Cellular senescence and senolytics: the path to the clinic

In the paper

“fundamental aging processes can operate even before conception, for example, in the context of aged oocytes linked to Down syndrome12,13.”

What the sources say

• Supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

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.”

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 supported

  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)

  cites [3] Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014). sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• ?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
• Supported

  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)

  cites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). source

In the paper

“Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases.”

What the sources say

• Supported

  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)

  cites [3] Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014). source
• Supported

  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)

  cites [15] Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013). source
• Partly supported

  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)

  cites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

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.”

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 supported

  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)

  cites [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
• Partly supported

  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)

  cites [9] Ness, K. K. et al. Frailty in childhood cancer survivors. Cancer 121, 1540–1547 (2015). sourceExperimental — accuracy not yet measured
• ?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 supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

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”

What the sources say

• Partly supported

  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)

  cites [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
• Supported

  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)

  cites [40] Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). source
• ?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 supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Supported

  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)

  cites [52] Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019). source
• ?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

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.”

What the sources say

• Supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [40] Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [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
• ?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 supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

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.”

What the sources say

• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

In the paper

“This proapoptotic SASP can have detrimental effects both locally and systemically due to senescent cell accumulation and persistence24.”

What the sources say

• Partly supported

  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)

  cites [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

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.”

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 supported

  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)

  cites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). sourceExperimental — accuracy not yet measured
• ?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 supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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

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.”

What the sources say

• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Partly supported

  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)

  cites [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
• Supported

  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)

  cites [26] Lewis-McDougall, F. C. et al. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell 18, e12931 (2019). source
• Supported

  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)

  cites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). source

In the paper

“N can cause thrombocytopenia and neutropenia, even after brief exposures57,88–91”

What the sources say

• Partly supported

  The Discussion (page unavailable) says navitoclax can affect platelets, causing bleeding, and can cause neutropenia. It does not specifically identify thrombocytopenia or say these effects occur after brief exposure; the short exposures described in the Results concern senescent-cell experiments, not these adverse effects. (LLM, conf=0.86)

  cites [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
• Partly supported

  The paper’s concluding discussion (indexed under Abstract; page unavailable) identifies thrombocytopenia and neutropenia as common, transient toxicities of ABT263 treatment in patients. It does not say that either occurs after brief exposure. The Online Methods describe short treatment cycles in mice but do not link those cycles to these toxicities. (LLM, conf=0.87)

  cites [88] Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Patients and Toxicity; page unavailable) report both thrombocytopenia and neutropenia during navitoclax treatment. The Results (Pharmacodynamic Effects; page unavailable) describe a platelet decline after a single dose, supporting the brief-exposure qualifier for thrombocytopenia. Neutropenia, however, tended to occur in later treatment cycles, so the paper does not support that qualifier for both toxicities. (LLM, conf=0.89)

  cites [89] Wilson, W. H. et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 11, 1149–1159 (2010). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page not specified) identifies Navitoclax as ABT-263, reports rapid platelet loss, and lists neutropenia among side effects in some patients. It does not establish that both thrombocytopenia and neutropenia occur after brief exposure. (LLM, conf=0.88)

  cites [90] Afreen, S. et al. BCL-XL expression is essential for human erythropoiesis and engraftment of hematopoietic stem cells. Cell Death Dis. 11, 8 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  Section 2 identifies navitoclax as ABT-263 and states that it can cause thrombocytopenia in mice and humans. The passages found do not establish that ABT-263 causes neutropenia or that either effect occurs after brief exposure. (LLM, conf=0.88)

  cites [91] Josefsson, E. C., Vainchenker, W. & James, C. Regulation of platelet production and lifespan: role of Bcl-xL and potential implications for human platelet diseases. Int. J. Mol. Sci. 21, 7591 (2020). sourceExperimental — accuracy not yet measured

In the paper

“These include retrotransposable elements (for example, LINE-1), cytosolic mitochondrial DNA, or circular DNA—all of which can activate the cytosolic DNA-sensing (cGAS)-STING pathway, triggering the expression of pro-inflammatory genes79–81.”

