SenNet recommendations for detecting senescent cells in different tissues

In the paper

“Senescent podocytes in old mouse kidneys overexpress senescence markers and SASP factors, including Irf5, Cebpb, Jdp2, Ccl2, Ccl3, Ccl5, Ccl8, Mmp12, Mmp13 and Gsk3b.”

What the sources say

• Disputed

  The Results section on aging nephropathy reports that p21, a senescence marker, colocalized with an endothelial-cell marker but not with the podocyte marker nephrin in old mouse glomeruli. The SASP Results section reports MMP13 upregulation in whole kidneys, not in senescent podocytes. The paper identifies endothelial-cell senescence and podocyte loss, contrary to the claim's attribution of senescence-marker and SASP overexpression to podocytes; it does not report the claimed gene list in podocytes. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). sourceExperimental — accuracy not yet measured

In the paper

“During acinar-to-ductal metaplasia, dedifferentiated acinar cells acquire a senescent state characterized by cell cycle arrest, induction of p53, CDKN1A, CDKN2A and SA-β-gal activity190–193.”

What the sources say

• ?Not checked — no full text of the sourcecites [190] Grabliauskaite, K. et al. p21WAF1/Cip1 limits senescence and acinar-to-ductal metaplasia formation during pancreatitis. J. Pathol. 235, 502–514 (2015). source
• ?Not checked — no full text of the sourcecites [191] Horiguchi, M. et al. Senescence caused by inactivation of the homeodomain transcription factor Pdx1 in adult pancreatic acinar cells in mice. FEBS Lett. 593, 2226–2234 (2019). source
• Disputed

  The Abstract says that during oncogenic Kras-driven acinar-to-ductal metaplasia, quiescent acinar cells enter the cell cycle, rather than arrest in a senescent state. The Results report CDKN1A (p21) induction and growth arrest after E47 is introduced into pancreatic cancer cells to drive them back toward an acinar state; they do not establish the claimed senescence-marker pattern during metaplasia. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  cites [192] Kim, S. et al. The basic helix–loop–helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential. Pancreas 44, 718–727 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results sections on postnatal pancreatic senescence and p53 dependence report senescent acinar cells with cell-cycle arrest, SA-β-gal activity, increased p53, and increased Cdkn1a. They report induction of Cdkn2b, not Cdkn2a. The Results section on p53-dependent phenotypes describes morphology consistent with early acinar-to-ductal metaplasia in p53-deficient pancreata, where dedifferentiation markers became widespread; it does not establish that cells acquire this senescent state during metaplasia. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  cites [193] Tourlakis, M. E. et al. In vivo senescence in the Sbds-deficient murine pancreas: cell-type specific consequences of translation insufficiency. PLoS Genet. 11, e1005288 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Compared with brains of healthy individuals, the substantia nigra of individuals with Parkinson disease has reduced levels of SATB1 (a CDKN1A repressor) and increased levels of CDKN2A, MMP3, IL-6, IL-1α and CXCL8, suggesting an increased burden of senescence106,116.”

What the sources say

• Partly supported

  The Results section, “Senescent Astrocytes and SASP Factors Are Elevated in Parkinsonian Substantia Nigra Pars Compacta” (page not provided), reports increased p16INK4a, MMP-3, IL-6, IL-1α and IL-8 in Parkinsonian substantia nigra pars compacta tissue compared with controls, and interprets the findings as evidence of increased senescence. The paper does not report reduced SATB1 or identify it as a CDKN1A repressor; a search for SATB1 found no supporting passage. (LLM, conf=0.88)

  cites [106] Chinta, S. J. et al. Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson’s disease. Cell Rep. 22, 930–940 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section ('Validation of novel determinants of DA neurodegeneration'; page unavailable) reports significantly decreased SATB1 transcriptional activity in substantia nigra samples from people with incipient Parkinson disease versus controls. It explicitly says SATB1 expression levels did not change, contrary to the claimed reduction in levels. Our copy does not report increases in CDKN2A, MMP3, IL-6, IL-1α or CXCL8, or an increased senescence burden. (LLM, conf=0.87)

  cites [116] Brichta, L. et al. Identification of neurodegenerative factors using translatome-regulatory network analysis. Nat. Neurosci. 18, 1325–1333 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Therefore, detecting senescence-associated cell cycle arrest requires quantifying multiple factors and features17.”

What the sources say

• Supported

  The Cell-Cycle Arrest section states that no specific marker of senescent cell-cycle arrest has been identified and explicitly concludes that detection requires quantifying multiple factors and features. (LLM, conf=0.95)

  cites [17] Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019). source

In the paper

“A single-cell transcriptomics study identified a Cdkn1ahigh senescent-like cell population from aged mouse adipose tissue-derived mesenchymal stem cells, with additional upregulation of Il6, Il15, Vegfa, Cxcl2, Ccl2 and Cxcl1 (ref. 124).”

What the sources say

• Partly supported

  The single-cell transcriptome analysis (section labeled Abstract; no page supplied) identifies a Cdkn1a/p21-high senescent-like ADSC population that is more common in old donors. The paper also reports upregulation of several SASP-related genes in old-donor ADSCs overall, but the passages do not identify Il6, Il15, Vegfa, Cxcl2, Ccl2 and Cxcl1 as upregulated, or establish that this list is specific to the p21-high population. (LLM, conf=0.87)

  cites [124] Wang, B. et al. Transplanting cells from old but not young donors causes physical dysfunction in older recipients. Aging Cell 19, e13106 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Analysis of the SenMayo gene panel (Box 3) indicates that approximately 50% of monocytes in the bone marrow of older subjects could be senescent84.”

What the sources say

• Partly supported

  The Results section (‘SenMayo identifies senescent cells in scRNA-seq datasets’; page unavailable) reports that monocytes had the highest proportion of SASP-associated cells in a human bone-marrow dataset. It does not report that approximately 50% of monocytes were senescent or give that estimate specifically for older subjects. The Methods describe the single-cell donors as averaging 50.6 ± 14.9 years of age. (LLM, conf=0.86)

  cites [84] Saul, D. et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat. Commun. 13, 4827 (2022). sourceExperimental — accuracy not yet measured

In the paper

“CD3+ T cells isolated from the blood of aged mice and of mice deficient in ERCC1, which is a crucial DNA repair protein, exhibit increased levels of multiple senescent markers, including Ccl2, Tnf, Il1b, Inhba, Spp1, Cdkn2a and Cdkn1a (refs. 85,86).”

What the sources say

• Partly supported

  The Results on peripheral lymphocytes report increased Cdkn2a (p16Ink4a) and Cdkn1a (p21Cip1) in blood CD3+ T cells from aged and Ercc1-deficient mice. The Results on other measures of senescence also report elevated SASP-factor expression, including Ccl2/Mcp1, Tnf and Il1b, in peripheral T cells. Inhba/Activin A and Spp1/osteopontin were reported as elevated in serum, not in the isolated T cells, so the full gene list is not supported for those cells. (LLM, conf=0.88)

  cites [85] 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
• Partly supported

  The Immune cell senescence section reports increased senescence and SASP markers in peripheral CD3+ cells from aged ERCC1-deficient mice, analogous to aged wild-type mice. It identifies p16 (Cdkn2a), p21 (Cdkn1a), Ccl2, Tnf and Il1b among the markers studied, but does not establish that every listed gene increased in blood CD3+ cells in both groups. Searches for Inhba and Spp1 found no supporting passage. (LLM, conf=0.86)

  cites [86] 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

In the paper

“Human and mouse postmitotic cells and progenitor cell types of the central nervous system, including neurons, microglia, astrocytes, oligodendrocyte lineage cells and endothelial cells, exhibit overexpression of combinations of senescence-related cell cycle regulators (CDKN2A, TP53 and CDKN1A) and SASP factors (CCL2, IL1A, IL1B, IL6, MMP1, MMP3, SERPINE1, SPP1 and TNF) in the context of ageing and”

What the sources say

• Partly supported

  The Results (page unavailable) show that ageing mouse cortical and Purkinje neurons develop senescence-like markers, including increased IL-6, and link the phenotype to p21/CDKN1A. They do not establish the claimed overexpression across human CNS cells, progenitors, the other listed CNS cell types, or the broader panel of cell-cycle regulators and SASP factors. (LLM, conf=0.90)

  cites [99] Jurk, D. et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11, 996–1004 (2012). sourceExperimental — accuracy not yet measured
• Partly supported

  The Identification of cell types section (page unavailable) reports more cells with high senescence-gene scores among aged mouse endothelial cells and microglia, but not neurons. The gene list includes several of the named regulators and SASP factors. The study does not establish the claim for human cells or progenitors, or show overexpression across all the listed CNS cell types in ageing and disease. (LLM, conf=0.88)

  cites [100] Kiss, T. et al. Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain. Geroscience 42, 429–444 (2020). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [101] Jin, W. N. et al. Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition. Nat. Neurosci. 24, 61–73 (2021). source
• Partly supported

  The Results section (Figure 1; page unavailable) reports age-related increases in p16Ink4a- and p21-positive mouse brain cells, including microglia, oligodendrocyte-lineage cells, neurons and astrocytes, and links p16Ink4a expression to higher pro-inflammatory gene expression. The Introduction also notes senescence markers in endothelial cells. Our copy does not establish the claim for human CNS cells or document overexpression of the full named set of regulators and SASP factors across those cell types in ageing and disease. (LLM, conf=0.87)

  cites [102] Ogrodnik, M. et al. Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice. Aging Cell 20, e13296 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section reports increased P16INK4A in mouse hippocampal neural precursor cells with age, and increased Il6 in precursor cultures after experimentally induced senescence. The Introduction and Discussion also describe senescent glial cells in neurodegenerative disease. The paper does not establish the claimed overexpression pattern across human and mouse CNS cell types, including neurons and endothelial cells, or across the listed regulators and SASP factors. The indexed passages provide no page numbers. (LLM, conf=0.88)

  cites [103] Fatt, M. P. et al. Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche. Stem Cell Rep. 17, 259–275 (2022). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (page unavailable) reports that an aged-mouse myeloid/microglial population upregulates Cdkn2a, Cdkn1a and SASP factors including Ccl2 and Spp1. Although the paper identifies other brain cell types, these passages do not establish the stated expression pattern across those types or in humans; they also do not substantiate the full gene list or the broader disease context. (LLM, conf=0.88)

  cites [104] Zhang, X. et al. Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance. Nat. Commun. 13, 5671 (2022). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (page unavailable) reports increased p16INK4a, MMP3, and IL-6 in senescent astrocyte cultures, and increased senescence-associated markers in astrocytes of aged mouse hippocampus. The Introduction also describes senescence features in neural stem cells, neurons, and glia. The paper does not establish overexpression of the listed regulators and SASP factors across the full range of human and mouse CNS cell types named in the citing sentence. (LLM, conf=0.87)

  cites [105] Matias, I. et al. Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus. Aging Cell 21, e13521 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Myocardial infarction in mice was associated with increased expression of senescence-associated markers such as CDKN2A and CDKN1A, SA-β-gal activity, TAF and increased expression of SASP components in mouse cardiomyocytes67 and cardiac fibroblasts68.”

