Cellular senescence in ageing: from mechanisms to therapeutic opportunities

In the paper

“genetic and pharmacological clearance of p16-expressing senescent cells ameliorated heart functions in aged mice140.”

What the sources say

• Disputed

  In Results, ‘Senescent-cell clearance reduces cardiac hypertrophy and fibrosis’ (Figs 7G, EV5B–C), genetic clearance reduced hypertrophy and fibrosis in aged mice but did not change ejection fraction. The same Results section (Figs 8E–G) says pharmacological treatment with navitoclax had no significant impact on cardiac function. The paper reports improved cardiac remodelling, not improved heart function. (LLM, conf=0.91)

  Checked by a reasoning model — may be wrong.

  cites [140] Anderson, R. et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. https://doi.org/10.15252/embj.2018100492 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Similarly, transforming growth factor-β improves liver regeneration on injury by blocking paracrine senescence in neighbouring uninjured hepatocytes188.”

What the sources say

• Disputed

  The Introduction says macrophage-derived TGFβ drives the spread of senescence between hepatocytes. The Results section on TGFβR1 inhibition reports that blocking TGFβ signaling—not TGFβ itself—reduced hepatocellular senescence and improved regeneration after acute liver injury. Page numbers are not provided in our copy. (LLM, conf=0.94)

  Checked by a reasoning model — may be wrong.

  cites [188] Bird, T. G. et al. TGFbeta inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci. Transl Med. https://doi.org/10.1126/scitranslmed.aan1230 (2018). sourceExperimental — accuracy not yet measured

In the paper

“If DNA damage persists, it causes prolonged DDR signalling and protracted proliferative arrest in the form of cellular senescence22”

What the sources say

• Supported

  The Introduction (page not supplied) says that when DNA damage remains unrepaired, cells enter cellular senescence with a persistently active DDR. It also describes senescence as a permanent cell-cycle arrest, matching the claim's protracted proliferative arrest. (LLM, conf=0.93)

  cites [22] Fumagalli, M., Rossiello, F., Mondello, C. & d’Adda di Fagagna, F. Stable cellular senescence is associated with persistent DDR activation. PLoS ONE 9, e110969 (2014). source

In the paper

“Some DDR factors accumulate at sites of DNA damage and form cytologically detectable nuclear foci composed of extended chromatin modification events, such as the phosphorylation of histone H2AX, and the proteins associated with them, including MDC1, 53BP1 and the activated form of the kinase ataxia telangiectasia mutated (ATM)21”

What the sources say

• Partly supported

  The DNA-damage signaling and cell-cycle checkpoints section (page unavailable) describes H2AX phosphorylation on chromatin flanking double-strand breaks, recruitment of DDR factors, and ATM recruitment and activation at breaks. It does not identify MDC1 or 53BP1 among those factors or state that they form cytologically detectable nuclear foci with activated ATM. (LLM, conf=0.85)

  cites [21] Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 1071–1078 (2009). sourceExperimental — accuracy not yet measured

In the paper

“Senescent cells have increased resistance to apoptotic cell death owing to upregulation of cell survival pathways, including the BCL-2 family of antiapoptotic proteins, even on exogenous stress exposure14,15”

What the sources say

• Supported

  The Results section reports that senescent fibroblasts survived TNF-α treatment and UV irradiation better than control cells, and that antiapoptotic BCL-2 family proteins were upregulated. The Discussion identifies BCL-family activation as a mechanism of their increased resistance to apoptosis. (LLM, conf=0.93)

  cites [14] 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
• Partly supported

  In the passage labeled Abstract (page unavailable), the paper reports increased BCL-xL in senescent cells and experiments suggesting that BCL-2 and BCL-xL protect them from apoptosis. It does not establish greater resistance to apoptotic death than normal cells after exogenous stress exposure; it also reports no increase in BCL-2 expression. (LLM, conf=0.83)

  cites [15] 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

In the paper

“The recent demonstration that persistent DDR foci observed in cultured senescent cells contain unrepaired DSBs23 supports the notion that cellular senescence is akin to prolonged checkpoint activation”

What the sources say

• Supported

  In Introduction, Results, and Discussion (page unavailable), the authors report that DI-PLA detected DNA breaks at persistent DDR foci in cultured senescent cells. They conclude that these foci correspond to genuine, unrepaired double-strand breaks. (LLM, conf=0.95)

  cites [23] Galbiati, A., Beausejour, C. & d’Adda di Fagagna, F. A novel single-cell method provides direct evidence of persistent DNA damage in senescent cells and aged mammalian tissues. Aging Cell 16, 422–427 (2017). source

In the paper

“Inhibition of DDR signalling kinases (ATM, ATR, CHK1 and CHK2) allows senescent cells to re-enter the cell cycle7,24,25”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006). source
• ?Not checked — no full text of the sourcecites [24] d’Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003). This study demonstrates that the activation of the DDR pathways by critically short telomeres is key in the enforcement of cellular senescence. source
• Partly supported

  The Conclusions (page unavailable) identify ATM, ATR, Chk1 and Chk2 as required for the senescence program and say that interfering with the DDR can bypass oncogene-induced senescence. But the authors report rescuing that response only when the Rb pathway was also inactivated. The paper does not establish that inhibiting those kinases makes already-senescent cells re-enter the cell cycle. (LLM, conf=0.87)

  cites [25] Mallette, F. A. & Ferbeyre, G. The DNA damage signaling pathway connects oncogenic stress to cellular senescence. Cell Cycle 6, 1831–1836 (2007). sourceExperimental — accuracy not yet measured