What the sources say

• Partly supported

  The Consequences of L1 activation section reports that suppressing cGAS or STING inhibited the interferon response and reduced pro-inflammatory SASP gene expression in late-senescent cells. The paper also mentions mitochondrial DNA as a possible source of cytoplasmic DNA, but does not establish the claimed pathway for mitochondrial DNA or address circular DNA. Its Extended Data examine cells at 12–16 weeks of senescence. (LLM, conf=0.87)

  cites [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
• Partly supported

  The Results section (‘RTEs form Cytoplasmic RNA/DNA Hybrids and induce cGAS-STING’; page not provided) links LINE-1 and other retrotransposons to cGAS-STING activation and IFNB1/SASP gene expression in blind mole rat cells. The cited paper does not establish the same pathway for cytosolic mitochondrial DNA or circular DNA, or a weeks-to-months delay after senescence induction. (LLM, conf=0.88)

  cites [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
• Partly supported

  The sections on cell-intrinsic genomic and mitochondrial DNA describe LINE-1-derived DNA and cytosolic mitochondrial DNA activating cGAS–STING. The senescence and ageing section links cGAS–STING activity to inflammatory secretions from senescent cells. Our copy does not establish circular DNA as one of these triggers or specify that pro-inflammatory genes are induced weeks or months after senescence induction (pages unavailable). (LLM, conf=0.86)

  cites [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

In the paper

“Persistent senescent cells appear to be highly responsive to extracellular cues, such as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), which can exacerbate the proapoptotic, pro-inflammatory qualities of the SASP16.”

What the sources say

• Partly supported

  The Discussion (page unavailable) says senescent cells are primed to respond to PAMPs by producing more inflammatory SASP factors, supporting the PAMP and pro-inflammatory parts of the claim. The passages do not establish a response to DAMPs or describe the amplified SASP as proapoptotic. (LLM, conf=0.87)

  cites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). sourceExperimental — accuracy not yet measured

In the paper

“certain HSP90 inhibiting drugs, such as geldanamycin, are senolytic against particular senescent cell types.”

What the sources say

• Supported

  The Results section ('HSP90 inhibitors as a novel class of senolytics') identifies geldanamycin as an HSP90 inhibitor that selectively reduced the viability of senescent MEFs at 1 μM. The Discussion also explicitly calls geldanamycin a senolytic compound. The claim is limited to particular senescent cell types, so it does not imply that geldanamycin works on every type. (LLM, conf=0.93)

  cites [54] Fuhrmann-Stroissnigg, H. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8, 422 (2017). source

In the paper

“In some cases, senolytic compounds that target a single SCAP node, such as the BCL-2 pathway inhibitors, N (ABT-263), A1331852 or A1155463, tend to induce apoptosis in a restricted range of senescent cell types57,86.”

What the sources say

• Partly supported

  The Introduction and Results report that navitoclax (ABT-263) induces apoptosis in some senescent cell types but is not senolytic in human primary preadipocytes. Our copy does not address A1331852 or A1155463, so it does not establish the claim for those compounds. It also describes navitoclax as targeting several Bcl-2 family proteins, rather than a single protein. (LLM, conf=0.87)

  cites [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
• Supported

  The Introduction describes navitoclax (ABT263) as inducing apoptosis in senescent HUVECs but not human preadipocytes. The Results report that A1331852 and A1155463 induced apoptosis and reduced survival in senescent HUVECs and IMR90 cells, but not senescent preadipocytes. No page numbers are supplied in our copy. (LLM, conf=0.92)

  cites [86] Zhu, Y. et al. New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging 9, 955–963 (2017). source

In the paper

“The intracellular and extracellular environment can modulate which SASP factors are produced and their abundance.”

What the sources say

• Supported

  In “SnCs have an altered response to SARS-CoV-2 spike protein” (page not provided), exposure to the extracellular S1 protein increased secretion of measured SASP factors, while the inflammatory profile differed among senescent cell types. Fig. 2 also reports that S1 had a more pronounced effect on senescent than nonsenescent cells, supporting a role for cellular state in SASP abundance. (LLM, conf=0.88)

  cites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). source

In the paper

“Second-generation senolytics are now being identified using high-throughput library screens and other approaches54.”

What the sources say

• Supported

  The Introduction says the authors used a screening platform and an autophagy-regulator library to identify HSP90 inhibitors as a novel class of senolytics. The Results describe screening 97 compounds, and the assay-qualification table identifies a parameter for high-throughput screening settings. The Discussion also mentions a bioinformatics approach used to identify other senolytics. Our copy does not provide page numbers for these passages. (LLM, conf=0.90)

  cites [54] Fuhrmann-Stroissnigg, H. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8, 422 (2017). source

In the paper

“Bioinformatic analyses identified 46 compounds that target SCAP pathways as being potentially senolytic14.”