What the sources say

• Partly supported

  The Results (page unavailable) report p16 and p21 expression in hearts four weeks after MI and show that navitoclax-treated mice had lower expression than untreated mice. Figure 1 also documents p16-positive cardiomyocytes in aged mice, but before MI. The paper does not show that MI itself increased these markers relative to no MI, or establish the claimed post-MI changes in cardiac fibroblasts, SA-β-gal activity, or TAF. (LLM, conf=0.84)

  cites [67] Walaszczyk, A. et al. Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction. Aging Cell 18, e12945 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (‘Senescent fibroblasts accumulate in the infarcted heart in vivo’; page unavailable) reports increased SA-β-gal, p16 and p21 staining after infarction in mice and identifies the senescent cells as myofibroblasts. This supports the cardiac-fibroblast portion attached to this citation, but our copy does not report increased TAF; the cardiomyocyte portion is attached to a different citation. (LLM, conf=0.86)

  cites [68] Zhu, F. et al. Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial infarction. PLoS ONE 8, e74535 (2013). sourceExperimental — accuracy not yet measured

In the paper

“Post-mortem Alzheimer disease tissues also show elevated levels of SERPINE1, CDKN2A, CDKN2D, CDKN1A, IL-1β, IL-6 and CXCL8 in endothelial cells and microglia relative to control brain tissues112,115.”

What the sources say

• Partly supported

  The Results section, “Human microglia display markers of senescence in AD” (page not available), reports more P16+ and P21+ microglia in post-mortem AD cortex than in controls. It also reports increased PAI1, P19, P16, P21, IL-1β and IL-6 mRNA in temporal-cortex samples, but does not establish that all of these increases occur specifically in microglia. The cited passages do not report elevated CXCL8 or findings in endothelial cells. (LLM, conf=0.88)

  cites [112] Hu, Y. et al. Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology. Cell Rep. 35, 109228 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page unavailable in our copy) report elevated SERPINE1, CDKN1A, and CXCL8 in post-mortem prefrontal cortical microvessels from advanced-Braak-stage subjects compared with controls. They do not establish elevation in microglia: the study analyzed isolated microvessels, not those cells. CDKN2A was excluded because its expression was often undetectable, IL6 upregulation did not reach significance, and the reported upregulated-gene list does not include CDKN2D or IL-1β. (LLM, conf=0.90)

  cites [115] Bryant, A. G. et al. Cerebrovascular senescence is associated with tau pathology in Alzheimer’s disease. Front. Neurol. 11, 575953 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Multiple senescence-associated markers, including cell cycle inhibitors (Cdkn2a, Cdkn1a and Trp53), DNA damage foci and SASP factors, are upregulated in the aorta of ageing mice63–65.”

What the sources say

• ?Not checked — no full text of the sourcecites [63] Bhayadia, R., Schmidt, B. M., Melk, A. & Homme, M. Senescence-induced oxidative stress causes endothelial dysfunction. J. Gerontol. A Biol. Sci. Med. Sci. 71, 161–169 (2016). source
• Partly supported

  The Results section reports a more than sevenfold increase in Cdkn2a in aged mouse aortae, and the Results and Discussion report increased inflammatory mediators consistent with SASP. Our copy does not report upregulation of Cdkn1a or Trp53, or an increase in DNA damage foci in the aged aorta. Page numbers are not available in the indexed passages. (LLM, conf=0.88)

  cites [64] Gao, P. et al. Transcriptome analysis of mouse aortae reveals multiple novel pathways regulated by aging. Aging 12, 15603–15623 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section reports age-dependent increases in p53, p21 and p16 proteins, and the Figure 1 caption specifies that these were measured in mouse aortas. Our copy does not show that DNA damage foci were upregulated there; its discussion mentions inflammatory cytokines in old arteries but does not establish the full claimed set of SASP markers in the study's mouse aortas. Page numbers are unavailable in the indexed copy. (LLM, conf=0.86)

  cites [65] Yu, H. et al. Role of the cGAS–STING pathway in aging-related endothelial dysfunction. Aging Dis. 13, 1901–1918 (2022). sourceExperimental — accuracy not yet measured

In the paper

“In mice, aged cardiac mesenchymal stromal cells identified as PTPRC−PECAM1−ATXN1+PDGFRA+ (also knownas CD45−CD31−SCA1+PDGFRα+) experience a decline in clonogenic and proliferative capacity linked to increase mRNA expression of Cdkn1a, Cdkn2b and Cdkn2a and SASP factors61.”

What the sources say

• Supported

  The Results section on gene expression profiling reports that aged mouse cMSCs, sorted as Sca-1+/PDGFRα+/CD31−/CD45−, up-regulated Cdkn1a, Cdkn2b and Cdkn2a. It associates higher expression of these genes with fewer proliferating cells and decreased clonogenicity; Figure 1f reports SASP-gene mRNA in aged versus young cMSCs, and the Results describe SASP acquisition. No page number is available in our copy. (LLM, conf=0.92)

  cites [61] Martini, H. et al. Aging induces cardiac mesenchymal stromal cell senescence and promotes endothelial cell fate of the CD90+ subset. Aging Cell 18, e13015 (2019). source

In the paper

“Studies have identified oncogene-induced, irradiation-induced and ageing-induced accumulation of senescent cells in the bone marrow92–94.”

What the sources say

• Partly supported

  The paper reports senescence markers in bone-marrow hematopoietic stem cells after irradiation and says treatment clears senescent stem cells from the bone marrow of aged mice. It also induces oncogene (Ras)-driven senescence, but in cultured WI-38 cells, not bone marrow. Thus it does not support all three causes of bone-marrow senescent-cell accumulation attributed to the citation cluster. (LLM, conf=0.87)

  cites [92] 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
• Supported

  The Discussion reports that, with normal chronological aging, several cell types isolated from mouse bones and marrow become senescent. In this sentence with multiple citations, this source supports the ageing-induced component; it need not establish the oncogene- or irradiation-induced components. (LLM, conf=0.91)

  cites [93] Farr, J. N. et al. Identification of senescent cells in the bone microenvironment. J. Bone Miner. Res. 31, 1920–1929 (2016). source
• Partly supported

  The Key points (p. 2) and Discussion (p. 12) report that AML blasts induce senescence in bone marrow cells. The paper also says the bone marrow microenvironment becomes senescent with age (Abstract, p. 3). It does not establish irradiation-induced senescent-cell accumulation in bone marrow, so it supports only part of the cited sentence. (LLM, conf=0.85)

  cites [94] Abdul-Aziz, A. M. et al. Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment. Blood 133, 446–456 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Senescence-associated markers have also been identified in the context of vascular diseases such as atherosclerosis and abdominal aortic aneurysm and thoracic aortic aneurysm in both human and mouse models69–72.”

What the sources say

• Partly supported

  The Results (§2.5; page not provided) identify senescence-associated markers in human thoracic aortic aneurysm specimens, and the Introduction links senescence to atherosclerosis. The Introduction discusses telomere damage in abdominal aortic aneurysms and ROS in a murine aneurysm model, but does not identify senescence-associated markers in either abdominal aneurysms or mouse models. (LLM, conf=0.88)

  cites [69] Aschacher, T. et al. Impacts of telomeric length, chronic hypoxia, senescence, and senescence-associated secretory phenotype on the development of thoracic aortic aneurysm. Int. J. Mol. Sci. 23, 15498 (2022). sourceExperimental — accuracy not yet measured
• Supported

  The Results section, “SIRT1 Is Crucial for Suppression of Vascular Cell Senescence and p21 Expression in AAAs” (page unavailable), reports increased senescence-associated β-galactosidase staining in mouse aortas under AAA-inducing conditions and increased p21, a senescence marker, in human AAA samples. This paper supports the abdominal-aortic-aneurysm portion of the multiply cited sentence; it is not being relied on here for atherosclerosis or thoracic aortic aneurysm. (LLM, conf=0.91)

  cites [70] Chen, H. Z. et al. Age-associated sirtuin 1 reduction in vascular smooth muscle links vascular senescence and inflammation to abdominal aortic aneurysm. Circ. Res. 119, 1076–1088 (2016). source
• Partly supported

  The paper reports senescence-associated findings in atherosclerosis: its Abstract section describes shortened telomeres in human plaques, and the mouse experiments identify SA β-Gal activity and elevated senescence-marker transcripts in lesions. Our copy does not report such markers in abdominal or thoracic aortic aneurysms. No page number is available for these passages. (LLM, conf=0.88)

  cites [71] Childs, B. G. et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354, 472–477 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [72] Matthews, C. et al. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res. 99, 156–164 (2006). source

In the paper

“Studies have shown that immune cells, including monocytes and tissue-resident macrophages, are the predominant producers of SASP factors such as IL-1α, IL-1β, IL-6, TNF and HMGB1 (refs. 75–78).”