In the paper

“Rather, SAHF enforce a DDR-resistant heterochromatin structure that restrains DDR signalling52”

What the sources say

• Supported

  The Results section reports that, in oncogene-induced senescent cells, SAHF exclude DNA-damage sensors and other DDR factors. Perturbing heterochromatin allows those factors into previously excluded regions and increases DDR signalling, supporting the claim in this oncogene-induced context. Page numbers were not provided. (LLM, conf=0.91)

  cites [52] Di Micco, R. et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat. Cell Biol. 13, 292–302 (2011). sourceExperimental — accuracy not yet measured

In the paper

“the reactivation of transposable elements also contributes to mediate the non-cell-autonomous functions of senescent cells as detailed later62”

What the sources say

• Supported

  The Abstract reports that LINE-1 elements become active during senescence and trigger an interferon response that helps maintain the senescence-associated secretory phenotype (SASP). The “Consequences of L1 activation” section further reports that blocking interferon signaling reduces late SASP markers, supporting the claimed contribution to senescent cells’ non-cell-autonomous functions. (LLM, conf=0.91)

  cites [62] De Cecco, M. et al. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566, 73–78 (2019). source

In the paper

“Although initially PTEN loss-induced cellular senescence was not associated with DDR activation40, it was later found to be associated with hyperproliferation, DDR engagement and cellular senescence in vivo41”

What the sources say

• Supported

  This source supports the clause attached to citation 40: Pten-loss-induced senescence was not associated with DDR activation. The Figure 2 discussion (p. 5) reports senescence in Pten-null mouse prostates without a significant increase in the DDR marker phospho-γ-H2AX and concludes that DDR is not engaged. The later finding about hyperproliferation and DDR is attached to citation 41, not this source. (LLM, conf=0.94)

  cites [40] Alimonti, A. et al. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J. Clin. Invest. 120, 681–693 (2010). source
• Supported

  The Introduction (page not provided) contrasts earlier reports of no observed hyperproliferation or DDR activation with this study’s findings. It reports that PTEN ablation stimulated proliferation in adult mouse prostatic luminal cells for several months, induced replication stress and a DDR, and was followed by senescence-like growth arrest. (LLM, conf=0.92)

  cites [41] Parisotto, M. et al. PTEN deletion in luminal cells of mature prostate induces replication stress and senescence in vivo. J. Exp. Med. 215, 1749–1763 (2018). source

In the paper

“a core SASP programme comprising mainly proinflammatory interleukin-6 (IL-6), CXC chemokine ligand 8 (CXCL8, hereafter named IL-8) and monocyte chemoattractant protein 1 (MCP1; also known as CCL2) was reported in all types of in vitro-generated senescent cells75”

What the sources say

• Partly supported

  The Discussion describes IL-6, IL-8 and MCP-1 as core SASP features, and the Results report substantial overlap among the senescent fibroblast and epithelial cells studied (page numbers unavailable). But the paper lists other core factors, notes differences between cell types, and only suggests—not establishes—that a conserved programme occurs in any cell undergoing senescence. It therefore does not support ‘mainly’ those three factors or ‘all types’ as stated. (LLM, conf=0.86)

  cites [75] 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

In the paper

“Genome-wide analysis of H3 Lys4 trimethylation, H3 Lys27 trimethylation and H3 Lys27 acetylation in senescent cells has also revealed the dynamic acquisition and depletion of large-scale chromatin domains that have been proposed to regulate the expression of key senescence downstream effectors68–72”

What the sources say

• Partly supported

  The Results (pages not available in our copy) report genome-wide gains and losses of large H3K4me3 and H3K27me3 domains, with changes associated with expression of senescence-related genes. The study analyzed those two modifications, but did not report a genome-wide analysis of dynamic H3K27ac domains; it mentions H3K27ac only when identifying active enhancers. (LLM, conf=0.88)

  cites [68] Shah, P. P. et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape. Genes Dev. 27, 1787–1799 (2013). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction (page unavailable) discusses chromatin rearrangement in senescent cells and its correlation with gene-expression changes, while the Discussion focuses on lamin B1 loss. Searches for H3K4me3, H3K27me3, H3K27ac, genome-wide analysis, and large-scale chromatin domains found no passage in our copy addressing the claimed acquisition or depletion of histone-mark domains. (LLM, conf=0.77)

  cites [69] Freund, A., Laberge, R. M., Demaria, M. & Campisi, J. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell 23, 2066–2075 (2012). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Discussion proposes that lamin B1 might affect chromatin organization and gene expression, and the methods describe a targeted senescence-gene expression assay. Our copy does not report a genome-wide analysis of H3K4me3, H3K27me3, or H3K27ac, or the acquisition and depletion of large-scale domains; searches for those marks and domain changes found no supporting passage. No page numbers were available in the indexed passages. (LLM, conf=0.74)