What the sources say

• Partly supported

  The Results (Senolytic siRNAs; page unavailable) describe network analysis of pro-survival targets, and the Discussion proposes that drugs acting on several of those targets may be senolytic. Our copy does not say that bioinformatic analyses identified 46 compounds; the reported count is 39 transcripts selected for siRNA knockdown, not compounds. (LLM, conf=0.85)

  cites [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 the paper

“Other strategies for decreasing age-related senescent cell burden and pathologic conditions involve modulating immune clearance of senescent cells62.”

What the sources say

• Supported

  The Conclusions propose modulating immune responses to favor senescent-cell clearance as a therapeutic approach to age-related dysfunction and chronic disease. The Abstract likewise says that enhancing immune-mediated clearance could reduce senescent-cell burden. The source presents this as a potential strategy, not an established treatment. (LLM, conf=0.92)

  cites [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 the paper

“One approach stems from the increase in lysosomal mass and senescence-associated β-galactosidase activity in many senescent cells, whereby galacto-oligosaccharide-coated nanoparticles and β-galactosidase-activated prodrugs appear to eliminate at least some of these cells92,93.”

What the sources say

• Supported

  The Introduction and Discussion describe increased lysosomal mass and SAβGal activity in senescent cells as the basis for galacto-oligosaccharide-coated nanoparticles. The Results (‘Therapeutic activity of gal-encapsulated cytotoxic drugs on tumor xenografts’; page unavailable) report death of senescent cells treated with drug-loaded nanoparticles. This paper supports the nanoparticle part of the sentence; the separate prodrug approach is not attributed to it specifically. (LLM, conf=0.91)

  cites [92] Munoz-Espin, D. et al. A versatile drug delivery system targeting senescent cells. EMBO Mol. Med. 10, e9355 (2018). source
• Supported

  The Introduction (page not provided) links increased lysosomal mass and β-galactosidase activity in senescent cells to galacto-oligosaccharide nanoparticles that can deliver cell-killing cargo. The Discussion and Results (pages not provided) report that galactose-modified prodrugs selectively eliminate senescent cells through β-galactosidase-dependent activity. (LLM, conf=0.92)

  cites [93] Guerrero, A. et al. Galactose-modified duocarmycin prodrugs as senolytics. Aging Cell 19, e13133 (2020). source

In the paper

“in the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some of these extracellular cues are mediated through Toll-like receptor 3 and angiotensin converting enzyme-2, contributing to coronavirus disease 2019 (COVID-19) morbidity44,82.”

What the sources say

• Supported

  The Discussion reports that SARS-CoV-2 Spike-1 signals through ACE2 and amplifies the senescence-associated secretory phenotype (SASP), while viral exposure amplifies the SASP through TLR-3. The Abstract says these TLR-3-dependent effects may contribute to SARS-CoV-2 morbidity, matching the claim’s qualified wording. (LLM, conf=0.88)

  cites [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). source
• Partly supported

  The Introduction and Discussion (page numbers unavailable) describe ACE2 as a SARS-CoV-2 entry receptor and suggest that increased receptor expression may contribute to COVID-19 severity. Our copy does not describe extracellular cues acting through Toll-like receptor 3; searches for “TLR3” and “Toll-like receptor 3” found no supporting passage. (LLM, conf=0.88)

  cites [82] Kandhaya-Pillai, R. et al. TNF-α/IFN-γ synergy amplifies senescence-associated inflammation and SARS-CoV-2 receptor expression via hyper-activated JAK/STAT1. Aging Cell 21, e13646 (2022). sourceExperimental — accuracy not yet measured

In the paper

“SCAP pathways are similar to those that protect certain types of cancer cells, such as B cell lymphoma or chronic lymphocytic leukemia cells, which also release tissue-destructive proapoptotic factors but evade undergoing apoptosis themselves84,85.”

What the sources say

• Partly supported

  The sections on CLL-cell survival and its microenvironment describe pathways that protect CLL cells from apoptosis and suppress apoptosis in B-lymphoma cells. The microenvironment section also discusses chemokine secretion, but it does not identify the secreted factors as tissue-destructive or proapoptotic. That part of the attributed claim is unsupported. (LLM, conf=0.87)

  cites [84] Chen, L. S., Balakrishnan, K. & Gandhi, V. Inflammation and survival pathways: Chronic lymphocytic leukemia as a model system. Biochem. Pharmacol. 80, 1936–1945 (2010). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [85] Bessler, H. et al. Factor(s) released from irradiated B-CLL cells induce apoptosis in leukemic lymphocytes. Cancer Lett. 179, 103–108 (2002). source

In the paper

“SASP inhibitors (senomorphics) can directly or indirectly attenuate the SASP of senescent cells by inhibiting transcription factor nuclear factor (NF)-κB, the JAK-STAT signal transduction pathway, the serine/threonine protein kinase mTOR, mitochondrial complex-1-related or 4-related targets, or other pathways involved in the induction and maintenance of the SASP103–106.”