What the sources say

• Partly supported

  The “Metabolic disease/T2D” section (page not supplied) credits inflammatory M1 macrophages with increased TNFα, IL-6, and IL-1β in obesity. The “Age-related diseases and inflammation” section says macrophages are major responders to danger signals in aged tissues, but does not establish that monocytes and tissue-resident macrophages are the predominant producers of SASP factors generally, or identify them as producers of IL-1α and HMGB1. (LLM, conf=0.87)

  cites [75] Goldberg, E. L. & Dixit, V. D. Drivers of age-related inflammation and strategies for healthspan extension. Immunol. Rev. 265, 63–74 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  The section on decay of tissue-resident macrophage niches reports that inflammatory monocytes in IBD mucosa produce IL-6 and TNF-α. The section on disease-associated signals also lists activated immune cells among IL-6 producers, but it does not identify monocytes or tissue-resident macrophages as the predominant producers. Neither passage establishes that these cells predominantly produce SASP factors or supports the full list including IL-1α, IL-1β, and HMGB1. (LLM, conf=0.84)

  cites [76] Park, M. D., Silvin, A., Ginhoux, F. & Merad, M. Macrophages in health and disease. Cell 185, 4259–4279 (2022). sourceExperimental — accuracy not yet measured
• Partly supported

  The Main Text reports Il1b gene expression in bone-marrow-derived macrophages, and Extended Data Figure 7 examines senescence-associated genes in adipose-tissue macrophages. These findings support a limited link between macrophages, IL-1β and senescence-related changes, but do not establish that monocytes or tissue-resident macrophages are the predominant producers of the listed SASP factors. (LLM, conf=0.81)

  cites [77] Camell, C. D. et al. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 550, 119–123 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section reports that stimulated mouse peritoneal macrophages increased IL-1β gene expression, supporting a limited link between macrophages and one listed inflammatory factor. It does not establish that monocytes or tissue-resident macrophages are the predominant producers of SASP factors, or report production of the other listed factors. No page number is available in our copy. (LLM, conf=0.84)

  cites [78] Hall, B. M. et al. p16Ink4a and senescence-associated β-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

In the paper

“Senescent cells also persistently accumulate iron, even when the surge of extracellular iron level returned to normal after injury156.”

What the sources say

• Supported

  The Discussion states that iron continues to accumulate in fibrotic lesions after the initial burst of extracellular iron from tissue injury has subsided. It also explains that damaged and senescent cells accumulate intracellular iron even when extracellular iron levels are normal. No page numbers are provided in our copy. (LLM, conf=0.93)

  cites [156] Maus, M. et al. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat. Metab. 5, 2111–2130 (2023). source

In the paper

“Mouse hepatic stellate cells have also been shown to exhibit senescence-associated markers such as SA-β-gal activity and expression of Cdkn1a, Cdkn2a and SASP components in models of liver injury163,164.”

What the sources say

• Partly supported

  The Results section, “Senescent activated stellate cells accumulate in the cirrhotic liver,” reports that most SA-β-gal-positive cells in mouse fibrotic liver also expressed the stellate-cell marker αSMA. It reports p21 and p16 in injured mouse livers, but demonstrates their co-localization with αSMA in human liver sections. The Results section on immune modulators describes SASP-related gene expression in cultured human, not mouse, stellate cells; thus the full set of markers is not established for mouse stellate cells in liver-injury models. (LLM, conf=0.88)

  cites [163] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section, “Elimination of senescent cells impairs liver regeneration” (page unavailable), reports that mouse hepatic stellate cells isolated after partial hepatectomy showed increased SA-β-Gal activity, p16 (Cdkn2a) positivity, and SASP expression. It does not report Cdkn1a expression in those cells, so that marker is not supported by this source. (LLM, conf=0.87)

  cites [164] Cheng, N., Kim, K. H. & Lau, L. F. Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2. JCI Insight 7, e158207 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Furthermore, the expression in adipose tissue of certain markers, including IFI27129, INHBA121, BDNF130, NRIP1131 and CCAR2132, is positively correlated with senescence in ageing and other conditions.”

What the sources say

• ?Could not verify

  The citation is attached to CCAR2. The Results (section 2.3) and Discussion describe other cell-cycle regulators and senescence markers, but searches for CCAR2 and its alternative name DBC1 found no passage linking its adipose-tissue expression to senescence. No page numbers were available in our copy. (LLM, conf=0.76)

  cites [129] Colón-Mesa, I. et al. Regulation of p27 and cdk2 expression in different adipose tissue depots in aging and obesity. Int. J. Mol. Sci. 22, 11745 (2021). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section reports that adipose-tissue activin A correlated with senescent-cell burden in diet-induced obese mice, but it does not identify IFI27 in that finding. The citation to this paper is attached to IFI27; searches for IFI27 and its expanded name found no passage linking its adipose-tissue expression to senescence in ageing or other conditions. (LLM, conf=0.76)

  cites [121] Palmer, A. K. et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell 18, e12950 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (“Pro-BDNF expression increased in visceral white adipose tissue with advanced age”; page not provided) reports that pro-BDNF and senescence-associated markers increased in epididymal white adipose tissue of older mice. The finding supports the BDNF portion of the sentence, but not its extension to adipose tissue generally or to conditions other than ageing. The other named markers have separate citations and are not assessed here. (LLM, conf=0.86)

  cites [130] Song, H. D. et al. Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction. Aging Dis. 11, 575–587 (2020). sourceExperimental — accuracy not yet measured

In the paper

“In the context of primary biliary cirrhosis, which is an autoimmune disease characterized by chronic, progressive cholestasis and liver failure, senescence-associated markers have been found in cholangiocytes165.”

What the sources say

• Partly supported

  The Introduction and Results report senescent cholangiocytes in primary sclerosing cholangitis (PSC). The Discussion also describes senescent cholangiocytes in livers of patients with PSC, but the cited paper does not establish the claim for primary biliary cirrhosis. (LLM, conf=0.86)

  cites [165] 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). sourceExperimental — accuracy not yet measured

In the paper

“Il1b, Il6 and Mmp13 are also upregulated in old mouse kidneys140.”

What the sources say

• Supported

  The Results section, “Glomerular endothelial cell senescence is associated with SASP” (page unavailable), explicitly reports that IL-1β, IL-6 and MMP13 were upregulated in kidneys of old mice compared with young mice. (LLM, conf=0.95)

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). source

In the paper

“SERPINE1 and CDKN2A, produced by senescent glomerular endothelial cells, increase with age in kidneys from healthy kidney donors140,145.”

What the sources say

• Supported

  The Results section, “Glomerular endothelial cell senescence is associated with poor renal outcomes in humans” (page unavailable), reports higher glomerular PAI-1 (SERPINE1) and p16 (CDKN2A) staining in kidneys from older than younger donors with normal renal function. PAI-1 was found near glomerular endothelial cells, while p16 colocalized with an endothelial marker; the authors interpret the matching staining as evidence that senescent cells secrete PAI-1. (LLM, conf=0.92)

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). source
• ?Not checked — no full text of the sourcecites [145] Sis, B. et al. Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease. Kidney Int. 71, 218–226 (2007). source

In the paper

“SERPINE1 drives glomerulosclerosis in early kidney injury in diabetes140,148.”

What the sources say

• Partly supported

  The Results identify PAI-1, encoded by SERPINE1, as a mediator of age-related glomerulosclerosis in mice. They do not establish that it drives glomerulosclerosis in early diabetic kidney injury; the human aging-nephropathy cohort explicitly excluded patients with diabetes (Results, “Urinary PAI-1 is associated with aging nephropathy in humans”; page unavailable). (LLM, conf=0.90)

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (‘4 Days’; page unavailable) report increased PAI-1, the protein encoded by SERPINE1, in diabetic rat kidneys at day 10. The Discussion (‘4 Days’; page unavailable) suggests that a senescent phenotype may contribute to diabetic fibrosis, but does not show that SERPINE1 drives glomerulosclerosis. The passage mentioning reduced glomerulosclerosis concerns p27 knockout, not SERPINE1. (LLM, conf=0.86)

  cites [148] Satriano, J. et al. Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes. Am. J. Physiol. Cell Physiol. 299, C374–C380 (2010). sourceExperimental — accuracy not yet measured

In the paper

“Senescent cells are also observed in kidneys of mouse models of acute kidney injury, diabetic nephropathy, glomerulonephropathy, chronic kidney disease and chronic ischaemic renal injury140,144–150.”