  cites [70] Shimi, T. et al. The role of nuclear lamin B1 in cell proliferation and senescence. Genes Dev. 25, 2579–2593 (2011). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results sections on enhancer remodeling and the SASP transcriptional profile report genome-wide H3K27ac changes in senescent IMR90 cells, including gains and losses at super-enhancers associated with senescence-related gene expression. The Methods describe analysis of H3K27ac and H3K4me1, but not the claimed H3K4me3 or H3K27me3 analyses. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [71] Tasdemir, N. et al. BRD4 connects enhancer remodeling to senescence immune surveillance. Cancer Discov. 6, 612–629 (2016). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction describes large regions of H3K4me3 and H3K27me3 enrichment and H3K27me3 depletion in senescent cells, citing earlier work. The Results report genome-wide H3K27ac analysis that identifies senescence-activated and -deactivated enhancers, and links activated super-enhancers to senescence-associated gene expression. Together, these passages support the broad claim; the trimethylation findings are reported as prior work rather than new analyses in this paper. (LLM, conf=0.86)

  cites [72] Sen, P. et al. Histone acetyltransferase p300 induces de novo super-enhancers to drive cellular senescence. Mol. Cell 73, 684–698 e688 (2019). sourceExperimental — accuracy not yet measured

In the paper

“Dysfunctional mitochondria may play an important role in senescence establishment, as depletion of mitochondrial sirtuins, a group of evolutionarily conserved proteins that regulate ageing across different species, as well as selective chemical inhibition of mitochondrial function, triggers senescence47”

What the sources say

• Supported

  The Results section, “Mitochondrial SIRTs Suppress Senescent Phenotypes” (page not available), reports that depletion of mitochondrial SIRT3 or SIRT5 induced senescence. “Mitochondrial Dysfunction and Senescent Phenotypes” (page not available) reports that treatment with the mitochondrial electron-transport inhibitors rotenone or antimycin A also induced senescence. (LLM, conf=0.94)

  cites [47] Wiley, C. D. et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 23, 303–314 (2016). source

In the paper

“Loss of nuclear lamina can lead to the release of cytosolic chromatin fragments (CCFs) in the cytoplasm of senescent cells58–60”

What the sources say

• Supported

  The Results section, “Formation of CCF is associated with nuclear-to-cytoplasmic chromatin blebbing,” links lamin B1 down-regulation in senescent cells to nuclear-envelope permeability and loss of chromatin to the cytoplasm. The Discussion explicitly describes dispersal of those fragments as CCFs. The paper supports the claim as a possible consequence, rather than establishing that loss of the entire nuclear lamina is the sole cause. (LLM, conf=0.91)

  cites [58] Ivanov, A. et al. Lysosome-mediated processing of chromatin in senescence. J. Cell Biol. 202, 129–143 (2013). source
• Supported

  In the paper’s main text (indexed under Abstract; page unavailable), HRasV12-induced senescence is associated with reduced Lamin B1 at the nuclear lamina and cytoplasmic chromatin fragments. The same section reports that an intervention disrupting LC3–Lamin B1 interaction delayed the appearance of those fragments, supporting the hedged claim that lamina loss can lead to their release. (LLM, conf=0.86)

  cites [59] Dou, Z. et al. Autophagy mediates degradation of nuclear lamina. Nature 527, 105–109 (2015). source
• Supported

  The Abstract states that loss of Lamin B1 compromises nuclear-envelope integrity and that chromatin-containing membrane blebs in senescent cells eventually partition into the cytoplasm as CCF. It also reports that reducing Lamin B1 increases CCF, while overexpressing it impairs CCF generation. (LLM, conf=0.94)

  cites [60] Dou, Z. et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550, 402–406 (2017). This study demonstrates that cytoplasmic chromatin in senescent and cancer cells activates the innate immunity through the cGAS–STING pathway. source

In the paper

“oncogene-induced ROS, generated by NADPH oxidases, can induce cellular senescence by boosting the initial hyperproliferative phase associated with altered DNA replication and DNA damage accumulation45”

What the sources say

• Supported

  The Abstract states that oncogenic Ras-induced ROS are produced in a Rac1- and Nox4-dependent manner and that ROS fuel hyperproliferation, eventually activating the DNA damage response. The Abstract also links the initial hyperproliferative phase to altered DNA replication and subsequent senescence; the Results section describes that hyperproliferation as intrinsically genotoxic. Page numbers are not provided in our copy. (LLM, conf=0.92)

  cites [45] Ogrunc, M. et al. Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation. Cell Death Differ. 21, 998–1012 (2014). source

In the paper

“Persistent DDR activation occurs also at telomeres that are not critically shortened, in non-dividing cells exposed to exogenous genotoxic treatments and in non-dividing ageing cells, because repair is much less efficient when DSBs are localized within telomeres35–37”

What the sources say

• Supported

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

  cites [35] Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355–365 (2012). source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [36] Hewitt, G. et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat. Commun. 3, 708 (2012). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [37] Bae, N. S. & Baumann, P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol. Cell 26, 323–334 (2007). source

In the paper

“oncogene-induced senescent cells and late replicatively senescent fibroblasts exhibit a marked increase in chromatin accessibility at the nucleosomal level, with most of the open chromatin regions mapping to regulatory elements and repeats66,67”