What the sources say

• ?Could not verify

  The paper’s Significance passage describes a capillary analog of muscle contraction driven by wetting affinity between silicone oil and a steel rod; its Keywords concern muscle contraction and force–velocity relations (page numbers unavailable). Searches for SASP inhibitors, senescent cells, NF-κB, JAK-STAT, mTOR, and mitochondrial targets found no passage addressing the attributed claim. (LLM, conf=0.79)

  cites [103] Xu, M. et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc. Natl Acad. Sci. USA 112, E6301–E6310 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not provided) reports that inhibiting IKK/NF-κB downregulated cytokines and other proinflammatory genes expressed by senescent cells, supporting the NF-κB part of the claim. It mentions mTOR as an activator of NF-κB, but does not show that inhibiting mTOR attenuates the SASP; the passages also do not support the JAK-STAT or mitochondrial-complex targets. (LLM, conf=0.88)

  cites [104] Tilstra, J. S. et al. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J. Clin. Invest. 122, 2601–2612 (2012). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The paper discusses compounds that inhibit mTORC1 (Abstract; page unavailable) and reports that rapamycin ameliorates premature senescence in progeria-derived cells (Abstract; page unavailable). Neither passage says that inhibiting mTOR—or the other listed pathways—attenuates the SASP. Searches for SASP and the named pathways found no passage addressing that relationship. (LLM, conf=0.76)

  cites [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
• Partly supported

  The Discussion reports that metformin reduces inflammatory cytokine production in senescent cells by interfering with NF-κB, and the Effects of metformin on the NF-κB pathway section reports inhibition of IKK activation. The paper does not establish SASP attenuation through JAK-STAT, mTOR, or mitochondrial complex-1- or complex-4-related targets, so it supports only part of the cited list. (LLM, conf=0.88)

  cites [106] Moiseeva, O. et al. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation. Aging Cell 12, 489–498 (2013). sourceExperimental — accuracy not yet measured

In the paper

“D + Q alleviated transcriptional changes and cellular dysfunction in an in vitro human neural cell Down syndrome model.”

What the sources say

• Supported

  The Introduction describes the model as human iPSC-derived neural progenitor cells and states that dasatinib plus quercetin alleviated transcriptional disruption and deficits in migration and proliferation in trisomy 21 cells. The Results section reports that DQ ameliorated approximately 54% of trisomy-21-induced differentially expressed genes and improved cellular function. (LLM, conf=0.94)

  cites [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

In the paper

“an RNA-mediated interference screen revealed that targeting alternative splicing in senescent cells may be a viable approach for inhibiting the SASP107.”

What the sources say

• Supported

  The Results section, “A Small Interfering RNA Screen Identifies SASP Regulators” (page unavailable), describes an siRNA screen that found genes whose knockdown reduced SASP markers IL-8 and IL-6. The Results section, “PTBP1 Regulates the SASP without Affecting Other Senescence Phenotypes” (page unavailable), identifies PTBP1 as an alternative-splicing regulator and reports that its knockdown suppressed inflammatory SASP components in senescent cells. The Discussion explicitly proposes regulating splicing as a strategy to repress the SASP. (LLM, conf=0.92)

  cites [107] Georgilis, A. et al. PTBP1-mediated alternative splicing regulates the inflammatory secretome and the pro-tumorigenic effects of senescent cells. Cancer Cell 34, 85–102 (2018). source

In the paper

“After resistance exercise, senescent cells develop in muscle of old mice in tandem with impaired exercise-induced muscle hypertrophy compared to young mice18.”

What the sources say

• Partly supported

  The Results (pages unavailable) show that senescent cells increased in old mouse muscle after mechanical overload and that hypertrophy was blunted compared with younger mice. The mouse intervention was surgically induced mechanical overload used to model resistance training, not resistance exercise itself; the paper reports resistance exercise separately in humans. (LLM, conf=0.84)

  cites [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

In the paper

“In mice infected with a murine coronavirus, the mortality rate was reduced following administration of D + Q or F16.”

What the sources say

• Supported

  In “Senolysis contributes to improved outcomes in old mice exposed to pathogens,” the paper reports that about 50% of aged female mice given D+Q or fisetin survived, whereas all vehicle-treated mice died. The Discussion identifies mouse hepatitis virus, a murine β-coronavirus, as a primary pathogen in the mixed-pathogen exposure and an essential contributor to mortality. The claim is supported in that setting, rather than as a result from coronavirus-only infection. (LLM, conf=0.89)

  cites [16] Camell, C. D. et al. Senolytics reduce coronavirus-related mortality in old mice. Science 373, eabe4832 (2021). source

In the paper

“A third copy of chromosome 21 in neural progenitor cells leads to transcriptional and nuclear organizational changes similar to those in senescent cells.”