What the sources say

• Partly supported

  The Results section reports senescent glomerular cells in aged mice, and the Discussion describes senescence in diabetic nephropathy and other glomerular diseases. Those passages support part of the disease-related claim, but they do not establish the full list as findings in mouse models: the paper does not report senescent kidney cells in models of acute kidney injury or chronic ischaemic renal injury. (LLM, conf=0.84)

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Fig. 4; page unavailable) show senescence markers in the kidneys of aging mice, and the Discussion reports greater podocyte senescence and kidney injury after podocyte-specific C/EBPα deletion. The paper does not show senescent cells in mouse models of acute kidney injury, diabetic nephropathy, chronic kidney disease, or chronic ischaemic renal injury; its model is aging-related kidney injury. (LLM, conf=0.84)

  cites [144] Zhang, L. et al. C/EBPɑ deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice. Cell Death Dis. 10, 684 (2019). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [145] Sis, B. et al. Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease. Kidney Int. 71, 218–226 (2007). source
• Supported

  The Results (§3.2, Renal senescence) report senescence-associated staining in the kidneys of diabetic mice, particularly in cortical tubules, but not in non-diabetic controls. This supports the diabetic-nephropathy mouse-model portion of the multi-cited sentence; the other listed conditions are not attributed specifically to this paper. (LLM, conf=0.92)

  cites [146] Kitada, K. et al. Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J. Diabetes Complications 28, 604–611 (2014). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [147] Verzola, D. et al. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am. J. Physiol. Ren. Physiol. 295, F1563–F1573 (2008). source
• Partly supported

  The Abstract reports increased senescence-associated β-galactosidase activity in the cortical tubules of diabetic rat kidneys, supporting the diabetes-related observation. It does not establish that observation in a mouse model, and this paper does not provide evidence for the other kidney-injury models listed in the multi-citation sentence. (LLM, conf=0.88)

  cites [148] Satriano, J. et al. Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes. Am. J. Physiol. Cell Physiol. 299, C374–C380 (2010). sourceExperimental — accuracy not yet measured
• Supported

  The citation supports the chronic ischaemic renal injury item in the multi-citation list. The Discussion reports elevated senescence markers in stenotic kidneys from the study’s mouse model of chronic renal ischaemia. (LLM, conf=0.91)

  cites [149] Kim, S. R. et al. Increased cellular senescence in the murine and human stenotic kidney: effect of mesenchymal stem cells. J. Cell. Physiol. 236, 1332–1344 (2021). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [150] Westhoff, J. H. et al. Telomere shortening reduces regenerative capacity after acute kidney injury. J. Am. Soc. Nephrol. 21, 327–336 (2010). source

In the paper

“Senescent glomerular endothelial cells overexpress CDKN1A, the DNA damage markers TP53BP1 and γH2AX, and SERPINE1140,142,143.”

What the sources say

• Supported

  In Results (‘Aging nephropathy is associated with glomerular endothelial cell senescence’; page not supplied), p21, 53BP1 and phosphorylated H2AX staining increased in glomerular endothelial cells of old mice. Results (‘Endothelial PAI-1 induces podocyte detachment and apoptosis’; page not supplied) also report higher PAI-1 expression in senescent human glomerular endothelial cells. These correspond to CDKN1A, TP53BP1, γH2AX and SERPINE1, respectively. (LLM, conf=0.91)

  cites [140] Cohen, C. et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol. Med. 13, e14146 (2021). source
• Partly supported

  The Results section, “Endothelial cells and macrophages are SASP-carrying cells in vivo” (page unavailable), reports a senescence-associated signature in kidney endothelial cells, but does not identify them specifically as glomerular endothelial cells. The Results section on SOD-1 overexpression reports increased p21 (CDKN1A) and PAI-1 (SERPINE1) in cultured endothelial cells, not glomerular endothelial cells; our copy does not report TP53BP1 or γH2AX overexpression. (LLM, conf=0.86)

  cites [142] Prattichizzo, F. et al. Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages. Redox Biol. 15, 170–181 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section on senescence signaling in glomerular podocytes reports increased p21 (CDKN1A), uses γH2AX staining to assess senescence, and identifies PAI-1 (SERPINE1) as a senescence-associated factor. Those findings concern podocytes, not glomerular endothelial cells; γH2AX is not reported there as overexpressed, and the searched passages do not report TP53BP1 overexpression. (LLM, conf=0.84)

  cites [143] Fang, Y. et al. Age-related GSK3β overexpression drives podocyte senescence and glomerular aging. J. Clin. Invest. 132, e141848 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Of note, a recent study demonstrated that iron accumulation, as a result of vascular and haemolytic injuries or other causes, promotes fibrosis and senescence in the kidney and other organs156.”

What the sources say

• Supported

  The Discussion states that iron overload from vascular or haemolytic insults can initiate fibrosis and senescence in some circumstances. The Results report evidence from kidney injury, while the Discussion says the finding is not limited to one organ or insult. The supplied passages do not provide page numbers. (LLM, conf=0.92)

  cites [156] Maus, M. et al. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat. Metab. 5, 2111–2130 (2023). source

In the paper

“However, a different study did not identify any senescent markers in α-cells from NOD mice or in the pancreas from donors with type 1 diabetes187.”

What the sources say

• Partly supported

  The Results sections report no Cdkn1a or Mmp2 staining in NOD mouse α-cells and no CDKN1A staining in α-cells from human type 1 diabetes donors. But the human donor pancreas sections did contain CDKN1A-positive insulin-producing cells, so the absence of markers applies to α-cells, not to the pancreas as a whole. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  cites [187] Brawerman, G., Ntranos, V. & Thompson, P. J. ɑ cell dysfunction in type 1 diabetes is independent of a senescence program. Front. Endocrinol. 13, 932516 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Similarly, senescent lung fibroblasts have a pivotal role in the pathogenesis of fibrotic lung diseases156,172.”

What the sources say

• Partly supported

  The Main section says senescent cells can directly contribute to fibrosis, while also noting that senescence can limit fibrogenesis. The Discussion identifies senescence-associated markers in lung fibroblasts and links such cells to idiopathic pulmonary fibrosis, but the paper does not establish that senescent lung fibroblasts have a pivotal role across fibrotic lung diseases. Page numbers are unavailable in our copy. (LLM, conf=0.83)

  cites [156] Maus, M. et al. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat. Metab. 5, 2111–2130 (2023). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction states that the accumulation of senescent fibroblasts drives pulmonary fibrosis. This supports the claimed role of senescent lung fibroblasts in fibrotic lung disease; page numbers are not available in the supplied copy. (LLM, conf=0.91)

  cites [172] Zhong, W. et al. Extracellular HSP90α promotes cellular senescence by modulating TGF-β signaling in pulmonary fibrosis. FASEB J. 36, e22475 (2022). source

In the paper

“Additionally, sex-biased islet β-cell dysfunction can be caused by a type of maturity-onset diabetes of the young secondary to the MAFA S64F variant, where a single amino acid substitution in the transcription factor MAFA leads to diabetes and accumulation of senescent cells in males185.”

What the sources say

• Supported

  The Introduction identifies MAFA S64F as a single-amino-acid substitution associated with MODY and reports that diabetes is more prevalent in male carriers. The Discussion reports accumulation of senescent cells in male MafA S64F mouse islets, while the Introduction describes senescence in male human β cells expressing the variant. No page numbers are provided in our copy. (LLM, conf=0.92)

  cites [185] Walker, E. M. et al. Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males. Cell Rep. 37, 109813 (2021). source

In the paper

“Studies have associated increased cell cycle arrest markers (CDK1A and p53), SASP factors (CXCL5, CXCL8 and VEGFA), SA-β-gal activity and γH2AX with increased cellular senescence in chronic obstructive pulmonary disease175,176.”

What the sources say

• Partly supported

  The Results and Discussion report that bronchial epithelial cells exposed to serum from COPD patients had increased p21, SA-β-Gal and γ-H2A.X, along with increased secretion of the SASP factors VEGF, CXCL8 and CXCL5. The paper does not report an increase in p53; it measured p21 as the cell-cycle inhibitor. Its findings are from serum-treated cells in culture, rather than direct measurements of senescence in patients with COPD. (LLM, conf=0.90)

  cites [175] Kuźnar-Kamińska, B. et al. Serum from patients with chronic obstructive pulmonary disease induces senescence-related phenotype in bronchial epithelial cells. Sci. Rep. 8, 12940 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction links P53 and P21 to cell-cycle arrest and senescence in COPD-related models. Results §3.3 reports increased P53, P21 and SA-β-gal-positive cells in H₂O₂-treated bronchial epithelial cells. Our copy does not identify CXCL5, CXCL8 or VEGFA as SASP factors here, or report γH2AX as a senescence marker, so it supports only part of the cited list. (LLM, conf=0.88)

  cites [176] Xiaofei, Y., Tingting, L., Xuan, W. & Zhiyi, H. Erythromycin attenuates oxidative stress-induced cellular senescence via the PI3K–mTOR signaling pathway in chronic obstructive pulmonary disease. Front. Pharmacol. 13, 1043474 (2022). sourceExperimental — accuracy not yet measured

In the paper

“These KRAS mutations are also found in the early stages of pancreatic ductal adenocarcinoma, preceding the appearance of senescence markers such as p53, CDKN2A and SMAD4196.”

What the sources say

• Partly supported

  The Discussion states that mutant KRAS is detected in the earliest human PanINs, and the introductory section explicitly places INK4A/ARF mutations at a later PanIN stage. The Molecular analyses section says p53 and SMAD4 alterations often occur in advanced human pancreatic adenocarcinomas, but does not explicitly establish their order relative to KRAS or identify all three genes as senescence markers. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  cites [196] Aguirre, A. J. et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes. Dev. 17, 3112–3126 (2003). sourceExperimental — accuracy not yet measured

In the paper

“In aged mice, markers of senescence have been found in osteoblast progenitors, osteoblasts and osteocytes using magnetic-activated cell sorting followed by qPCR.”

What the sources say

• Supported

  The Results report higher p16Ink4a expression by rt-qPCR in osteoblast progenitors, osteoblasts, and osteocytes from old versus young mice. The Results also describe the isolation workflow as a MACS-based approach, although the Methods specify that the osteocyte-enriched fraction was obtained by collagenase digestion rather than directly sorted by MACS. Page numbers were not available in our copy. (LLM, conf=0.90)

  cites [93] Farr, J. N. et al. Identification of senescent cells in the bone microenvironment. J. Bone Miner. Res. 31, 1920–1929 (2016). source

In the paper

“Disease states resulting from focal radiation therapy also induce skeletal senescence, characterized — similar to fracture — by early Cdkn1a and late Cdkn2a expression202.”

