a 3.12-hour terminal half-life for fisetin, but this was measured in mice after intraperitoneal dosing, not in humans. The Discussion (p. 18) emphasizes species differences in elimination. This paper does not establish a human half-life or show that rapid elimination is an advantage over other senolytics; the dasatinib and quercetin figures are not attributed to this source specifically. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Oral D + Q reduces this neuroinflammation, increases markers of neurogenesis, reduces gliosis and alleviates anxiety in obese mice33.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [33] Ogrodnik, M. et al. Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Cell Metab. 29, 1061–1077 (2019). sourceExperimental — accuracy not yet measured
The Methods report oral gavage of D+Q in obese db/db mice. The Results report improved anxiety-like behavior, increased neurogenesis markers, and reduced lipid-laden, senescent glial cells after D+Q. They also report reduced circulating inflammatory factors, but do not show that D+Q reduced neuroinflammation in the brain or gliosis generally. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
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In the paper
“In mouse models of diet-induced obesity, reducing the burden of senescent cells in adipose tissue by administering D + Q attenuates adipose tissue inflammation, alleviates metabolic dysfunction, and restores the capacity of preadipocytes to differentiate into functional, mature, insulin-responsive fat cells25.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [25] Palmer, A. K. et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell 18, e12950 (2019). sourceExperimental — accuracy not yet measured
The Results sections on senescent-cell clearance and adipogenic potential report reduced adipose senescence, improved glucose control and insulin sensitivity, and higher adipogenic gene expression after D + Q in diet-induced obese mice. The inflammation findings in diet-induced obese mice chiefly follow genetic senescent-cell clearance; the D + Q macrophage-homing experiment used db/db mice. The paper also suggests that progenitors can differentiate into insulin-responsive fat cells, but does not directly demonstrate that D + Q restores differentiation into functional, mature insulin-responsive cells. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Rapamycin and its analogs (so-called ‘rapalogs’) suppress the SASP by inhibiting mTOR and appear to extend healthspan and lifespan in mice105,108,109.”
§ Cellular senescence and senolytics: the path to the clinic > SASP inhibitors
What the sources say
- Partly supportedcites [105] Lamming, D. W., Ye, L., Sabatini, D. M. & Baur, J. A. Rapalogs and mTOR inhibitors as anti-aging therapeutics. J. Clin. Invest. 123, 980–989 (2013). sourceExperimental — accuracy not yet measured
The review’s “Effects of rapamycin on longevity” section (page unavailable) reports that rapamycin extends mouse lifespan, and it describes delays in several age-related changes in mice. But our copy does not report suppression of the SASP, nor does it establish that rapalogs extend mouse healthspan or lifespan; its conclusion calls for further testing of mTOR-targeting strategies. (LLM, conf=0.88)
- Partly supportedcites [108] Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009). sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that rapamycin inhibits the mTOR pathway and extends median and maximal lifespan in genetically heterogeneous mice. It does not report SASP suppression, effects of rapalogs, or an extension of healthspan; it says that whether mTOR inhibition alters other aspects of ageing remains to be tested. (LLM, conf=0.90)
- Partly supportedcites [109] Neff, F. et al. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Invest. 123, 3272–3291 (2013). sourceExperimental — accuracy not yet measured
The Results (p. 2) confirm that rapamycin extended lifespan in mice, and the Introduction (p. 1) identifies it as an mTOR inhibitor. But the paper does not establish SASP suppression or effects of rapalogs, and its Discussion (p. 13) reports that many aging phenotypes were not improved; it therefore does not support a broad healthspan benefit. (LLM, conf=0.90)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“D + Q treatment of either old donor mice, the organs harvested from the old donors before transplantation, or the recipients, led to decreased senescent cell burden and increased survival of recipient mice – so that outcomes resembled those observed in mice receiving a transplant from a young donor31.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [31] Iske, J. et al. Senolytics prevent mtDNA-induced inflammation and promote the survival of aged organs following transplantation. Nat. Commun. 11, 4289 (2020). sourceExperimental — accuracy not yet measured
The Results sections on senolytics report that D+Q reduced senescent-cell markers in old mice and that treating old donors prolonged cardiac graft survival; with recipient CTLA4-Ig treatment, graft survival was comparable to that of hearts from young donors (pages unavailable). The paper does not report D+Q treatment of harvested organs or transplant recipients, and the survival outcome measured was graft survival, not recipient-mouse survival. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This may be a result of inhibiting SASP-mediated spread of senescence, thereby allowing the innate and adaptive immune system to further reduce senescent cell burden, consistent with the Unitary Theory (Fig. 2).”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
What the sources say
- Partly supportedcites [116] Mannick, J. B. et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci. Transl. Med. 10, eaaq1564 (2018). sourceExperimental — accuracy not yet measured
The passage labeled Abstract (page not provided) reports reduced infections for a year after six weeks of mTOR-inhibitor treatment and suggests persistent improvement in immune function. It also discusses changes in immune responses, but does not link the prolonged effect to SASP-mediated spread of senescence or a reduction in senescent cell burden. (LLM, conf=0.85)
- Partly supportedcites [117] Bitto, A. et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife 5, e16351 (2016). sourceExperimental — accuracy not yet measured
The Results report that rapamycin-fed mice retained better grip strength and Rotarod performance 90 days after treatment ended, supporting a prolonged effect. The paper does not attribute that effect to inhibition of SASP-mediated senescence spread, immune clearance of senescent cells, or the Unitary Theory. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The study suggested that apoptosis of mesenchymal stromal cells is required for their therapeutic effects, possibly by means of downstream immunosuppressive effects of apoptotic processes123.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
What the sources say
- Supportedcites [123] Pang, S. H. M. et al. Mesenchymal stromal cell apoptosis is required for their therapeutic function. Nat. Commun. 12, 6495 (2021). source