What the sources say

• Supported

  The Introduction states that trisomy 21 alters genome organization and transcription in neural progenitor cells. It also says the architectural changes resemble those in senescent cells and that differentially expressed genes in trisomic progenitors are highly correlated with those in oxidative-stress-induced senescent cells. (LLM, conf=0.94)

  cites [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

In the paper

“D + Q alleviates this negative impact of aging on muscle growth.”

What the sources say

• Supported

  The Results section reports that, after 14 days of mechanical overload, old mice treated with D + Q had greater muscle mass and larger muscle fibers than vehicle-treated old mice. The Discussion likewise says D + Q augmented muscle growth in old mice under this condition. (LLM, conf=0.92)

  cites [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

In the paper

“An accelerated aging-like phenotype has been observed in astronauts who are exposed to radiation, high G-forces, zero gravity and cabin air quality126.”

What the sources say

• Partly supported

  The Discussion section on persistent telomere loss reports postflight telomere shortening and identifies telomere length as a biomarker of aging. The paper also discusses physiological changes associated with weightlessness and radiation exposure, but it does not establish an overall accelerated aging-like phenotype in astronauts or link one to high G-forces or cabin air quality. Its year-long flight findings are principally from one astronaut. (LLM, conf=0.84)

  cites [126] Garrett-Bakelman, F. E. et al. The NASA twins study: a multidimensional analysis of a year-long human spaceflight. Science 364, eaau8650 (2019). sourceExperimental — accuracy not yet measured

In the paper

“With senolytics, intermittent administration appears to be as effective as continuous treatment for attenuating senescent cell burden21.”

What the sources say

• Partly supported

  The treatment passage (indexed as Abstract; page unavailable) reports that once-monthly dasatinib plus quercetin reduced markers of senescent-cell burden in old mice. The Online Methods report similar effects with weekly and biweekly dosing, but the paper does not compare intermittent senolytic dosing with continuous senolytic treatment. The claimed equivalence to continuous treatment is therefore unsupported. (LLM, conf=0.86)

  cites [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

In the paper

“In vitro and in vivo, inhibitors of NF-κB (mediating the cell response to inflammation), can reduce pro-inflammatory SASP cytokines and chemokines104.”

What the sources say

• Partly supported

  The Discussion reports that 8K-NBD reduced expression of cytokine-related inflammatory genes and chemokines in treated mice. The Results report reduced senescence in cultured cells after genetic reduction of NF-κB, but do not report reduced SASP cytokines or chemokines in vitro. The source therefore supports the in vivo portion, not the full in vitro and in vivo claim. (LLM, conf=0.88)

  cites [104] Tilstra, J. S. et al. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J. Clin. Invest. 122, 2601–2612 (2012). sourceExperimental — accuracy not yet measured

In the paper

“Transplanted senescent cells or organs from old mice have been shown to spread the senescent phenotype to distant sites in recipient mice, predisposing to detrimental outcomes after transplantation24,31.”

What the sources say

• Partly supported

  The Results section on senescent-cell transplantation reports markers consistent with senescence spreading to distant muscle tissue and impaired physical function in recipient mice (page not provided). But the transplanted cells were experimentally induced to become senescent; this paper does not report transplanting organs from old mice or assessing organ-transplant outcomes. (LLM, conf=0.87)

  cites [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
• Partly supported

  The Introduction reports that transplanting senescent cells into young recipients causes functional impairment, and the Discussion says the senescence-associated secretory phenotype induces senescence locally and systemically. The Results also show poorer survival of untreated old-donor heart grafts. However, the paper does not show that transplanted old organs spread senescence to distant sites in recipients or establish that such spread causes the poor graft outcomes. (LLM, conf=0.86)

  cites [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

In the paper

“This intermittent ‘hit-and-run’ strategy of senolytic administration could serve to reduce side effects of agents such as D, which generally appear after weeks to months of continuous administration118,119.”