What the sources say

• Supported

  The Discussion reports early and late senescence responses in focally irradiated bone, marked by upregulation of p21 (Cdkn1a) and p16Ink4a (Cdkn2a), respectively. The Results section supports the timing: p21 peaked on day 1, while p16Ink4a reached its highest expression on day 42. No page numbers are available in our copy. (LLM, conf=0.93)

  cites [202] Chandra, A. et al. Targeted reduction of senescent cell burden alleviates focal radiotherapy-related bone loss. J. Bone Miner. Res. 35, 1119–1131 (2020). source

In the paper

“Moreover, SERPINE1 was shown to induce mouse alveolar type 2 (ATII) cellular senescence through activation of the p53–CDKN1A–RB1 pathway in fibrotic lung disease170.”

What the sources say

• Supported

  The Abstract reports that ATII-cell-specific PAI-1 knockout mice support a role for PAI-1 in activating the p53–p21–Rb pathway and promoting ATII-cell senescence in bleomycin-induced lung fibrosis. The Discussion also states that PAI-1 promotes ATII-cell senescence through this pathway in vitro and in vivo. CDKN1A and RB1 are the gene names for p21 and Rb; the supplied passages do not give page numbers. (LLM, conf=0.92)

  cites [170] Jiang, C. et al. Serpine 1 induces alveolar type II cell senescence through activating p53–p21–Rb pathway in fibrotic lung disease. Aging Cell 16, 1114–1124 (2017). source

In the paper

“In a mouse model of type 2 diabetes mellitus (high-fat diet with streptozotocin), osteocyte-enriched samples demonstrated increased expression of Cdkn2a and Cdkn1a, along with SASP markers predominantly related to NF-κB signalling and matrix metalloproteinases204.”

What the sources say

• Supported

  The section on osteocyte senescence in the HFD/STZ model reports significantly increased Cdkn2a and Cdkn1a expression in osteocyte-enriched bone samples. The same section reports a SASP dominated by elevated matrix metalloproteinases, alongside elevated Nfkb1 expression in those samples. (LLM, conf=0.94)

  cites [204] Eckhardt, B. A. et al. Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes. JCI Insight 5, e135236 (2020). source

In the paper

“In injury-induced senescence mouse models, SASP factors including cytokines (IL-1α, IL-1β, IL-10, TNF, TNFRSF1B and TNFSF12), chemokines (CXCL2 and CXCL12) and proteases (MMP8 and MMP12) are robustly upregulated168.”

What the sources say

• Partly supported

  The Results section, “Neonatal hyperoxia induces senescence-associated secretory phenotype (SASP)” (page unavailable), reports significant increases in IL-1α, IL-1β, CXCL2, CXCL12, and TNFRSF1B in lungs of hyperoxia-exposed neonatal mice. It lists IL-10, TNF, TNFSF12, MMP8, and MMP12 among the factors tested, but does not report that those factors were significantly increased; the citing sentence overstates the finding for the full list. (LLM, conf=0.90)

  cites [168] Yao, H. et al. Timing and cell specificity of senescence drives postnatal lung development and injury. Nat. Commun. 14, 273 (2023). sourceExperimental — accuracy not yet measured

In the paper

“Another reported hallmark of senescent fibroblasts, in idiopathic pulmonary fibrosis, is the enhanced expression of anti-apoptotic BCL2 family proteins such as BCL2L2, BCL2 and BCL2L1 along with reduced levels of the pro-apoptotic proteins BAK1 and BAX180,181.”

What the sources say

• ?Not checked — no full text of the sourcecites [180] Sanders, Y. Y. et al. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur. Respir. J. 43, 1448–1458 (2014). source
• Partly supported

  The Results section ('Senescent cells upregulate proteins of the Bcl-2 family'; page unavailable) reports increased BCL-W, BCL-XL and BCL-2 in experimentally senescent fibroblasts. It does not establish that finding in idiopathic pulmonary fibrosis or report reduced BAK1 and BAX; searches for those terms and pulmonary fibrosis found no such result. (LLM, conf=0.88)

  cites [181] Yosef, R. et al. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat. Commun. 7, 11190 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Mouse models of insulin resistance induced by a high-fat diet and the insulin receptor antagonist S961 exhibit elevation of SA-β-gal activity, and expression of Cdkn1a, Cdkn2a and the SASP factors Il1a, Il6, Tnf, Ccl3, Ccl4, Ccl5, Cxcl1 and Cxcl10 (ref. 182).”

What the sources say

• Partly supported

  The Results section, “Insulin resistance accelerated the appearance of senescent β-cells” (page unavailable), reports increased β-gal-positive cells and aging and SASP gene-expression indices after both S961 treatment and high-fat diet. The Methods section defines those indices to include p21, p16, Il1a, Il6 and TNFα, but not Ccl3, Ccl4, Ccl5, Cxcl1 or Cxcl10; it also does not establish that every listed gene rose individually in both models. (LLM, conf=0.88)

  cites [182] Aguayo-Mazzucato, C. et al. Acceleration of β cell aging determines diabetes and senolysis improves disease outcomes. Cell Metab. 30, 129–142.e4 (2019). sourceExperimental — accuracy not yet measured

In the paper

“In late puberty, mesenchymal stem/progenitor cells undergo normal programmed senescence, indicated by the loss of nestin expression199.”

What the sources say

• Supported

  The Introduction states that senescence of cells in the primary spongiosa during late puberty is characterized by loss of nestin expression and describes MSPC senescence as a normal programmed cell fate change. The Results section, “Senescent MSPCs is featured by loss of nestin expression,” reports senescence markers in nestin-negative MSPCs and identifies loss of nestin expression as a feature of senescence-like cell-cycle arrest in late puberty. (LLM, conf=0.94)

  cites [199] Li, C. et al. Programmed cell senescence in skeleton during late puberty. Nat. Commun. 8, 1312 (2017). source

In the paper

“In human bone biopsies, older women (mean age 78 years) show upregulated mRNA expression of CDKN2A, CDKN1A and senescence-associated chemokines (for example, CCL2, CCL3, CCL8 and CSF1)93 compared with younger women.”

What the sources say

• Partly supported

  Materials and Methods reports bone biopsies from older women with a mean age of 78 years, and Results reports higher p16Ink4a (CDKN2A) and p21 (CDKN1A) expression than in younger women. Results also reports 12 elevated SASP factors, but the passages do not identify CCL2, CCL3, CCL8 and CSF1 as elevated in the human biopsies; the paper calls those factor findings preliminary because the group-wide analysis was not statistically significant. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites [93] Farr, J. N. et al. Identification of senescent cells in the bone microenvironment. J. Bone Miner. Res. 31, 1920–1929 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Additionally, CDKN1A, p53 and γH2AX are also upregulated in mouse and human lungs upon senescence168,169.”

What the sources say

• Partly supported

  The Results sections on p21/p53 and DNA damage (pages unavailable) report increased Cdkn1a (p21), phosphorylated p53, and γH2AX in neonatal mouse lungs after hyperoxia, but total p53 did not increase and γH2AX rose only at the early time point. The Discussion reports increased p21/γH2AX colocalization in hyperoxia-exposed human infant airways, but does not establish that all three markers are upregulated in human lungs upon senescence. (LLM, conf=0.87)

  cites [168] Yao, H. et al. Timing and cell specificity of senescence drives postnatal lung development and injury. Nat. Commun. 14, 273 (2023). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results sections on mouse alveolar regeneration and human fibrotic lungs report increased CDKN1A and γH2AX in specific transitional epithelial cells associated with senescence and DNA damage. The human-lung Results also report enriched p53 signalling, but not an increase in p53 itself. The evidence concerns injured mouse lungs and human lungs with pulmonary fibrosis, rather than mouse and human lungs generally upon senescence; page numbers are unavailable in our copy. (LLM, conf=0.86)

  cites [169] Kobayashi, Y. et al. Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis. Nat. Cell Biol. 22, 934–946 (2020). sourceExperimental — accuracy not yet measured

In the paper

“By contrast, recent studies provide evidence for the accumulation of iron in the senescent fibrotic tissues from both mouse and human, thereby emphasizing the role of cellular metabolism in senescence156.”

What the sources say

• Supported

  The Results section, “Fibrogenic injuries provoke progressive iron accumulation,” reports iron in fibrotic mouse lungs, hearts and kidneys and in lung and kidney tissue from human patients. The Discussion links iron accumulation in human idiopathic pulmonary fibrosis to cells expressing senescence-related markers. (LLM, conf=0.93)

  cites [156] Maus, M. et al. Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat. Metab. 5, 2111–2130 (2023). source

In the paper

“Extracellular HSP90AA1 activates TGFβ1 signalling and promotes Trp53 and Cdkn1a expression to induce mouse and human pulmonary fibroblast senescence172.”

What the sources say

• Partly supported

  The Results and Discussion report that extracellular HSP90α activates TGF-β signaling, promotes p53 and p21 transcription, and induces senescence in human IMR90 lung fibroblasts. The Methods identify those cells as human; the mouse experiments examined lung tissue, not the same mechanism in isolated mouse pulmonary fibroblasts. The cited passages also identify TGF-β signaling without establishing the β1 isoform specifically. (LLM, conf=0.87)

  cites [172] Zhong, W. et al. Extracellular HSP90α promotes cellular senescence by modulating TGF-β signaling in pulmonary fibrosis. FASEB J. 36, e22475 (2022). sourceExperimental — accuracy not yet measured

In the paper

“CDKN2A-mediated senescence has also been shown to modulate the cigarette smoke-mediated senescence response in the mouse model for chronic obstructive pulmonary disease177,178.”