What the sources say

• Supported

  For the oncogene-induced senescence portion of this two-citation sentence, the Results (Altered chromatin accessibility in RIS and NIS) report a marked increase in accessibility in RIS cells and place the majority of opened regions in enhancer, intergenic, intronic, and repeat regions. The Discussion explicitly describes the increase as occurring at the nucleosome scale. (LLM, conf=0.91)

  cites [66] Parry, A. J. et al. NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence. Nat. Commun. 9, 1840 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page unavailable) describes relatively more open chromatin at repeats and other gene-poor regions in replicatively senescent cells, with changes most evident after prolonged senescence. It also describes reduced accessibility at active regulatory regions. This paper does not establish the claim for oncogene-induced senescence or show that most open regions map to regulatory elements and repeats. (LLM, conf=0.88)

  cites [67] De Cecco, M. et al. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12, 247–256 (2013). sourceExperimental — accuracy not yet measured

In the paper

“mitochondrial dysfunction-associated senescence (MiDAs), which is characterized by a distinct phenotype, exhibits a unique cell-non-autonomous programme that is potentially responsible for the altered metabolism and aberrant adipocyte differentiation observed in aged animals47”

What the sources say

• Partly supported

  The Discussion (page unavailable) describes MiDAS as a distinct senescence response with a distinct secretory phenotype. Results (‘MiDAS in POLG Mice’; page unavailable) show that conditioned medium from mitochondrially impaired cells blocked adipogenesis in cell culture, supporting a potential cell-non-autonomous effect. The paper does not establish that this programme accounts for altered metabolism or aberrant adipocyte differentiation observed in normally aged animals; its in-vivo evidence comes from progeroid mice. (LLM, conf=0.84)

  cites [47] Wiley, C. D. et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 23, 303–314 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Chromatin loosening at genomic repeats results in increased expression levels of transposable elements, which are normally epigenetically silenced and dormant in unstressed cells67”

What the sources say

• Supported

  The Abstract states that retrotransposon chromatin becomes more open in senescent cells, leading to increased transcription. The Discussion says retrotransposons are normally in repressed heterochromatin and expressed at very low levels in unstressed cells. The claim reflects those findings in the paper's senescence context. (LLM, conf=0.92)

  cites [67] De Cecco, M. et al. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell 12, 247–256 (2013). source

In the paper

“Senescence-associated heterochromatin foci (SAHF) are spatially organized heterochromatic domains that can be detected as dense 4′,6-diamidino-2-phenylindole (DAPI)-positive nuclear structures that are enriched in repressive chromatin marks and proteins, including trimethylated histone H3 Lys9 (H3K9me3), heterochromatin protein 1 (HP1), high mobility group protein A (HMGA) factors, histone variant”

What the sources say

• Partly supported

  The Results (page not provided) identify SAHF as DNA foci seen with DAPI staining and report enrichment of lysine-9-methylated histone H3 and HP1. The passages do not specify trimethylation, and the searched passages do not support enrichment of HMGA factors, macroH2A, HIRA, or ASF1A. (LLM, conf=0.87)

  cites [49] Narita, M. et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113, 703–716 (2003). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [50] Zhang, R. et al. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev. Cell 8, 19–30 (2005). source
• Partly supported

  The Introduction describes SAHFs as DAPI-dense foci, and the Results (‘Multilayer Structure of Chromatin in SAHFs’; page not provided) show spatially organized H3K9me3-rich regions containing HP1γ. The paper also identifies HMGA1 as a structural component. Our copy does not establish enrichment of macroH2A, HIRA, or ASF1A in SAHFs; searches for those terms found no supporting passages. (LLM, conf=0.86)

  cites [51] Chandra, T. et al. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol. Cell 47, 203–214 (2012). sourceExperimental — accuracy not yet measured

In the paper

“persistent DDR activation at telomeres, which is a trigger of cellular senescence, can occur both upon telomere shortening in proliferating cells and upon telomeric DNA damage also in non-proliferating (quiescent or terminally differentiated) cells, independently of telomere length38”

What the sources say

• Partly supported

  The Results (‘Telomere deprotection triggers both strands’ transcription’; page unavailable) report DDR activation after experimental telomere deprotection, supporting the general link between dysfunctional telomeres and DDR. Our copy does not establish the claimed routes through shortening in proliferating cells or damage in non-proliferating cells, nor that this occurs independently of telomere length and triggers senescence. (LLM, conf=0.82)

  cites [38] Rossiello, F. et al. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs. Nat. Commun. 8, 13980 (2017). sourceExperimental — accuracy not yet measured

In the paper

“There is evidence in support of a reciprocal influence between nuclear DNA damage and mitochondrial dysfunction48”

What the sources say

• Partly supported

  The Results sections on PGC-1β-dependent biogenesis and ROS-driven DNA damage foci (page not provided) show influence in both directions: DNA damage response increases mitochondrial mass, while mitochondrial biogenesis and ROS help maintain DNA damage foci. The paper does not establish that nuclear DNA damage causes mitochondrial dysfunction specifically; the mitochondrial change it demonstrates is increased biogenesis. (LLM, conf=0.84)

  cites [48] Correia-Melo, C. et al. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J. 35, 724–742 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Another chromatin feature of senescent cells is the unfolding of constitutive heterochromatin domains characterized mainly by distension of pericentromeric satellite sequences, which was observed in different species and following different modes of senescence induction57”

What the sources say

• Supported

  The Introduction describes decondensation of peri/centromeric satellite heterochromatin in senescent cells, across a variety of senescence models and in both human and mouse cells. The Discussion likewise calls satellite distension a distinguishing mark in all models studied. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites [57] Swanson, E. C., Manning, B., Zhang, H. & Lawrence, J. B. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J. Cell Biol. 203, 929–942 (2013). source

In the paper

“Furthermore, JAK inhibitors alleviated frailty in aged mice99.”