The Introduction states that MSC apoptosis and subsequent efferocytosis are required for their full immunosuppressive effects in vivo. The Discussion explains that clearance of apoptotic MSCs alters macrophage responses and produces immunosuppression. Page numbers are not provided in our copy. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In age-related osteoporosis linked to senescent-like osteocytes and bone marrow cells in mice, D + Q reduced development of bone-resorbing osteoclasts, while increasing differentiated bone-forming osteoblasts, with restoration of bone mass21.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [21] Farr, J. N. et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat. Med. 23, 1072–1079 (2017). sourceExperimental — accuracy not yet measured
The D+Q results (Abstract; page unavailable in our copy) report improved bone microarchitecture and fewer osteoclasts in aged mice. Osteoblast numbers increased on the endocortical surface, but did not change in trabecular bone. The reported osteoclast counts do not establish that D+Q reduced osteoclast development. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Whereas transplanting senescent cells decreases healthspan and lifespan in preclinical models, eliminating transplanted or endogenous senescent cells increases healthspan, thereby fulfilling Koch’s postulates for causality24,124.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Results report that senescent-cell transplantation caused physical dysfunction and increased mortality in mice. The Discussion reports that senolytics alleviated transplantation-induced dysfunction and that clearing senescent cells improved physical function and remaining lifespan in old mice. It describes this evidence as satisfying a *modified set* of Koch’s postulates, rather than Koch’s postulates without qualification. (LLM, conf=0.82)
- Partly supportedcites [124] Yousefzadeh, M. J. et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36, 18–28 (2018). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) reports that injecting senescent cells causes frailty and decreased survival in mice, while clearing senescent cells from aging mice has therapeutic benefits. The Results (page unavailable) report improved age-related pathology and longer lifespan after fisetin treatment. Our copy does not state that eliminating transplanted cells improves healthspan or that these findings fulfill Koch’s postulates. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
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In the paper
“in a mouse model of idiopathic pulmonary fibrosis (IPF), D + Q treatment improved lung compliance and reduced frailty71.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [71] Schafer, M. J. et al. Cellular senescence mediates fibrotic pulmonary disease. Nat. Commun. 8, 14532 (2017). sourceExperimental — accuracy not yet measured
The Results section, “Senescent cell clearance mitigates fibrotic lung disease” (page unavailable), reports that D+Q limited the bleomycin-induced reduction in mouse lung compliance and improved weight retention and treadmill performance. These physical-health measures are consistent with reduced frailty, but the paper does not report a direct frailty assessment. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
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In the paper
“some SASP inhibitors can have agent-specific off-target effects, for example, rapamycin, which can cause nephrotoxicity, metabolic impairment and susceptibility to infections, at least at higher doses in mice109.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
What the sources say
- Partly supportedcites [109] Neff, F. et al. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Invest. 123, 3272–3291 (2013). sourceExperimental — accuracy not yet measured
The Figure 8 text (p. 12) reports considerable nephrotoxicity, impaired glucose tolerance, and hypercholesterolemia in rapamycin-treated mice. The paper does not establish increased susceptibility to infections from rapamycin or show that these adverse effects occur specifically at higher doses; its mention of infection concerns age-related immune dysfunction (p. 10). (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In livers of HFD-fed mice, oral D + Q reduces the burden of senescent hepatocytes and hepatic steatosis75.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Partly supportedcites [75] Ogrodnik, M. et al. Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun. 8, 15691 (2017). sourceExperimental — accuracy not yet measured
The Results (section “Senescent cell clearance decreases liver fat accumulation”; page unavailable) report that D+Q reduced senescence markers and liver fat in aged and db/db mice. In the high-fat-diet experiment, however, the treatment reported to reduce senescent hepatocyte markers and hepatic fat was AP, not D+Q. The Methods (Animals; page unavailable) specify oral gavage of D+Q for the db/db mice, so the claimed combination of oral D+Q and high-fat-fed mice is not supported. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the case of SASP inhibitors, continuous treatment is needed to maintain suppression of the SASP, although some agents, such as rapamycin, can have prolonged effects after a brief course of administration116,117.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
What the sources say
- Partly supportedcites [116] Mannick, J. B. et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci. Transl. Med. 10, eaaq1564 (2018). sourceExperimental — accuracy not yet measured
The discussion passage in our copy (labeled Abstract; page unavailable) reports fewer infections for a year after six weeks of BEZ235 or RAD001 plus BEZ235, and cites lifespan extension after 6–12 weeks of rapamycin in elderly mice. This supports prolonged effects after a short course, but the paper does not establish that those effects are SASP suppression or that continuous treatment is needed to maintain SASP suppression. (LLM, conf=0.87)
- Partly supportedcites [117] Bitto, A. et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife 5, e16351 (2016). sourceExperimental — accuracy not yet measured
The Results report that healthspan benefits in middle-aged mice persisted 90 days after a three-month rapamycin course, supporting the claim that brief treatment can have prolonged effects. The paper does not establish that continuous treatment is needed to maintain SASP suppression, or that the persistent effects measured were SASP suppression. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“senolytics can increase α-Klotho, which is geroprotective, neuroprotective and linked to healthspan in mice19.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Supportedcites [19] Zhu, Y. et al. Orally active, clinically translatable senolytics restore α-Klotho in mice and humans. EBioMedicine 77, 103912 (2022). source
The Results section reports that senolytic treatment increased α-Klotho in the urine, kidney, and brain of mice. The Introduction describes α-Klotho as geroprotective and links it to healthspan and cognitive function, noting enhanced cognition in mice overexpressing it. No page numbers are available in our copy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because side effects of senolytics in humans are not yet fully known, and to maximize benefit–risk ratios, the first clinical trials are underway in patients with serious health conditions, such as diabetic kidney disease, Alzheimer’s disease, frailty and IPF34.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions
What the sources say
- Supportedcites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). source