What the sources say

• Supported

  The Methods (Animals; page unavailable) identify the p16-deficient mice as carrying a Cdkn2a modification. The Results (‘p16 deletion blocks the pathophysiological changes associated with cigarette smoke’; page unavailable) report that cigarette smoke increased a senescence marker in wild-type mouse lungs but not in p16-deficient lungs, supporting the claimed modulation of the smoke-induced senescence response. (LLM, conf=0.93)

  cites [177] Cottage, C. T. et al. Targeting p16-induced senescence prevents cigarette smoke-induced emphysema by promoting IGF1/Akt1 signaling in mice. Commun. Biol. 2, 307 (2019). source
• Supported

  The Discussion (page unavailable) reports that cigarette smoke increased senescent cells in p16-3MR mouse lungs and that removing p16-positive cells reduced that senescence. It explicitly limits the findings to p16-mediated regulation of cellular senescence, supporting the claim about CDKN2A/p16 in this cigarette-smoke mouse model. (LLM, conf=0.92)

  cites [178] Kaur, G., Muthumalage, T. & Rahman, I. Clearance of senescent cells reverts the cigarette smoke-induced lung senescence and airspace enlargement in p16-3MR mice. Aging Cell 22, e13850 (2023). source

In the paper

“Markers of senescence have also been found in α-cells, such as Cdkn1a, Cdkn2a and loss of nuclear Hmgb1 in NOD mice, albeit at a lower rate than in β-cells in the same mice186.”

What the sources say

• Supported

  The Results section (“Protein Levels of Hallmark Genes for Beta Cell Senescence Are Regulated by PAHSA Treatment in NOD Mice,” Fig. 1K–L) reports p21Cip1 and p16Ink4 staining and loss of nuclear HMGB1 in α-cells of NOD mice. It states that these senescence markers were less frequent or less intense in α-cells than in β-cells from the same pancreatic sections. The paper reports protein-level markers; Cdkn1a and Cdkn2a name the corresponding genes. (LLM, conf=0.92)

  cites [186] Rubin de Celis, M. F. et al. PAHSAs reduce cellular senescence and protect pancreatic β cells from metabolic stress through regulation of Mdm2/p53. Proc. Natl Acad. Sci. USA 119, e2206923119 (2022). source

In the paper

“The same profile was found in individuals with chronic pancreatitis194.”

What the sources say

• ?Could not verify

  The Methods section measures acinar-to-ductal metaplasia in mice, while the Discussion links a pancreatic stellate-cell marker to chronic pancreatitis in clinical datasets. Neither passage identifies a senescence profile or shows that the same profile occurs in metaplasia and people with chronic pancreatitis; searches for “senescence” and that comparison found no such passage (page numbers unavailable). (LLM, conf=0.76)

  cites [194] Hu, C. et al. The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis. Comput. Struct. Biotechnol. J. 19, 6375–6385 (2021). sourceExperimental — accuracy not yet measured

In the paper

“In both ageing and the disease states listed above, skeletal cellular senescence can also be observed through histological staining of SA-β-gal activity203, SADS93,200,204,205 and TAF200,203,204, typically in bone-embedded osteocytes206.”

What the sources say

• Supported

  Citation 206 is attached to the statement that skeletal senescence is typically observed in bone-embedded osteocytes, rather than to the list of staining methods. The Results section evaluates TAF-positive osteocytes and describes osteocytes as the largest fraction of bone cells and a major senescent-cell component in age-related bone loss. (LLM, conf=0.88)

  cites [203] Chandra, A. et al. Targeted clearance of p21- but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity. Aging Cell 21, e13602 (2022). source
• Supported

  Citation 206 is attached specifically to “typically in bone-embedded osteocytes,” not to the preceding list of staining methods. The Results report that in vivo SADS measurements found more senescent osteocytes in old than young bone cortices, supporting the osteocyte identification in ageing bone. No page number is available in our copy. (LLM, conf=0.91)

  cites [93] Farr, J. N. et al. Identification of senescent cells in the bone microenvironment. J. Bone Miner. Res. 31, 1920–1929 (2016). source
• Partly supported

  The Introduction (page unavailable) includes osteocytes among several skeletal cell populations linked to ageing, and the SADS methods describe senescence detection in bone sections. But the paper does not establish that senescent cells are typically bone-embedded osteocytes across ageing and the cited disease states; the Discussion says the identity of senescent cells in its fracture callus remains unclear. (LLM, conf=0.85)

  cites [200] Saul, D. et al. Modulation of fracture healing by the transient accumulation of senescent cells. eLife 10, e69958 (2021). sourceExperimental — accuracy not yet measured

In the paper

“Expression of Cdkn2a is upregulated ~20-fold in mammary stromal cells of aged (25–32 months) mice230.”

What the sources say

• Supported

  The Results section (‘Aged MaSCs and stromal cells show an elevated inflammatory response’; page not provided) reports that the Cdkn2a locus was upregulated 20-fold in old stromal cells. Figure 4b identifies the old stromal-cell samples as coming from 26-month-old mice, within the cited 25–32-month age range. (LLM, conf=0.93)

  cites [230] Dong, Q. et al. Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential. Aging 8, 2754–2776 (2016). source

In the paper

“Moreover, they elicit components of the SASP such as IL-6 (refs. 242,243), Ccl2 (ref. 243) and Tgfb1 (ref. 243).”

What the sources say

• ?Not matched

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

  cites [242] Du, D. et al. Senotherapy protects against cisplatin-induced ovarian injury by removing senescent cells and alleviating DNA damage. Oxid. Med. Cell. Longev. 2022, 9144644 (2022).
• Supported

  The Results section ('Accumulation of senescent cells in murine ovaries after doxorubicin treatment'; page not available) reports significantly elevated mRNA for the SASP genes Il6, Mcp1 (Ccl2), and Tgfβ1 after doxorubicin treatment. This paper supports the doxorubicin portion of the citing sentence; the separate cisplatin citation is not being assessed here. (LLM, conf=0.90)

  cites [243] Gao, Y. et al. Increased cellular senescence in doxorubicin-induced murine ovarian injury: effect of senolytics. GeroScience 45, 1775–1790 (2023). source

In the paper

“Mouse models of melanoma and human nevi (both oncogene driven) show accumulation of SA-β-gal+–CDKN2A+ foci224,225.”

What the sources say

• Partly supported

  The Results section (“p16LUC Signals Cancer”; page unavailable) reports focal p16INK4a-promoter activity in an oncogene-driven mouse melanoma model. It does not establish that those foci are SA-β-gal-positive, and the cited paper does not report the claimed foci in human nevi. (LLM, conf=0.85)

  cites [224] Burd, C. E. et al. Monitoring tumorigenesis and senescence in vivo with a p16INK4a-luciferase model. Cell 152, 340–351 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  In the Nature article’s human-naevi results, all 23 congenital naevi tested showed SA-β-gal activity, and naevi contained p16INK4a-expressing cells (p16INK4a is encoded by CDKN2A). But p16INK4a staining was mosaic, and the paper does not establish an accumulation of uniformly double-positive foci. This source addresses the human-naevi part of the sentence, not the mouse-model part. (LLM, conf=0.86)

  cites [225] Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005). sourceExperimental — accuracy not yet measured

In the paper

“The secretion of SASP factors such as Ccl8 (ref. 239), CCL5 (ref. 241) and the pro-inflammatory related gene Crlf1 (ref. 239) also increases with age.”

What the sources say

• Partly supported

  The Results (Transcriptomic analysis; page unavailable) report that Ccl8 and Crlf1 expression increased with age in mouse ovaries, with RT-qPCR confirming the RNA-seq findings. The paper measured gene expression, not secretion of those factors. CCL5 is attached to a different citation in the citing sentence and is not assessed here. (LLM, conf=0.86)

  cites [239] Ansere, V. A. et al. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion. Mech. Ageing Dev. 194, 111425 (2021). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [241] Shen, L. et al. CCL5 secreted by senescent theca-interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis. J. Cell. Physiol. 234, 22554–22564 (2019). source

In the paper

“Repeated UVB exposure in human keratinocytes and mouse epidermis results in loss of LMNB1 (ref. 217).”

What the sources say

• Partly supported

  The Results section reports lamin B1 loss in human keratinocytes after UVB exposure and in mouse epidermis after irradiation for 10 consecutive days. The Methods describe a single irradiation of the keratinocyte cultures, so the source does not support repeated UVB exposure in human keratinocytes. (LLM, conf=0.88)

  cites [217] Wang, A. S., Ong, P. F., Chojnowski, A., Clavel, C. & Dreesen, O. Loss of lamin B1 is a biomarker to quantify cellular senescence in photoaged skin. Sci. Rep. 7, 15678 (2017). sourceExperimental — accuracy not yet measured

In the paper

“Other features of inflammation, such as macrophage crown-like structures230 and Cxcl1, Cxcl2, Cxcl16, Csf1, Csf3, Ccl5 and Il6 (ref. 231), are also elevated in mammary glands of aged mice.”