What the sources say

• Supported

  In the section on physical activity in aged, frail mice (Fig. 8), the paper reports that 10 weeks of JAK1/2 inhibitor treatment improved activity, endurance, grip strength, and coordination compared with vehicle treatment. The Discussion describes these findings as alleviation of frailty in aged mice. (LLM, conf=0.94)

  cites [99] 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

In the paper

“In this context, JAK/STAT inhibitors were effective in reprogramming the SASP to enhance chemotherapy and T cell-mediated clearance of cancer senescent cells98.”

What the sources say

• Supported

  The Summary (p. 2) reports that a JAK2 inhibitor combined with docetaxel reprogrammed the SASP and improved treatment efficacy in Pten-null tumors. The treatment results (p. 6) report T-cell infiltration around senescent cells and a marked reduction in senescent cells, supporting the claim about T-cell-associated clearance in this model. (LLM, conf=0.90)

  cites [98] Toso, A. et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9, 75–89 (2014). source

In the paper

“Exosomes were recently identified as key mediators of the paracrine senescence effects of SASP as well as of its protumorigenic properties83,84”

What the sources say

• Partly supported

  The Discussion (page not available) reports that small extracellular vesicles mediate paracrine senescence, supporting the first part of the claim. The Introduction says SASP can promote cancer proliferation, but the passages do not establish that these vesicles mediate that protumorigenic effect. (LLM, conf=0.88)

  cites [83] Borghesan, M. et al. Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein IFITM3. Cell Rep. 27, 3956–3971 e3956 (2019). sourceExperimental — accuracy not yet measured
• Partly supported

  Section 4.2 says exosomes are SASP components that can mediate paracrine signaling, and describes their pro-tumorigenic role as emerging. Section 4.1 says SASP factors can induce senescence in neighbouring cells, but our copy does not establish that exosomes are key mediators of that specific effect. The claim also states their pro-tumorigenic role more definitively than the review does. (LLM, conf=0.85)

  cites [84] Jakhar, R. & Crasta, K. Exosomes as emerging pro-tumorigenic mediators of the senescence-associated secretory phenotype. Int. J. Mol. Sci. https://doi.org/10.3390/ijms20102547 (2019). sourceExperimental — accuracy not yet measured

In the paper

“temporal changes in NOTCH1 activity during senescence have been reported to modulate the composition of SASP.”

What the sources say

• Supported

  The Introduction states that NOTCH1 regulates SASP composition through a temporal switch between TGF-β and pro-inflammatory secretomes. The Results section reports changing NOTCH1 activity during senescence and concludes that it determines the balance between those secretory profiles. (LLM, conf=0.94)

  cites [94] Hoare, M. et al. NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat. Cell Biol. 18, 979–992 (2016). source

In the paper

“The JAK2–STAT3 pathway activates a subset of SASP factors with immunosuppressive properties in a model of senescence induced by PTEN loss.”

What the sources say

• Supported

  The Discussion (p. 10) says that inactivating Jak2/Stat3 reprograms the SASP of PTEN-null senescent tumors, reducing cytokines involved in recruiting and activating immunosuppressive MDSCs. The results (p. 6) likewise report that Stat3 inactivation lowers specific cytokines and switches the response from immunosuppression to active immune surveillance. (LLM, conf=0.92)

  cites [98] Toso, A. et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9, 75–89 (2014). source

In the paper

“overexpression of EZH2 prevents entry into OIS through a variety of mechanisms, including DDR regulation and inhibition of the SASP gene expression programme106.”

What the sources say

• Partly supported

  The Results section “EZH2 Suppresses Entry into Oncogene-Induced Senescence” reports that ectopic EZH2 strongly alleviated entry into OIS and broadly alleviated SASP-gene induction; it does not say entry was completely prevented. The paper links EZH2 depletion to DNA damage and a DDR, but the cited passages do not establish DDR regulation as a demonstrated mechanism by which EZH2 overexpression suppresses OIS. (LLM, conf=0.84)

  cites [106] Ito, T., Teo, Y. V., Evans, S. A., Neretti, N. & Sedivy, J. M. Regulation of cellular senescence by polycomb chromatin modifiers through distinct DNA damage- and histone methylation-dependent pathways. Cell Rep. 22, 3480–3492 (2018). sourceExperimental — accuracy not yet measured

In the paper

“a comprehensive unbiased quantitative proteomic characterization of SASP led to the identification of additional and diverse SASP effectors, released as soluble molecules or in exosomes79–81 with a set of components previously reported to be enriched in human plasma during ageing and age-associated diseases82”