The Clinical trials section says that unknown short- and long-term side effects require a careful risk–benefit balance and that initial trials should focus on serious conditions. Table 3 in Strategies for translating agents targeting fundamental ageing processes into treatments lists trials for IPF, Alzheimer’s disease, diabetic chronic kidney disease, and frailty as recruiting; page numbers are unavailable in our copy. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The non-feminizing estrogen, 17α-estradiol, declines with aging in females and males and 17α-estradiol treatment extends healthspan and alleviates age-related metabolic dysfunction and inflammation in mice142.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Partly supportedcites [142] Stout, M. B. et al. 17α-estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. J. Gerontol. A Biol. Sci. Med. Sci. 72, 3–15 (2017). sourceExperimental — accuracy not yet measured
The Abstract and Discussion (page numbers unavailable) report improved metabolic and inflammatory measures in aged male mice and describe 17α-estradiol as a potential way to improve healthspan. They do not report that endogenous 17α-estradiol declines with age in either sex, or establish that treatment extends healthspan; the reported lifespan extension is limited to male mice. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Senescent cells can decrease NAD+ through SASP activation of the NAD-degrading enzyme CD38 on the surface of macrophages and, remarkably, senolytics partially restore tissue NAD+ levels139,140.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Partly supportedcites [139] Chini, C. C. S. et al. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. Nat. Metab. 2, 1284–1304 (2020). sourceExperimental — accuracy not yet measured
The Results section on SASP-induced CD38 reports that secretions from senescent cells increased CD38 activity in macrophages and lowered NAD+ in mouse white adipose tissue. The Results section on cellular senescence reports that clearing senescent cells partly restored NAD+ in that tissue, but the experiment used genetic ablation in INK-ATTAC mice, not a senolytic treatment. The Discussion also notes that NAD+ recovery was much greater in the liver. (LLM, conf=0.88)
- Partly supportedcites [140] Schultz, M. B. & Sinclair, D. A. Why NAD+ declines during aging: it’s destroyed. Cell Metab. 23, 965–966 (2016). sourceExperimental — accuracy not yet measured
The paper’s Abstract links rising CD38 activity during aging to declining NAD+ levels and reports that mice lacking CD38 retain higher NAD+ levels. It does not describe SASP activation of CD38 on macrophages or report that senolytics restore tissue NAD+; its discussion of inflammation as a possible trigger is speculative. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The timing, the particular senolytic agent used, and the age, sex, and other characteristics of the individual may impact effectiveness of senolytics24.”
§ Cellular senescence and senolytics: the path to the clinic > Systemic versus local administration
What the sources say
- Partly supportedcites [24] Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018). sourceExperimental — accuracy not yet measured
The Results section reports that D+Q was beneficial when given immediately or five weeks after senescent-cell transplantation, with comparable effects at both times. The Discussion considers optimized agents and says efficacy in tissues from older humans needs study. The paper does not establish that timing, choice of agent, age, sex, or other individual characteristics change senolytic effectiveness; in particular, it reports benefits in both male and female mice. (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
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In the paper
“Exercise may delay senescent cell formation and reduce inflammation, frailty and chronic disease onset in mice136,137.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Partly supportedcites [136] Duggal, N. A., Niemiro, G., Harridge, S. D. R., Simpson, R. J. & Lord, J. M. Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity? Nat. Rev. Immunol. 19, 563–572 (2019). sourceExperimental — accuracy not yet measured
In “Physical activity as a therapy” (page not specified), the review reports that exercise prevented senescent-cell accumulation in the adipose tissue of mice with diet-induced obesity. It links senescent cells to inflammation, but attributes prevention of age-related disease in mice to removal of those cells, not to exercise. The cited passage does not establish that exercise reduces frailty or chronic disease onset in mice. (LLM, conf=0.88)
- Partly supportedcites [137] Schafer, M. J. et al. Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 65, 1606–1615 (2016). sourceExperimental — accuracy not yet measured
The Results and Discussion (page numbers unavailable) report that exercise reduced diet-induced senescence markers and inflammatory signaling in the visceral fat of mice, while improving physical and metabolic measures. The paper does not show that exercise reduced frailty or delayed the onset of chronic diseases in these mice; those effects extend beyond the outcomes studied. (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Metformin, resveratrol and rapalogs (agents related to rapamycin) are SASP inhibitors and appear to impact some of the same basic processes as caloric restriction or exercise110,138.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Not checked — no full text of the sourcecites [110] Novelle, M. G., Ali, A., Dieguez, C., Bernier, M. & de Cabo, R. Metformin: a hopeful promise in aging research. Cold Spring Harb. Perspect. Med. 6, a025932 (2016). source
- Partly supportedcites [138] Baur, J. A. et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337–342 (2006). sourceExperimental — accuracy not yet measured
The pathway comparison (labeled Abstract in our copy; page unavailable) reports that resveratrol and caloric restriction altered several pathways in the same direction. It does not establish that resveratrol is a SASP inhibitor or address whether metformin and rapalogs share those effects, and the cited passages do not compare resveratrol with exercise. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Transiently disabling SCAP pathways results in apoptosis of the senescent cells with a tissue-destructive SASP, while non-senescent cells or those senescent cells with a pro-growth, non-apoptotic SASP remain viable (U. Tripathi, S.C., L.G.P.L. Prata, T.T. and J.L.K., unpublished data).”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Not matchedcites U. Tripathi, S.C., L.G.P.L. Prata, T.T. and J.L.K., unpublished data
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescent cells accumulate during aging and at pathogenic sites of multiple disorders and diseases.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescent cells can arise throughout the lifespan”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One such process is cellular senescence, which entails a state of cell cycle arrest in response to damaging stimuli.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
In the paper
“The Unitary Theory of Fundamental Aging Mechanisms builds on the Geroscience Hypothesis by positing that interventions targeting any one fundamental mechanism may target the others6.”