What the sources say

• Partly supported

  The Results (Safety; page unavailable) document adverse effects during daily dasatinib treatment, including pleural effusions and treatment interruptions. The paper does not establish that these effects generally begin after weeks to months, or test whether intermittent senolytic dosing reduces them; its regimen was daily dosing. (LLM, conf=0.82)

  cites [118] Naqvi, K. et al. Long-term follow-up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic-phase chronic myeloid leukemia. Cancer 126, 67–75 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  The paper’s long-term safety discussion (page unavailable) reports dasatinib-related adverse events during ongoing treatment, including pulmonary hypertension diagnosed on study days 36, 463, 838, and 944. It does not establish that side effects generally begin after weeks to months of continuous use, and it does not test intermittent senolytic dosing. The proposed benefit of that strategy is the citing authors’ inference. (LLM, conf=0.82)

  cites [119] Ottmann, O. et al. Long-term efficacy and safety of dasatinib in patients with chronic myeloid leukemia in accelerated phase who are resistant to or intolerant of imatinib. Blood Cancer J. 8, 88 (2018). sourceExperimental — accuracy not yet measured

In the paper

“over 20 clinical trials of senolytic therapies are completed, ongoing or planned34 (Table 1).”

What the sources say

• Partly supported

  In ‘Strategies for translating agents targeting fundamental ageing processes into treatments’ (page unavailable), the paper says several senolytic trials are underway or planned. Its Table 3 also lists studies that are completed, recruiting, or planned. Neither passage establishes the claimed total of over 20 clinical trials. (LLM, conf=0.86)

  cites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 1

In the paper

“NAD+ or NAD precursors can increase healthspan in experimental animals141.”

What the sources say

• Supported

  The “Aging and Longevity” section reports that NR treatment in old mice was associated with improved mitochondrial and stem-cell function, while long-term NMN treatment improved several measures of health in mice. It also reports benefits from NAD+ precursors in other experimental animals. These findings support the claim that NAD+ or its precursors can increase animal healthspan. (LLM, conf=0.93)

  cites [141] Rajman, L., Chwalek, K. & Sinclair, D. A. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 27, 529–547 (2018). source

In the paper

“in a mouse model of osteoarthritis, a combination of UBX0101 with N was necessary to restore aged joint structure131.”

What the sources say

• Supported

  The results passage (Volume 130, Number 10; page not supplied) identifies N as navitoclax (Navi) and reports that combined intra-articular UBX0101 and systemic Navi was the only regimen to significantly improve joint-structure scores in aged mice with osteoarthritis. It also says injecting both drugs into the joint did not improve tissue structure, so the systemic route matters. (LLM, conf=0.93)

  cites [131] Faust, H. J. et al. IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis. J. Clin. Invest. 130, 5493–5507 (2020). source

In the paper

“Results suggested that senolytics improved physical function in these frail patients.”

What the sources say

• Partly supported

  The Results (Functional and biological measures; page not provided) report improved walking distance, gait speed and chair-stand performance after senolytic treatment. The Introduction describes the participants as older adults with stable IPF, but the copy does not establish that they were frail. The Discussion also cautions that the open-label study lacked a control group, so the improvement cannot be attributed to treatment with certainty. (LLM, conf=0.82)

  cites [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

In the paper

“systemic, intermittent administration of senolytics for senescence-associated diseases is potentially more promising than local administration, with the exception of perhaps eye, skin or dental topical or other local applications34.”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [34] Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020). sourceExperimental — accuracy not yet measured

In the paper

“SASP factors, senescence markers and markers of other fundamental aging processes (for example, α-Klotho) can be assayed in body fluids such as urine, saliva, blood or cerebrospinal fluid7,19,48,59,61,64,132,133.”

What the sources say

• Partly supported

  Section 7, “Biomarkers of Senescent Cell Burden” (page unavailable), discusses possible blood and other body-fluid assays, SASP factors in plasma, and proposed assays of microvesicles shed into blood or urine. It does not mention α-Klotho, saliva, or cerebrospinal fluid, and says these assays still need development and validation rather than establishing that all the listed markers can be assayed in those fluids. (LLM, conf=0.86)

  cites [7] Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The Methods and Results describe assays of α-Klotho and SASP factors in urine, and the Discussion compares urinary α-Klotho assays with blood tests. The paper also mentions proposed testing of α-Klotho in cerebrospinal fluid, but our copy does not establish the full claim across all listed fluids and marker types, particularly saliva. (LLM, conf=0.85)

  cites [19] Zhu, Y. et al. Orally active, clinically translatable senolytics restore α-Klotho in mice and humans. EBioMedicine 77, 103912 (2022). sourceExperimental — accuracy not yet measured
• ?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 supported