What the sources say

• Partly supported

  The Results section (‘Identification of senescent secretome specific proteins’; page unavailable) reports LC-MS/MS analysis of mesenchymal stromal cell secretomes and identifies 11 proteins exclusive to the senescent phenotypes. Our copy does not establish that these proteins were released in exosomes or previously found enriched in human plasma during ageing or age-associated diseases. (LLM, conf=0.86)

  cites [79] Ozcan, S. et al. Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses. Aging 8, 1316–1329 (2016). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion describes an unbiased quantitative proteomic analysis of diverse SASP components, and the Methods describe separating soluble proteins from exosomes/EVs. The Results section on aging and disease biomarkers reports overlap between newly identified soluble SASP factors and human plasma markers of aging. It does not establish that those factors were enriched in human plasma during age-associated diseases; it discusses disease biomarkers as potential applications. (LLM, conf=0.86)

  cites [80] 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
• ?Not checked — no full text of the sourcecites [81] 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
• Partly supported

  The Results (Association of proteins with chronological age; page unavailable) report that 21 of 72 measured SASP proteins were associated with age in plasma, with significant enrichment overall. The Discussion links some age-associated proteins to age-related conditions, but this study of healthy humans does not establish that the SASP components were enriched in plasma during those diseases. The claims about comprehensive SASP characterization and exosomal release are attached to other citations, not this one. (LLM, conf=0.84)

  cites [82] Tanaka, T. et al. Plasma proteomic signature of age in healthy humans. Aging Cell 17, e12799 (2018). sourceExperimental — accuracy not yet measured

In the paper

“ATM was found to regulate expression of SASP genes indirectly by mediating the removal of the histone variant macroH2A1.1 from SASP genes in response to DNA damage and oncogenic stress87”

What the sources say

• Partly supported

  The Results section on ATM-mediated SASP gene repression reports that ATM activity triggers removal of macroH2A1 from SASP genes during oncogene-induced senescence, through a pathway involving DNA-damage signaling. The paper separately shows that macroH2A1.1 can stimulate SASP expression, but the ATM-removal experiments identify macroH2A1 generally, not the macroH2A1.1 splice variant specifically; that specificity is unsupported. (LLM, conf=0.85)

  cites [87] Chen, H. et al. MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol. Cell 59, 719–731 (2015). sourceExperimental — accuracy not yet measured

In the paper

“SASP not only includes proinflammatory molecules but also enzymes involved in ECM remodelling, such as matrix metalloproteinases (MMPs)77, serine/cysteine proteinase inhibitors (SERPINs)78 and tissue inhibitors of metalloproteinases (TIMPs)79”

What the sources say

• Supported

  Citation 77 is attached to the MMP example, not the separately cited SERPINs and TIMPs. The Discussion identifies inflammatory cytokines and several MMPs as SASP factors, and the Results section on MMP gene clusters reports MMP expression and secretion in senescent cells. (LLM, conf=0.92)

  cites [77] Coppe, J. P. et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE 5, e9188 (2010). source
• ?Not checked — no full text of the sourcecites [78] Eren, M. et al. PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc. Natl Acad. Sci. USA 111, 7090–7095 (2014). source
• Partly supported

  The Discussion (page unavailable) identifies PAI-1 (SERPINE1) in senescent secretomes and says it prevents proteolysis of IGFBP3. That supports the citation attached to SERPINs, but the paper does not establish that SERPINE1 remodels the extracellular matrix; it discusses ECM remodelling chiefly in relation to MMPs. (LLM, conf=0.83)

  cites [79] Ozcan, S. et al. Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses. Aging 8, 1316–1329 (2016). sourceExperimental — accuracy not yet measured

In the paper

“However, a recent chemical screen identified a small molecule that degrades BRD4 and has senolytic activity104.”

What the sources say

• Partly supported

  The Results section reports that ARV825 degrades BRD4 and has strong senolytic activity. However, the high-throughput screen identified BET inhibitors; ARV825 was tested afterward to confirm and extend the screening results, not identified as a screen hit. (LLM, conf=0.88)

  cites [104] Wakita, M. et al. A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells. Nat. Commun. 11, 1935 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Moreover, BRD4 was shown to positively regulate telomere elongation in murine and human cultures105.”

What the sources say

• Supported

  The Introduction identifies BRD4 as a positive regulator of telomere length. The Abstract reports that BRD4 inhibitors blocked telomere elongation in mouse cells, and the Results and Discussion report telomere shortening after BRD4 inhibition in both mouse and human cells in culture. (LLM, conf=0.92)

  cites [105] Wang, S. et al. BRD4 inhibitors block telomere elongation. Nucleic Acids Res. 45, 8403–8410 (2017). source

In the paper

“Ageing is one of the factors that is consistently associated with an increase in DDR in proliferating and non-proliferating cells, thus contributing significantly to the accumulation of senescent cells with age35,89”

What the sources say

• Partly supported

  The Abstract reports more DDR-positive cells with age across tissues and cell types, and the Results section on physiological ageing in primates reports persistent DDR foci in non-dividing neurons and hepatocytes. The Discussion proposes that persistent telomeric DDR leads to senescence, but does not establish that increased DDR contributes significantly to the accumulation of senescent cells with age. (LLM, conf=0.84)

  cites [35] Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355–365 (2012). sourceExperimental — accuracy not yet measured
• Partly supported

  In “DSBs, DSB processing and aging” (page unavailable), the paper reports that DNA-damage-associated γH2AX foci increase with age in multiple tissues, including fibroblasts and brain, and in senescent cells. The Abstract says DSB-triggered DDR can lead to senescence. But the paper does not establish that DDR activity consistently increases in both proliferating and non-proliferating cells or that this significantly causes senescent-cell accumulation; “DSB processing and repair as a function of age” also describes declines in some damage responses. (LLM, conf=0.85)

  cites [89] White, R. R., Vijg, J. & Do, D. N. A. Double-strand breaks drive aging? Mol. Cell 63, 729–738 (2016). sourceExperimental — accuracy not yet measured

In the paper

“SASP gene expression is temporally dynamic100, and temporal changes in NOTCH1 activity during senescence have been reported to modulate the composition of SASP.”