§ Cellular senescence and senolytics: the path to the clinic > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Tchkonia, T., Palmer, A. K. & Kirkland, J. L. New horizons: novel approaches to enhance healthspan through targeting cellular senescence and related aging mechanisms. J. Clin. Endocrinol. Metab. 106, e1481–e1487 (2021). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescent cells, which are in a state of essentially irreversible cell cycle arrest but remain viable”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“can accumulate with aging, especially in more frail individuals, and at pathogenic sites of multiple disorders and diseases in experimental animals and humans across the lifespan.”
§ Cellular senescence and senolytics: the path to the clinic > Cellular senescence: mechanisms and pathways
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Due to ruptured lysosomal membranes, at least some senescent cells depend on glutamine metabolism as a pH-buffering system, inhibition of which renders them vulnerable to apoptosis95.”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Not checked — no full text of the sourcecites [95] Johmura, Y. et al. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371, 265–270 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
In the paper
“a potential new application of senolytics may entail ex vivo perfusion of organs from older donors that are currently being discarded because of increased risk of organ failure or allograft rejection, potentially offsetting shortages of organs for transplantation125.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Not checked — no full text of the sourcecites [125] Tullius, S. G. & Rabb, H. Improving the supply and quality of deceased-donor organs for transplantation. N. Engl. J. Med. 378, 1920–1929 (2018). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Obesity also leads to accumulation of senescent cells near the third ventricles of the murine brain, together with development of neuropsychiatric dysfunction, particularly anxiety, which results from altered function of the limbic system situated near the third ventricles.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the first-generation senolytics target the underlying cause of detrimental SASP factor production by eliminating those senescent cells that release proapoptotic factors.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senolytics cause SASP-expressing senescent cells to undergo apoptosis, and such senescent cells are present at sites of dysfunction.”
§ Cellular senescence and senolytics: the path to the clinic > Advantages and disadvantages of senolytics versus SASP inhibitors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“HFD-induced senescent mouse kidney cells are linked to renal fibrosis and functional impairment; Q treatment reduces senescent cell burden and SASP marker expression, alleviates renal fibrosis and improves kidney function102.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
What the sources say
- Not checked — no full text of the sourcecites [102] Kim, S. R. et al. Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin. Transl. Res. 213, 112–123 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These genetic models have been useful in pinpointing those cells expressing particular senescence-linked markers (for example, p16INK4a or p21CIP1/WAF1) and as complementary tools in senolytic proof-of-concept studies (Table 2).”
§ Cellular senescence and senolytics: the path to the clinic > Discovery and development of senolytic drugs
What the sources say
- Not matchedcites Table 2
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“High-fat diets (HFDs) and obesity result in senescent cell accumulation and lead to impaired function of multiple organs.”
§ Cellular senescence and senolytics: the path to the clinic > Senolytics in preclinical models
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“once systemic senolytic treatment has reduced overall senescent cell burden to below a threshold, the immune system might clear remaining senescent cells, including those resistant to that particular senolytic.”
§ Cellular senescence and senolytics: the path to the clinic > Systemic versus local administration
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such ICD codes would facilitate regulatory approvals, recording of conditions linked to fundamental aging processes in hospital and insurance records, epidemiological studies, physician and hospital reimbursement and engagement of the pharmaceutical industry.”