  The Results section reports that SASP factors overlap with aging markers measured in human plasma, and the Discussion proposes SASP-based biomarkers in plasma or other biofluids. The paper does not establish the claim for urine, saliva, or cerebrospinal fluid, and it does not address α-Klotho. (LLM, conf=0.86)

  cites [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
• ?Could not verify

  The sections on SASP differences and endocrine effects (page unavailable) discuss SASP factors and senescence markers, but do not say they can be assayed in body fluids. Searches for urine, saliva, blood, cerebrospinal fluid, α-Klotho, and circulating biomarkers found no passage addressing the claimed assays. (LLM, conf=0.73)

  cites [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
• Partly supported

  The Research issues section (page unavailable) proposes blood biomarkers of senescent-cell burden based on detecting SASP products. It does not establish that such assays are available, or address α-Klotho or assays in urine, saliva, or cerebrospinal fluid. Searches for those fluids and α-Klotho found no supporting passage. (LLM, conf=0.85)

  cites [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
• Partly supported

  The Results and Discussion (page unavailable) discuss SASP factors and senescence markers, including genes used to identify senescent cells. They do not establish that these markers can be assayed in urine, saliva, blood, or cerebrospinal fluid, and the passages found do not address α-Klotho (searched: body fluids and α-Klotho). (LLM, conf=0.82)

  cites [132] Hernandez-Segura, A. et al. Unmasking transcriptional heterogeneity in senescent cells. Curr. Biol. 27, 2652–2660 (2017). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [133] Faget, D. V., Ren, Q. & Stewart, S. A. Unmasking senescence: context-dependent effects of SASP in cancer. Nat. Rev. Cancer 19, 439–453 (2019). source

In the paper

“post hoc analysis of a study involving 20 patients with IPF showed that urine levels of the ‘geroprotective’ factor α-Klotho were higher after oral D + Q than before treatment19.”

What the sources say

• Supported

  The Human IPF trial Methods describe a post hoc analysis of a study with 20 participants (2 at one site and 18 at the other) who received oral D+Q. The Results, under “Senolytics increase α-Klotho in humans,” report higher urinary α-Klotho after treatment than before it. Page numbers were not provided in the supplied passages. (LLM, conf=0.94)

  cites [19] Zhu, Y. et al. Orally active, clinically translatable senolytics restore α-Klotho in mice and humans. EBioMedicine 77, 103912 (2022). sourceExperimental — accuracy not yet measured

In the paper

“This could be especially important for older individuals or those with chronic diseases, who already have a high systemic senescent cell burden24,128.”

What the sources say

• Partly supported

  The Introduction (page not available) says senescent-cell burden increases in multiple tissues with aging and at sites of pathology in multiple chronic diseases. That supports the age and disease association, but not the stronger claim that people with chronic diseases already have a high systemic burden. The paper studies senolytic clearance, not the proposed importance of immune clearance in those people. (LLM, conf=0.84)

  cites [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
• Partly supported

  The ‘Physiological relevance of cellular senescence’ section reports that senescent cells increase with age, and ‘Cellular senescence in ageing’ reports accelerated local or systemic accumulation across a broad range of human diseases. The paper also suggests that removing persistent senescent cells might reduce dysfunction. It does not establish that older people or people with chronic diseases generally have a high *systemic* burden, or specifically recommend immune clearance for them; ‘Markers of cellular senescence’ says it is unclear whether local measurements reflect overall burden. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites [128] Khosla, S., Farr, J. N., Tchkonia, T. & Kirkland, J. L. The role of cellular senescence in ageing and endocrine disease. Nat. Rev. Endocrinol. 16, 263–275 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Dietary interventions, such as caloric restriction and intermittent fasting, might be protective against development of age-related dysfunction and diseases based on studies in animal models134,135.”

What the sources say

• ?Not checked — no full text of the sourcecites [134] Madeo, F., Carmona-Gutierrez, D., Hofer, S. J. & Kroemer, G. Caloric restriction mimetics against age-associated disease: targets, mechanisms and therapeutic potential. Cell Metab. 29, 592–610 (2019). source
• Supported

  The “DR and intrinsic aging” section reports that dietary restriction prevents age-related hearing loss and delays muscle decline and frailty in rodents. The “Impact of intermittent fasting on lifespan and healthspan” section reports reduced incidence of several chronic diseases in rodents, while noting that benefits are not universal. These passages support the citing sentence’s qualified claim about animal studies. (LLM, conf=0.91)

  cites [135] Green, C. L., Lamming, D. W. & Fontana, L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat. Rev. Mol. Cell Biol. 23, 56–73 (2022). source

In the paper

“The first senolytic clinical trial published was an open-label pilot study in which 14 patients with IPF were treated with intermittent D + Q on 3 d per week for 3 weeks63.”