What the sources say

• Supported

  The Results and Discussion report that genes encoding SASP factors showed significant heterogeneity across time points and cell types (Figure 3D). The authors also state that time after senescence induction is important in determining the SASP. This supports the cited clause about temporally dynamic SASP gene expression; the separate NOTCH1 clause is not attributed to this source. (LLM, conf=0.94)

  cites [100] Hernandez-Segura, A. et al. Unmasking transcriptional heterogeneity in senescent cells. Curr. Biol. 27, 2652–2660 e2654 (2017). source

In the paper

“Furthermore, increased nuclear pore density during OIS, which is key to establish SAHF, regulates SASP expression by mediating heterochromatin reorganization111.”

What the sources say

• Partly supported

  The Results and Discussion sections report that nuclear pore density rises during OIS, that reducing it decreases SAHF formation, and that disrupting pores or SAHFs impairs the SASP (pages not supplied). The paper supports heterochromatin reorganization as the link, but says it cannot completely rule out a separate effect of nuclear pores on SASP activation; the claim states that mechanism more definitively than the source does. (LLM, conf=0.83)

  cites [111] Boumendil, C., Hari, P., Olsen, K. C. F., Acosta, J. C. & Bickmore, W. A. Nuclear pore density controls heterochromatin reorganization during senescence. Genes Dev. 33, 144–149 (2019). sourceExperimental — accuracy not yet measured

In the paper

“persistent DDR signalling is often required to initiate inflammatory cytokine secretion86”

What the sources say

• Supported

  The Abstract states that inflammatory cytokine secretion occurred only after persistent DNA damage signalling was established, not after transient responses. It also says that initiating the cytokine response required the DDR proteins ATM, NBS1 and CHK2. This supports the citing sentence’s qualified wording, “often required.” (LLM, conf=0.94)

  cites [86] Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009). This study demonstrates that persistent DDR activation controls SASP induction in senescent cells. source

In the paper

“Incomplete DNA repair may further contribute to the accumulation of DNA lesions and DDR activation as well as to the widespread chromatin changes seen in different cell types and at the organismal level during ageing90,91”

What the sources say

• Partly supported

  In “Persistent DNA damage: a driving force of aging” (page unavailable), the paper says unrepaired lesions can persist and activate the DDR, and that limited repair in aged hematopoietic stem cells leads to gradual DNA-damage accumulation. Our copy does not link incomplete repair to widespread chromatin changes across cell types or at the organismal level during aging. (LLM, conf=0.88)

  cites [90] Ou, H. L. & Schumacher, B. DNA damage responses and p53 in the aging process. Blood 131, 488–495 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  “DNA DSB repair declines with age” reports less efficient repair in aged tissues, and “Shared responsibilities: factors involved in DNA repair, chromatin and aging” links DNA damage to broad chromatin and transcriptional changes. The copy does not establish that incomplete repair causes sustained DDR activation, so that part of the claim remains unsupported. Page numbers were not available in the indexed passages. (LLM, conf=0.84)

  cites [91] Gorbunova, V. & Seluanov, A. DNA double strand break repair, aging and the chromatin connection. Mutat. Res. 788, 2–6 (2016). sourceExperimental — accuracy not yet measured

In the paper

“accumulation of DNA replication stress in HSCs from aged mice was linked to limited yet detectable HSC senescence, unbalanced haematopoietic differentiation and myeloid skewing127.”

What the sources say

• Supported

  The paper reports heightened replication stress in HSCs from old mice and describes senescence in rare cases (Abstract; no page number available). It also reports loss of lymphoid potential and reduced lymphoid output after transplantation, consistent with unbalanced differentiation and myeloid skewing (Abstract; Extended Data Figures 1 and 7). (LLM, conf=0.87)

  cites [127] Flach, J. et al. Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature 512, 198–202 (2014). source

In the paper

“In a mouse model of Alzheimer disease, transcriptomic analyses of tau-containing neurons indicated an expression profile consistent with cellular senescence136.”

What the sources say

• Partly supported

  The Results section on tau transgenic mice reports that hippocampal gene-expression patterns after neurofibrillary tangle formation were enriched for senescence-associated regulators. But the mouse analysis used hippocampal expression data, not transcriptomic analyses of isolated tau-containing neurons; the Results section describes that neuron-specific analysis for postmortem human AD tissue. (LLM, conf=0.86)

  cites [136] Musi, N. et al. Tau protein aggregation is associated with cellular senescence in the brain. Aging Cell 17, e12840 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Lineage tracing experiments in vivo in irradiated mice confirmed the induction of expression of differentiation markers in the subventricular zone of the brain, normally populated by neural stem cells128.”