§ Cellular senescence and senolytics: the path to the clinic > Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“In an open-label phase 1 pilot study in 9 patients with diabetic kidney disease, a 3-d course of oral D + Q was sufficient to decrease adipose tissue senescent cell burden, inflammation, fibrosis and circulating SASP factors for at least 11 d after the last dose of senolytics, indicating target engagement and suggesting that an intermittent dosing regimen may be effective in humans48.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions
What the sources say
- Not checked — no full text of the sourcecites [48] Hickson, L. J. et al. Corrigendum to ‘Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease’ EBioMedicine 47 (2019) 446–456. EBioMedicine 52, 102595 (2020). source
hedgeddirectn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“if the Unitary hypothesis is correct, they may contribute less-than-additive effects because fundamental aging mechanisms are tightly interconnected.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- The authors state this as an assumption: The Unitary Theory/hypothesis that fundamental aging mechanisms are tightly interconnected is correct.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ongoing efforts are underway to identify and define biomarkers of senescent cell accumulation (senescence biomarkers) and destruction of senescent cells during senolytic treatment (senolysis biomarkers) that meet requirements of regulatory authorities.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Biomarkers of senescent cell burden and senolysis: gerodiagnostics.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A more promising strategy could be to combine geroscience with disease-specific interventions.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“TAME will test if metformin delays the appearance of a second age-related disorder in patients who already have one such disorder; it will not be a trial including completely healthy older adults115.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
What the sources say
- Not matchedcites [115] American Federation for Aging Research. Targeting the biology of aging. Ushering a new era of interventions. https://www.afar.org/tame-trial (2022).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In our hands and others, nutlin-3a does not show or shows only weak senolytic activity and, in some cases, can even induce cellular senescence95,130.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions
What the sources say
- Not checked — no full text of the sourcecites [95] Johmura, Y. et al. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371, 265–270 (2021). source
- Not checked — no full text of the sourcecites [130] Efeyan, A. et al. Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast origin. Cancer Res. 67, 7350–7357 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The lack of WHO International Classification of Disease (ICD) codes for multimorbidity, sarcopenia, healthspan or the geriatric syndromes represents a barrier to clinical development.”
§ Cellular senescence and senolytics: the path to the clinic > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This approach could both enhance sensitivity and reduce ‘denominator effects’; for example, creatinine is often used as a dominator for urine analytes, introducing the confounding variable of muscle mass, upon which creatinine levels depend.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Biomarkers of senescent cell burden and senolysis: gerodiagnostics.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“F may be beneficial but D detrimental in healthy young female mice that have not yet accumulated many senescent cells129.”
§ Cellular senescence and senolytics: the path to the clinic > Systemic versus local administration
What the sources say
- Not checked — no full text of the sourcecites [129] Fang, Y. et al. Sexual dimorphic responses of C57BL/6 mice to fisetin or dasatinib and quercetin cocktail oral treatment. Preprint at bioRxiv https://doi.org/10.1101/2021.11.08.467509 (2021). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“consistent with the Unitary Theory, interventions targeting the different fundamental aging mechanisms appear to alleviate aging phenotypes, delay, prevent or treat multiple diseases, and extend healthspan in preclinical models.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“According to the threshold theory of cellular senescence, senescent cells can be present without clinical manifestations but, if their abundance exceeds a threshold, senescent cell burden can increase further and contribute to development of local and systemic dysfunction and multiple diseases (Fig. 2).”
§ Cellular senescence and senolytics: the path to the clinic > Systemic versus local administration
What the sources say
- Not matchedcites Fig. 2
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Promising results of senolytics in preclinical models suggest therapeutic and preventive opportunities for delaying multimorbidity and increasing healthspan.”
§ Cellular senescence and senolytics: the path to the clinic > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the failure of this clinical trial seems related to the particular agent administered, which may not have been a fully effective senolytic.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clinical studies of geroscience interventions targeting the other pillars of aging are currently underway or being planned.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Sirtuins facilitate DNA damage repair, partially relying on oxidized NAD+ to do so.”
§ Cellular senescence and senolytics: the path to the clinic > Clinical trials and future directions > Clinical trajectory for the next decade.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
Preclinical results in animal models predict human clinical outcomes for senolytic interventions.
“promising results from preclinical studies have facilitated progression to early-phase clinical trials evaluating the safety and efficacy of senolytics”
The paper relies on this without support.
CAR T cell therapy is expensive, individually formulated, can cause graft-versus-host disease, and requires prolonged immunosuppression.
“Furthermore, CAR T cell therapy is expensive, generally has to be specifically formulated for each individual being treated, and can lead to graft versus host disease, necessitating prolonged immunosuppressive therapy with all its attendant risks.”
The authors state this as an assumption.
The Unitary Theory/hypothesis that fundamental aging mechanisms are tightly interconnected is correct.
“if the Unitary hypothesis is correct, they may contribute less-than-additive effects because fundamental aging mechanisms are tightly interconnected.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genetic or pharmacological clearance of p16 positive cells in different tissues has shown efficacy in more than forty disease models, including models of neurodegenerative diseases.1”
From A pilot study of senolytics to improve cognition and mobility in older adults at risk for Alzheimer's disease (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The target specificity and toxicity to non-senescent cells is still a big hurdle for clinical applications of the current senolyitc treatments.14,15”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [15]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Inhibiting these SCAPs disrupts the survival machinery of SnCs, triggering their selective apoptosis while sparing normal cells in some contexts26,27”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [27]
In the citing paper
“The elimination of senescent cells has been observed to mitigate ageing associated events, such as inflammation, stem cell exhaustion, and mitochondrial dysfunction.537”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [537]
In the citing paper
“Currently, around 20 clinical trials of senotherapies are ongoing, two of which (NCT04785300 and NCT04685590) are evaluating the therapeutic efficacy of D+Q in individuals with MCI or AD.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [186]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“Zhang, B. et al. KDM4 orchestrates epigenomic remodeling of senescent cells and potentiates the senescence-associated secretory phenotype. Nat. Aging 1, 454–472 (2021).”