What the sources say

• Partly supported

  The Results section, “Aged MaSCs and stromal cells show an elevated inflammatory response” (page unavailable), reports increased inflammatory-related gene expression in old mammary cells, but our copy does not identify Cxcl1, Cxcl2, Cxcl16, Csf1, Csf3, Ccl5 or Il6 as elevated. The crown-like-structure finding is reported there too, although the citing sentence attaches a different reference to that finding. (LLM, conf=0.82)

  cites [230] Dong, Q. et al. Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential. Aging 8, 2754–2776 (2016). sourceExperimental — accuracy not yet measured
• Supported

  The Discussion reports increased production of the listed inflammatory cytokines in aged mammary glands; it prints “Csfs1,” while the Results section identifies increased Csf1 expression in aged myoepithelial and vascular endothelial cells. The separate citation for macrophage crown-like structures is not attributed to this source. Page numbers were not provided in our copy. (LLM, conf=0.91)

  cites [231] Li, C. M. et al. Aging-associated alterations in mammary epithelia and stroma revealed by single-cell RNA sequencing. Cell Rep. 33, 108566 (2020). source

In the paper

“Mouse models of UV radiation show increased expression of Mmp1, Mmp2 and Mmp3, and of other SASP factors such as TNF, IL-1β and IL-6 (refs. 220–223).”

What the sources say

• Partly supported

  Results §3.5 reports UVB-related differences in mouse-skin MMP expression, including MMP-2, but says MMP-3 did not differ significantly; it does not report a measurement of MMP-1 expression. Results §3.7 reports increased IL-6 and TNF-α levels in UVB-irradiated mice, but reports IL-12 rather than IL-1β. The cytokine findings concern protein levels, not gene expression. Page numbers are unavailable in our copy. (LLM, conf=0.89)

  cites [220] Jo, K. et al. An anthocyanin-enriched extract from vaccinium uliginosum improves signs of skin aging in UVB-induced photodamage. Antioxidants 9, 844 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results sections on UV-induced MMP-3 expression and ROS/NF-κB signaling (page not supplied) report higher MMP-3, TNF-α, IL-1β and IL-6 in UV-irradiated mouse skin than in controls. The paper does not report increased MMP-1 or MMP-2 expression in those mice; it mentions MMP-1 only in describing how it acts with MMP-3. It calls the cytokines inflammatory factors, not SASP factors. (LLM, conf=0.88)

  cites [221] Kong, S. et al. Preparation of cod skin collagen peptides/chitosan-based temperature-sensitive gel and its anti-photoaging effect in skin. Drug. Des. Devel. Ther. 17, 419–437 (2023). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion section on elevated MMP expression (page unavailable) reports increased MMPs in COL1A2-CCN1 mouse fibroblasts. But the mice were a genetic model of dermal aging, not a UV-radiation model, and the elevated enzymes reported were MMP-9, -10, -13, -24 and -27—not MMP-1, -2 or -3. The passages do not report increased TNF, IL-1β or IL-6 in these mice. (LLM, conf=0.86)

  cites [222] Quan, T. et al. Dermal fibroblast CCN1 expression in mice recapitulates human skin dermal aging. J. Invest. Dermatol. 141, 1007–1016 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section on TPA-induced senescence reports increased Mmp3 in mouse skin, supporting one factor in the claim, but the mice were treated with TPA, not UV radiation. The paper does not report increases in mouse-skin Mmp1, Mmp2, TNF or IL-1β; it explicitly reports no increase in Il-6 after TPA treatment (page unavailable in our copy). (LLM, conf=0.88)

  cites [223] Alimirah, F. et al. Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/42MAPK signaling. Cancer Res. 80, 3606–3619 (2020). sourceExperimental — accuracy not yet measured

In the paper

“In ovaries from mice of advanced reproductive age, cells classified as senescent are characterized by increased expression of Cdkn2a (refs. 238–240), Cdkn1a, Serpine1 and Hmgb1 (ref. 239).”

What the sources say

• Partly supported

  Table 1 (IHC and SA-β-gal staining; page unavailable) reports a 30.5-fold increase in p16INK4a expression in old mouse ovaries and staining in ovarian stroma, supporting the Cdkn2a portion. The paper does not establish that the ovarian cells were classified as senescent or report increased ovarian Cdkn1a, Serpine1, or Hmgb1. (LLM, conf=0.88)

  cites [238] Krishnamurthy, J. et al. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299–1307 (2004). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (“Senescence markers”; page not provided) report increased ovarian Cdkn1a, Cdkn2a, PAI-1/Serpine1 and HMGB1 expression in older mice. The Methods describe qPCR of ovarian samples, not expression measured specifically in cells classified as senescent. That cell-specific part of the claim is unsupported. (LLM, conf=0.88)

  cites [239] Ansere, V. A. et al. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion. Mech. Ageing Dev. 194, 111425 (2021). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section on aged ovarian microenvironments reports increased P16, a senescence marker, in granulosa cells from aged mice. The paper reports increased P21 in an in-vitro senescent human granulosa-cell model, not in aged mouse ovaries. Our copy does not report increased Serpine1 or Hmgb1 in those ovaries, or show that cells classified as senescent express all four markers. (LLM, conf=0.88)

  cites [240] Liu, M. et al. Cell-free fat extract improves ovarian function and fertility in mice with advanced age. Front. Endocrinol. 13, 912648 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Immunostaining reveals an increase with age of the frequency of ducts expressing the SASP factor COX2 (ref. 230).”

What the sources say

• Partly supported

  The Results (Figure 4c; page unavailable) report COX2-positive staining in a higher proportion of mammary ducts from old mice (48%) than young mice (10%). The Discussion links increased COX2 to inflammation and discusses cellular senescence, but the paper does not identify COX2 as a SASP factor. (LLM, conf=0.84)

  cites [230] Dong, Q. et al. Aging is associated with an expansion of CD49fhi mammary stem cells that show a decline in function and increased transformation potential. Aging 8, 2754–2776 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Chromatin aberrations reinforcing senescence are a common feature of skin senescence and are characterized by nuclear foci positive for TP53BP1 and PML211,212.”

What the sources say

• ?Could not verify

  The Results describe secretory profiles in senescent fibroblasts, including cells derived from neonatal foreskin, while the Discussion focuses on the senescence-associated secretory phenotype. Searches for TP53BP1, PML, and chromatin foci found no passage establishing that these foci are common in skin senescence or reinforce it. (LLM, conf=0.74)

  cites [211] Coppe, J. P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853–2868 (2008). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [212] Waldera Lupa, D. M. et al. Characterization of skin aging-associated secreted proteins (SAASP) produced by dermal fibroblasts isolated from intrinsically aged human skin. J. Invest. Dermatol. 135, 1954–1968 (2015). source

In the paper

“Additionally, these cells exhibit increased lysosomal content, as indicated by accumulation of lipofuscin aggregates (known as ‘aggresomes’)239 and by SA-β-gal staining in the stromal compartment241.”

What the sources say

• ?Could not verify

  Citation 241 is attached to the SA-β-gal staining in the stromal compartment, not to the lipofuscin finding cited as 239. The Discussion mentions β-galactosidase staining only as a comparator for lipofuscin staining; the passages found do not report SA-β-gal staining in ovarian stroma (searched for SA-β-gal, stromal compartment, and ovarian stroma). (LLM, conf=0.76)

  cites [239] Ansere, V. A. et al. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion. Mech. Ageing Dev. 194, 111425 (2021). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [241] Shen, L. et al. CCL5 secreted by senescent theca-interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis. J. Cell. Physiol. 234, 22554–22564 (2019). source

In the paper

“Single-cell expression and chromatin accessibility assays of post-menopausal human ovaries revealed that SASP-associated genes were expressed in stromal cells (SERPINE1, TIMP1, TIMP2, IGFBP2, IGFBP3 and IGFBP4), endothelial cells (IGFBP7) and perivascular endothelial cells (CDKN1A).”

What the sources say

• Partly supported

  The Results section on ligand-receptor interactions (page not provided) reports expression of SERPINE1, TIMP1, TIMP2 and IGFBP2/3/4 in ovarian stromal cells. The provided passages and searches for IGFBP7 and CDKN1A do not substantiate the claimed expression of those genes in endothelial and perivascular endothelial cells, respectively. (LLM, conf=0.86)

  cites [246] Lengyel, E. et al. A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing. Cell Rep. 41, 111838 (2022). sourceExperimental — accuracy not yet measured

In the paper

“The senescence‐associated tissue microenvironment promotes colon cancer formation in human colon epithelial cells and in human-derived colon organoids266.”

What the sources say

• Partly supported

  The Results section reports that senescent fibroblasts increased proliferation in colon epithelial cell lines and primary human colon organoids, and increased migration and invasion in the cell lines. It concludes that these effects *may* promote adenoma or colorectal cancer formation; the experiments described do not establish cancer formation in the cells or organoids as the citing sentence states. (LLM, conf=0.87)

  cites [266] Guo, Y. et al. Senescence-associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15. Aging Cell 18, e13013 (2019). sourceExperimental — accuracy not yet measured

In the paper

“SA-β-gal staining marks increased lysosomal content in 11 tissues”

In the paper

“Notably, CDKN2A and CDKN1A emerge as the predominantly reported markers for cell cycle arrest.”

In the paper

“Within the SASP, IL-6, TNF, IL-1α, IL-1β, SERPINE1 (also known as PAI-1) and TGFβ1 have been reported in more than ten tissues.”

In the paper

“Upregulation of the anti-apoptotic factor BCL2 was reported in four tissues.”

In the paper

“It is important to note that the presence of individual hallmarks is not sufficient to define the senescent state, as they can also be found in other cell states.”

In the paper

“However, there is currently no specific marker exclusively indicative of the senescent cell cycle arrest.”

In the paper

“Senescence can be transmitted to neighbouring cells, a phenomenon commonly known as secondary senescence.”

In the paper

“Beyond marker prioritization, we do not recommend the use of individual markers to determine the senescence state of cells because ample evidence exists of so-called false-positive senescence59 (Box 1).”

What the sources say

• ?Not checked — no full text of the sourcecites [59] Ogrodnik, M., Salmonowicz, H., Jurk, D. & Passos, J. F. Expansion and cell-cycle arrest: common denominators of cellular senescence. Trends Biochem. Sci. 44, 996–1008 (2019). source

In the paper

“Although less is known about hepatocyte senescence in humans than in mice, senescence-associated markers such as SA-β-gal staining have been identified in human cirrhotic livers160.”