What the sources say

• Supported

  The Abstract Methods describe an open-label pilot in 14 participants with IPF, using intermittent D+Q three days per week for three weeks. The Introduction calls it a first-in-human senolytic clinical trial, supporting the claim that it was the first published trial. (LLM, conf=0.93)

  cites [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). source

In the paper

“Analysis of proteomic and transcriptomic datasets revealed there is indeed upregulation of one or more senescent cell antiapoptotic pathways (SCAPs) in senescent cells.”

In the paper

“Unpublished work from our own laboratory suggests that there may be differences in the phenotypic effects (such as those relating to wound healing and healthspan) of targeting senescent cells in transgenic mice compared to the effects of senolytic agents in wild-type mice.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites unpublished data

In the paper

“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 the paper

“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 the paper

“if persistent, can have deleterious effects on tissue function due to the many proteins they secrete.”

In the paper

“Most cells undergoing senescence develop a SASP (Fig. 1).”

In the paper

“Although not every senescent cell develops a proapoptotic, inflammatory SASP, accumulation and persistence of such senescent cells can induce a chronic low-grade, pro-fibrotic inflammatory state (usually associated with aging and chronic diseases), known as ‘inflammaging’70.”

What the sources say

• ?Not checked — no full text of the sourcecites [70] Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69, S4–S9 (2014). source

In the paper

“Another approach is based on the high lysosomal activity of some senescent cells that renders them sensitive to lysosomal ATPase inhibitors94.”

What the sources say

• ?Not checked — no full text of the sourcecites [94] Dorr, J. R. et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501, 421–425 (2013). source

In the paper

“The first senolytic drugs were identified using a hypothesis-driven, mechanism-based drug discovery approach (Fig. 3).”

In the paper

“A possible advantage of small-molecule senolytics over vaccines or transplanted CAR T cells is that if a need for senescent cells occurs, for example, during wound healing, tissue remodeling or pregnancy, then treatment can be discontinued—whereas the continued elimination of senescent cells induced by vaccines or CAR T strategies may not readily be switched off.”

In the paper

“Suppressing the SASP without eliminating senescent cells is an alternative therapeutic approach for alleviating cellular senescence-related phenotypes or diseases.”

In the paper

“interventions that predominantly target the persisting, tissue-destructive SASP-expressing senescent cells might have superior therapeutic potential and fewer off-target effects.”

In the paper

“Elimination of all senescent cells or general inhibition of the SASP might be detrimental in some instances in which senescent cells are beneficial.”

In the paper

“Fibrosis can be a senescence-driven progressive process that contributes to reduced organ function”

In the paper

“senescent cells have been implicated in accentuating the severity of viral infections due to amplification of SASP factor secretion, predisposing to cytokine storm and multi-organ failure.”

In the paper

“Whereas SASP inhibitors potentially suppress both the growth-promoting as well as the proapoptotic, inflammatory, tissue-destructive sets of SASP factors”

In the paper

“First-generation senolytics, such as D + Q, have been tested in several preclinical models of aging and diseases, including type 2 diabetes, and bone, heart, kidney, liver, lung, muscle and neurological disorders (Table 2).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 2

In the paper

“α-Klotho overexpression in mice increases healthspan and lifespan by up to 30% (ref. 143).”

What the sources say

• ?Not checked — no full text of the sourcecites [143] Kurosu, H. et al. Suppression of aging in mice by the hormone Klotho. Science 309, 1829–1833 (2005). source

In the paper

“a phase 2, randomized, double-blind, placebo-controlled clinical trial (NCT04349956)—in which the senolytic agent was a p53-destabilizing protein MDM2 inhibitor, UBX0101 (also known as nutlin-3a)—did not achieve its primary endpoint of improving pain in patients with osteoarthritis of the knee in a 12-week follow-up.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites NCT04349956

In the paper

“The elimination of senescent cells has emerged as a plausible therapeutic strategy for preventing, delaying or alleviating multiple diseases and age-related dysfunction.”

In the paper

“the first gerodiagnostic score sensitive to senolytic administration in humans was a blood composite score published in 2019 (ref. 48).”

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

In the paper

“Identification and monitoring of senescent cell burden in situ, especially during clinical trials to assess safety and efficacy, can be challenging if solely based on analysis of tissue biopsies given the contextual and complex regulation of the senescent cell fate.”

In the paper

“The first in-human trial of senolytics (D + Q), the Hematopoietic Stem Cell Transplant Survivors Study, is still underway (NCT02652052; first patient dosed on 1 April 2016).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites NCT02652052