Cited work 10.1038/s43587-021-00063-1 · retracted 2024-10-31 · notice 10.1038/s43587-024-00749-2 · this paper published 2022-08
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
Cited work 10.1101/2020.08.03.235465 · retraction date not known · this paper published 2022-08
Citations
Cites
2 retracted
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Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
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Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Self-citation
Cited by
Sorted by citations
Items 901–1,000 of 1,072
Kawabata, S., Iijima, H., Kanemura, N., & Murata, K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-024-04666-8
“In recent years, senescent cell-depleting drugs (senolytic drugs) have been developed to address the various adverse effects of senescent cells through SASP, which have significantly improved aging-associated decline in tissue function [19–22].”
Vardon, A., Haston, S., Guiho, R., Carvahlo, D., Carter, R., Boult, J. K. R., Gharai, D., Santhakumar, D., Cloete, I., Gray, J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.20.629607
Chemical induction of cell senescence with iron-palladium nanoalloys for cancer therapy
Zhao, Y., Ji, X., Zheng, Y., Wang, H., Zhu, J., Li, Y., Geng, D., Ni, D., & Yin, B. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.159142
Evolutionary conserved reciprocal senescence and tumor suppressor signals limit lifetime cancerPreprint
Liu, L., Davis, S. A., Yusuff, S., Strange, A., Zhuang, Y., Vaddi, P. K., Flaherty, K., Jara, K., Kramer, J., Archer, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.28.630560 · Cited by 1
Eg5 Inhibitor SB743921 Causes p53-Dependent Cell Cycle Arrest, Senescence and Death in Tumor CellsPreprint
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The role of cardiovascular aging in heart failure
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Antiaging Interventions: Global Clinical Trials on Antiaging Treatments
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Cellular Senescence and Cardiovascular Aging
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Cellular Senescence and Cancer
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Molecular imaging for senescent cells-targeted therapeutics in aging and age-related diseases
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“In this context, senolytics is a new category of compounds shown to mitigate cellular senescence ( 55 ).”
Gene Therapy Against Age-Related Diseases
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Senescence And The Senescence Associated Secretory Phenotype In Salivary Hypofunction
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Research progress on histone modifications and anti-aging interventions
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Impact of viruses and retrotransposons on genetic instability and aging
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10th Anniversary of Biomedicines—Advances in Endothelial Dysfunction
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The effect of cellular senescence on hearing loss
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Organ Failure: Examples of Extracellular Matrix Involvement and Treatment
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Cellular Senescence in Multiple Sclerosis (MS)
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Nano-Transducers Composed of Lipids Visualize Population Doubling Levels of Cells
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“Recent remarkable successes with lipid-based nanoparticles in drug delivery systems [1] suggest, they could contribute to senolysis [2–4]: selectively eliminating senescent cells.”
In-Depth Exploration of Radiation-Induced Cell Death Mechanisms in Tumor
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“The current anti-aging strategies can be categorized into 3 categories: Senolytics target a series of signaling pathways of senescent cells and disrupt their anti-apoptotic mechanisms by using mainly small molecules that need repeated administration [177].”
Anti-aging strategies for dogs
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Senolytic Therapy as a Preventive Strategy for Low Back PainPreprint
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Targeting cellular senescence for cancer therapy
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Autophagy and Neuroinflammatory Pathways in Alzheimer’s Disease
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“While the accumulation of senescent cells with age can induce inflammation, it can also exert beneficial effects on other cells such as the secretion of growth factors [5].”
Exploring promising pharmaceutical candidates for antiaging
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Fliri, A. F. J., Sostek, R., & Kajiji, S. M. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1577844
Application of senescence reporter mouse models in panvascular diseases
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Additional file 1 of NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence
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Additional file 2 of NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence
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Tri des cellules sénescentes par cytométrie en flux
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“Cellular senescence is a protective response to accumulated stress or damage and plays a complex dual role in tumor biology 32, 33 .”
Pathogenetic markers of cellular senescence
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Pore-forming venoms as a senolytic strategy
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The Impact of Ageing on Fibrillar Collagens
Canty‐Laird, E. G., Gupta, H. S., & Birch, H. L. (2026) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-032-05273-5_12 · Cited by 1
Ostermann, P. N., Dinnendahl, R., Isensee, J., & Hucho, T. B. (2026) · Pain Research and Management · doi:10.64898/2026.01.20.700573
“Cellular senescence is an apoptosis-resistant state of irreversible cell cycle arrest induced by various stressors and associated with the development of a senescence-associated secretory phenotype (SASP) [7; 14].”
InfluentialOchiiwa, H., Wakasa, T., Kataoka, Y., Ando, K., Oki, E., Maehara, Y., Iimori, M., & Kitao, H. (2026) · Cancer Science · doi:10.1111/cas.70329 · Cited by 1
“Given that the selective elimination of senescent cells extends lifespan and prevents or alleviates age-associated diseases in mice [8, 9], senolytic drugs have been developed to target these cells [7, 10].”
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“Senolytics have distinct advantages over senomorphics: whereas seno-morphics suppress the SASP and require continuous administration to maintain this effect, senolytics eradicate the SASP source itself—the senescent cell—allow-ing treatment discontinuation once clearance is achieved [19].”
Lee, H. C., Haffner, M. P., Balog, S., Taladriz‐Blanco, P., Mroczek, A., Staudinger, S., Petri‐Fink, A., & Rothen‐Rutishauser, B. (2026) · Nanoscale · doi:10.1039/d5nr05035a
“19,20 Senolytic drugs, designed to eliminate these cells, have shown promise in addressing age-related diseases, 21,22 and interest is growing in using nanoparticles (NPs) to enhance these therapies further.”