What the sources say

• ?Not checked — no full text of the sourcecites [160] Wiemann, S. U. et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 16, 935–942 (2002). source

In the paper

“Lipofuscin is present in adult and old tubular cells in the medulla and in some cortical tubules in old kidneys151.”

What the sources say

• ?Not checked — no full text of the sourcecites [151] Melk, A. et al. Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int. 65, 510–520 (2004). source

In the paper

“The expression of PTGS1 and PTGS2 increases in ageing kidneys151.”

What the sources say

• ?Not checked — no full text of the sourcecites [151] Melk, A. et al. Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int. 65, 510–520 (2004). source

In the paper

“CDKN2A expression increases in renal arterial vascular smooth myocytes145,151.”

What the sources say

• ?Not checked — no full text of the sourcecites [145] Sis, B. et al. Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease. Kidney Int. 71, 218–226 (2007). source
• ?Not checked — no full text of the sourcecites [151] Melk, A. et al. Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney. Kidney Int. 65, 510–520 (2004). source

In the paper

“Mature human adipocytes undergo senescence in obesity and following hyperinsulinaemia challenge, displaying a premature senescence transcriptome and secretory profile including upregulated gene expression of CDKN2A, CDKN1A and CCND1 and downregulated expression of HMGB1 and HMGB2 (ref. 126).”

What the sources say

• ?Not checked — no full text of the sourcecites [126] Li, Q. et al. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nat. Med. 27, 1941–1953 (2021). source

In the paper

“Senescence is observed in several human and mouse kidney cell types during healthy ageing and nephropathy.”

In the paper

“By contrast, markers such as KL133, SIRT1134, SREBF1135, GDF15136, MDM2137, RRAD138 and GBP1139 are reported as negative regulators of cellular senescence in adipose tissue.”

What the sources say

• ?Not checked — no full text of the sourcecites [133] Ullah, M. & Sun, Z. Klotho deficiency accelerates stem cells aging by impairing telomerase activity. J. Gerontol. A Biol. Sci. Med. Sci. 74, 1396–1407 (2019). source
• ?Not checked — no full text of the sourcecites [134] Khanh, V. C. et al. Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1. Biochem. Biophys. Res. Commun. 500, 682–690 (2018). source
• ?Not checked — no full text of the sourcecites [135] Lee, G. et al. SREBP1c–PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity. Cell Metab. 34, 702–718.e5 (2022). source

In the paper

“Additionally, there is increased secretion of the SASP proteins CXCL8, SERPINE1, CXCL2 and MMP14.”

What the sources say

• ?Not checked — no full text of the sourcecites [126] Li, Q. et al. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nat. Med. 27, 1941–1953 (2021). source

In the paper

“WNT9A, which is induced in CDKN2A-expressing TECs in chronic kidney disease, co-localizes with MKI67-negative nuclei (indicative of non-proliferating cells)154.”

What the sources say

• ?Not checked — no full text of the sourcecites [154] Luo, C. et al. Wnt9a promotes renal fibrosis by accelerating cellular senescence in tubular epithelial cells. J. Am. Soc. Nephrol. 29, 1238–1256 (2018). source

In the paper

“Several of these factors were also found in human pancreatic islets from donors with type 1 diabetes184.”

What the sources say

• ?Not checked — no full text of the sourcecites [184] Thompson, P. J. et al. Targeted elimination of senescent β cells prevents type 1 diabetes. Cell Metab. 29, 1045–1060.e10 (2019). source

In the paper

“The accumulation of senescent cells is also linked with structural changes in the lung, broadly termed ‘senile emphysema’173.”

What the sources say

• ?Not checked — no full text of the sourcecites [173] Parikh, P. et al. Cellular senescence in the lung across the age spectrum. Am. J. Physiol. Lung Cell. Mol. Physiol. 316, L826–L842 (2019). source

In the paper

“In a mouse model of type 1 diabetes (NOD), the expression of several senescence markers such as Cdkn1a, Cdkn2a, H2ax, Il6, Mmp2, Serpine1, Il6 and Igfbp3 has been observed.”

What the sources say

• ?Not checked — no full text of the sourcecites [184] Thompson, P. J. et al. Targeted elimination of senescent β cells prevents type 1 diabetes. Cell Metab. 29, 1045–1060.e10 (2019). source

In the paper

“However, in neoplastic tissues, particularly in cases of low-grade dysplasia, four senescence markers (CDKN2A, CDKN2B, SA-β-gal activity and CBX5-γ) were detected197.”

What the sources say

• ?Not checked — no full text of the sourcecites [197] Miyasaka, Y. et al. Senescence in intraductal papillary mucinous neoplasm of the pancreas. Hum. Pathol. 42, 2010–2017 (2011). source

In the paper

“There is an association between the upregulation of GDF15, IL-6, CRP and TNFRSF1B in plasma with the susceptibility of the occurrence of interstitial lung abnormalities179.”

What the sources say

• ?Not checked — no full text of the sourcecites [179] Sanders, J. L. et al. The association of aging biomarkers, interstitial lung abnormalities, and mortality. Am. J. Respir. Crit. Care Med. 203, 1149–1157 (2021). source

In the paper

“Of the adult cell lineages of the pancreas, acinar cells show the highest plasticity, allowing them to undergo dedifferentiation or transdifferentiation to an embryonic progenitor phenotype expressing ductal markers in a process known as acinar-to-ductal metaplasia188,189.”

What the sources say

• ?Not checked — no full text of the sourcecites [188] Pinho, A. V. et al. Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis. Gut 60, 958–966 (2011). source
• ?Not checked — no full text of the sourcecites [189] Rooman, I. & Real, F. X. Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation and development? Gut 61, 449–458 (2012). source

In the paper

“CDKN2A is the predominant marker associated with senescence in the lung.”

In the paper

“Interestingly, these markers decreased in abundance during the transition to intraductal papillary mucinous neoplasm.”

What the sources say

• ?Not checked — no full text of the sourcecites [197] Miyasaka, Y. et al. Senescence in intraductal papillary mucinous neoplasm of the pancreas. Hum. Pathol. 42, 2010–2017 (2011). source

In the paper

“In a study involving 158 cases of intraductal papillary mucinous neoplasms and 10 normal controls, neither SA-β-gal activity nor SAHF formation was observed in the normal controls.”

What the sources say

• ?Not checked — no full text of the sourcecites [197] Miyasaka, Y. et al. Senescence in intraductal papillary mucinous neoplasm of the pancreas. Hum. Pathol. 42, 2010–2017 (2011). source

In the paper

“Photodamage markers include the accumulation of 53BP1, H2AJ and mtDNA4977 (a common mtDNA deletion)216.”

What the sources say

• ?Not checked — no full text of the sourcecites [216] Berneburg, M. et al. Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin. J. Invest. Dermatol. 122, 1277–1283 (2004). source

In the paper

“Furthermore, in a mouse model of premature ovarian insufficiency, SAHF formation was observed in the ovary, indicated by increased H3K9me3 and CBX5 staining and higher HMGA1 and HMGA2 protein expression245.”

What the sources say

• ?Not checked — no full text of the sourcecites [245] Su, X. et al. Effect of Jiajian Guishen Formula on the senescence-associated heterochromatic foci in mouse ovaria after induction of premature ovarian aging by the endocrine-disrupting agent 4-vinylcyclohexene diepoxide. J. Ethnopharmacol. 269, 113720 (2021). source

In the paper

“In a genetic mouse model of accelerated ovarian ageing, Cdkn2a, Cdkn1a, Il1a and Il1b levels were elevated244.”

What the sources say

• ?Not checked — no full text of the sourcecites [244] Zhu, J. et al. Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice. Free. Radic. Biol. Med. 193, 511–525 (2022). source

In the paper

“In response to UVB, the SASP from primary human melanocytes has elevated levels of secreted IL-6, CXCL8, CCL1, CCL2 and HMGB1 (ref. 219).”

What the sources say

• ?Not checked — no full text of the sourcecites [219] Zhang, K., Anumanthan, G., Scheaffer, S. & Cornelius, L. A. HMGB1/RAGE mediates UVB-induced secretory inflammatory response and resistance to apoptosis in human melanocytes. J. Invest. Dermatol. 139, 202–212 (2019). source

In the paper

“The early development of UV radiation-caused solar lentigines (liver spots) features the accumulation of melanocytes expressing CDKN2A, CDKN1A and p53, as well as increased TNF218.”

What the sources say

• ?Not checked — no full text of the sourcecites [218] Goorochurn, R. et al. Biological processes in solar lentigo: insights brought by experimental models. Exp. Dermatol. 25, 174–177 (2016). source

In the paper

“A substantial research challenge arises from the overlap of senescence markers with conditions or experimental models associated with inflammation or fibrosis. This overlap complicates the establishment of cause and consequence, as the presence of these markers may signify various biological processes occurring simultaneously (Box 1).”

In the paper

“The placenta can also undergo accelerated or premature senescence in adverse pregnancy outcomes such as pre-eclampsia and fetal growth restriction264.”

What the sources say

• ?Not checked — no full text of the sourcecites [264] Farfan-Labonne, B., Leff-Gelman, P., Pellon-Diaz, G. & Camacho-Arroyo, I. Cellular senescence in normal and adverse pregnancy. Reprod. Biol. 23, 100734 (2023). source

In the paper

“This genetic programme suggests that components of placental developmental senescence are recapitulated in other cellular senescence contexts.”

What the sources say

• ?Not checked — no full text of the sourcecites [263] Liu, Z. et al. Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging. Dev. Cell 57, 1347–1368.e12 (2022). source