Fan, Y., Wang, Z.-H., Zhang, X., Dong, Y., Liu, X., Luo, G., Yang, H., Li, H., Wang, Z., Tang, Q., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04138-2 · Cited by 1
“Senescent cells in certain tissues contribute to physiological remodeling and homeostasis, and non-targeted senolysis may inadvertently eliminate these beneficial populations, leading to adverse effects [24, 41–45].”
Dasatinib and Quercetin Senolytics for Health and Longevity
Salas-Venegas, V., Flores-Torres, R. P., Alarcón‐Aguilar, A., López‐Díazguerrero, N. E., & Königsberg, M. (2026) · Healthy ageing and longevity · doi:10.1007/978-3-032-11608-6_20
Therapeutic strategies targeting muscle stem cells in satellite cell-opathies
Garcia, P., Mokhtari, I., & Dumont, N. A. (2026) · Journal of Neuromuscular Diseases · doi:10.1177/22143602251414570
Yang, X., Chen, H., Wu, T., Ji, Z.-Y., Wang, Z.-W., Liu, Z.-L., Yang, J.-K., Zhao, Y., Zhou, M., & Wang, X.-B. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.117841
Transplanting ANXA1⁻ CD8⁺ Naïve T cells Delay Aging Through SenolysisPreprint
Wu, Y., Guo, S. Z., Zhang, F., Lou, F., Li, Y. Y., Sun, Y., Shen, Q., Zhao, L., Cai, X., Wang, Z., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.21.707223
SENOLYTICS – A DISCOVERY THAT COULD TRANSFORM THE COURSE OF AGING AND CHRONIC DISEASES
Kania, K., Bobiński, M., Wieczorek, Z., Skowron, W., Bartol, J., Sosińska, A., Rajczyk, J., Wiczuk-Wiczewska, M., Szymczak, A., & Lepich, T. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.1(49).2026.5128
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Myocardial Aging: Cellular Mechanisms and Therapeutic Perspectives
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“For instance, dasatinib and quercetin, senolytics currently undergoing clinical trials, work this way [244, 246].”
Liu, J., Ren, X., Wang, H., Yang, D., Yan, Y., & Xu, Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1748788
Microglial senescence and senolytic drugs
Ben-Azu, B., Sabbah, S., Awogbindin, I. O., Chidebe, E. O., Oritsemuelebi, B., Patel, D., Frenkel, D., & Tremblay, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27340-7.00010-3
Regulation of Aging by the Epigenome
Oyabu, M., & Kamei, Y. (2025) · KAGAKU TO SEIBUTSU · doi:10.1271/kagakutoseibutsu.63.123
Taherian, S. F., Shakery, A., Eslamian, G., Tadayon, N., Ardehali, S. H., Zand, H., Ghorbani, A., Shimi, G., Sohouli, M. H., & Behtaj, D. (2026) · Nutrire · doi:10.1186/s41110-026-00440-z
Ventricular assist device unloading reverses microvascular senescence in single ventricle disease
Li, X., Turaga, D., Zhao, Y., Tsai, C.-R., Li, R. G., Morikawa, Y., Tadros, H. J. J., Samee, M. A. H., Adachi, I. A., & Martin, J. F. (2026) · Nature Cardiovascular Research · doi:10.1038/s44161-026-00790-x · Cited by 2
“A similar conceptual paradigm has been observed in paracrine senescence in skeletal muscle, which inhibits regeneration and induces inflammation and muscle aging 42,43 .”
Plasminogen Activator Inhibitor 1, Cell Senescence, and Aging-Related Diseases
Liu, R.-M., & Nakamya, M. F. (2026) · Cells · doi:10.3390/cells15060551 · Cited by 1
“Emerging evidence indicates that cellular senescence contributes importantly to the neu-ropathophysiology of AD and PD [42,154,226–239].”
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Multiomic single-cell perturbation screens reveal critical lncRNA regulators of senescence
Zhu, S., Ying, S., Cai, D., Ren, Y., Wang, L., Qi, Z., Gorbunova, V., & Han, J. J. (2026) · Nature Aging · doi:10.1038/s43587-026-01100-7 · Cited by 1
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The Role of α-Tubulin Acetyltransferase (αTAT1) in Glioblastoma Cellular Responses to Radiotherapy
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Lee, K.-S., Numakawa, T., Horita, C., Ishitsuka, Y., Motoyama, K., Takeo, T., & Era, T. (2026) · GeroScience · doi:10.1007/s11357-026-02244-5
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“Cells responding to various stressors can induce senescence, involving cell cycle arrest, chromatin rearrangement, morphological changes, metabolic shifts toward glycolysis, and release of senescence-associated secretory phenotype (SASP) factors [23, 24].”
Clofoctol as a novel senolytic drug eliminating therapy-induced senescent glioma cells
Zhang, Y. Y., Wang, Z., Wang, Y., Li, E., Wu, F., Hou, L., Yin, B., Qiang, B., Han, W., & Peng, X. (2026) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdag102
Cell-specific vulnerabilities and adaptations in atrial aging
Braun, A. M. T., Lang, A., & Wagner, J. U. G. (2026) · Cardiovascular Research · doi:10.1093/cvr/cvag081
Prostate cancer and cellular senescence: focusing on the tumor microenvironment
Zhang, D., Yan, J., Jin, Q., Lv, X., & Ma, Y. (2026) · ONCOLOGIE · doi:10.1515/oncologie-2026-0025
“By selectively inducing apoptosis in senescent cells, they eliminate pro-tumorigenic populations and reduce persistent SASP signaling that promotes in fl ammation and therapeutic resistance [99].”
InfluentialQuercetin and Fisetin activate circadian clock via RORα and inhibit adipocyte growthPreprint
Xiong, X., Pangemanan, J., Kiperman, T., Sun, Z., Paul, A., Yechoor, V. K., & Ma, K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.28.721484
“Quercetin and fisetin are known agents that promote cellular senescence, a class of molecules that are defined as senolytics [57].”
Reversing PROTAC-induced ASH2L degradation reactivates proliferation in senescent cellsPreprint
Müller, J., Barsoum, M., Bussmann, P., Mabrouk, M. H. E., Sayadi-Boroujeni, R., Vllaho, A.-M., Stenzel, A. T., Vogt, L., Kießling, P., Kuppe, C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.02.722411
Fang, B., Zeng, D., Duan, Z., Gao, B., Zhu, T., He, X., Xu, L., Liu, X., He, Q., Huang, L., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-71205-5
“Whereas many studies have emphasized signaling-driven, largely static measures of collagen synthesis and degradation 107 – 111 , pathway cross-talk can generate unintended effects 112,113 .”
Li, D., Onodera, S., Yu, Q., & Zhou, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27094080
“By secreting an array of pro-inflammatory cytokines, chemokines and other signaling molecules, senescent cells in tissues profoundly influence the surrounding environment and critically contribute to tissue inflammation, degeneration and dysfunction [29–31].”
Senolytic effects of first and second generation BCL-xL/BCL-2 dual degraders
Berezhnaya, E. S., & Savustyanenko, A. V. (2026) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2026-14-2-136-146
de Almeida, A. J. P. O., Pontes, L. V. D. S., Júnior, J. F. D. S., Soares, E. M. C., dos Santos, A. C., Gonçalves, T. A. F., Feitosa, M. S. D. A., Veras, R. C., Barbosa‐Filho, J. M., Lesniewski, L. A., et al. (2026) · Molecules · doi:10.3390/molecules31101614
“Therefore, the development of therapies that aim to reduce the deleterious consequences of senescence burden is necessary for the clinic [34,35].”
FoxO signaling in regulated cell death and its therapeutic implications in inflammation
Zhang, K., Mo, C., Wen, B., Ma, Z., & Ma, D. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116830 · Cited by 1
Insights into lower reproductive tract aging: Mechanisms and perspectives
Wang, R., Liang, C., Li, Y., & Zhu, L. C. (2026) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2026.112192
Dissecting out the unexpected effects of SGLT2 inhibitors on human aging
Katsuumi, G., & Minamino, T. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag207 · Cited by 1
Blomquist, S. A., Kelly, G., D’Adamo, C. R., Han, C., Parker, H., Adães, S., Gardner, C. R., Ardagh, A., Ramer, S., & Scuba, W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104406 · Cited by 1
“It has also been noted that continuous SASP repression can inhibit pathways necessary for the maintenance of tissue homeostasis and immune surveillance [31–33], highlighting the importance of balancing senotherapeutic efficacy with preservation of essential physiologic functions.”
Multicellular senescence programs in the aged heart
Bultot, L., Tsurudome, N., Kumazaki, E., & Shimizu, I. (2026) · Journal of Molecular and Cellular Cardiology Plus · doi:10.1016/j.jmccpl.2026.100852
“The dasatinib – quercetin combination therapy (D + Q) is well known to mediate senolysis, and several clinical trials are underway to test its effect across multiple disorders [119,120].”
Bat-Inspired Longevity: Immune Damage Management and Nutritional Modulation for Healthy Aging
Park, S., & Daily, J. W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104467
“Centenarians maintain efficient efferocytosis through elevated NK cells and CMV-specific cytotoxic T lymphocytes (CTLs) with senolytic capacity, preventing SASP-mediated inflammation [62,90,100,115].”
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Yu, Y., He, Y., Wang, Y., Wu, C., Zhou, R., Chen, F., & Ma, W. (2026) · The FASEB Journal · doi:10.1096/fj.202601360r
“However, long-term safety, optimal dosing period, and exact efficacy in humans remain key issues that need to be addressed [250, 266].”
Shao, Q., Chen, D., Shao, W., & Ye, Q. (2026) · Research · doi:10.34133/research.1326 · Cited by 1
Metadata
- Authors
- Chaib, S., Tchkonia, T., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Kirkland, James L.
- Venue
- Nature Medicine
- Published
- 2022-08
- Volume
- 28
- Issue
- 8
- Pages
- 1556-1568
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC9599677
- OpenAlex
- W4292488030
- Semantic Scholar
- 6088d989a0da63569aa5a064559c21fe6e5792a9
- Cited by
- 1,134
- References
- 242
- Citations by year
- 2026: 255 · 2025: 335 · 2024: 324 · 2023: 195 · 2022: 25
- FWCI
- 25.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R37AG13925, R33AG61456, R01AG072301, R01AG61414, P01AG62413, UH3AG56933)
- the Connor Fund, Robert J. and Theresa W. Ryan, and the Noaber Foundation.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senolytics, senescence-associated secretory phenotype, aging, age-related diseases, clinical trials, drug repurposing
- MeSH terms
- Senotherapeutics, Aging, Humans, Cellular Senescence, Cell Cycle Checkpoints
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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