What the sources say

• Supported

  In Results, under “DNA Damage In Vivo Leads to Astrocytic Differentiation of NSCs in the SVZ,” the authors describe permanently labeling SOX2-expressing neural stem cells before cranial irradiation. Three days later, labeled cells in the subventricular zone often expressed the astrocytic differentiation markers GFAP and S100β; the section also reports significantly greater marker overlap than in non-irradiated controls. (LLM, conf=0.94)

  cites [128] Schneider, L. et al. DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAK-STAT. Stem Cell Rep. 1, 123–138 (2013). source

In the paper

“Senescent cells, especially when persisting for extended periods in culture or in vivo, display a profound activation of type I interferon response and downstream targets.”

What the sources say

• Supported

  The ‘Activation of L1 and interferon in cellular senescence’ section reports high IFN-α and IFN-β1 levels in late senescent cultures and describes IFN-I induction as a later phase of senescence. The ‘Activation of L1 in human and mouse tissues’ section reports increased IFN-I response genes in old mouse tissues and in an in vivo model of induced senescence; the Extended Data identifies IRF7 and OAS1 among the response genes examined. No page numbers are available in our copy. (LLM, conf=0.87)

  cites [62] De Cecco, M. et al. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566, 73–78 (2019). source

In the paper

“The inflammasome, a multiprotein complex comprising caspase 1 and key regulators of the defence mechanisms against pathogens117, and Toll-like receptors, which regulate the inflammasome, have been reported to promote maturation and secretion of SASP factors during OIS73,118.”

What the sources say

• Partly supported

  The section “Activation of the inflammasome controls SASP production” (page unavailable) reports that cells undergoing OIS secrete mature IL-1α and IL-1β and show caspase-1 activity, supporting the inflammasome portion of the claim. The retrieved passages do not establish that Toll-like receptors regulate the inflammasome or promote SASP-factor maturation and secretion during OIS. (LLM, conf=0.86)

  cites [73] 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
• Supported

  The Results section (‘TLR2 controls the activation of the SASP in OIS’; page not supplied) reports that TLR2 and TLR10 knockdown reduced mature active IL-1β and its accumulation in conditioned media during OIS. The Introduction explains that inflammasome activation cleaves and activates IL-1β, while the Results identify inflammasome activation as a key step in SASP induction. (LLM, conf=0.90)

  cites [118] Hari, P. et al. The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Sci. Adv. 5, eaaw0254 (2019). source

In the paper

“Conversely, obesity in mice was associated with the expression of senescence markers in neurons of specific parts of the brain135.”

What the sources say

• Supported

  The Results section reports significantly more neurons bearing the senescence marker TAF in the basomedial amygdala of high-fat-diet mice. It also reports an increase in senescent NeuN-positive cells in the hypothalamus compared with lean mice. No page number was provided in our copy. (LLM, conf=0.93)

  cites [135] Ogrodnik, M. et al. Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Cell Metab. 29, 1061–1077.e1068 (2019). source

In the paper

“Thus, DNA damage-induced cellular senescence can coincide with cell differentiation128,129.”

What the sources say

• Supported

  The Discussion states that DNA damage in neural stem cells leads to cellular senescence while promoting astrocytic differentiation. It also describes astrocytic differentiation of senescent cells, directly supporting the claim that the two can coincide. (LLM, conf=0.94)

  cites [128] Schneider, L. et al. DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAK-STAT. Stem Cell Rep. 1, 123–138 (2013). source
• Supported

  The Results report that irradiated, surviving neural stem cells showed senescence markers and that more than 80% expressed an astrocytic marker. The Discussion interprets these findings as evidence that severe DNA damage can promote astrocytic differentiation alongside senescence, while noting that the cells may have an intermediate phenotype. Page numbers are unavailable in our copy. (LLM, conf=0.92)

  cites [129] Zou, Y. et al. Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation. Biochem. Biophys. Res. Commun. 426, 100–105 (2012). source

In the paper

“A distinct form of cellular senescence occurs in the mammalian developing embryo and in the placenta to control growth and patterning131,132,142,143.”

What the sources say

• Partly supported

  The Summary (p. 1) describes senescence as a normal developmental mechanism throughout the embryo, including signaling centers involved in patterning; the Introduction (p. 2) also identifies a role in tissue development and patterning. The cited paper does not establish the claim about senescence in the placenta; a search for “placenta” found no matching passage in our copy. (LLM, conf=0.86)

  cites [131] Storer, M. et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119–1130 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract and Introduction report a distinct, developmentally programmed form of senescence in mammalian embryos. The Abstract links it to tissue remodeling and developmental abnormalities, supporting a role in embryonic development. The passages do not establish senescence in the placenta or a placental role in growth and patterning. (LLM, conf=0.87)

  cites [132] Munoz-Espin, D. et al. Programmed cell senescence during mammalian embryonic development. Cell 155, 1104–1118 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page unavailable) show senescence markers in human placental syncytiotrophoblast cells, and the Discussion links their senescence to placental function during embryonic development. The paper does not show senescence in the developing embryo itself or establish that it controls embryonic growth and patterning; it also says the reason senescence is necessary in placental development remains to be determined. (LLM, conf=0.85)

  cites [142] Chuprin, A. et al. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes Dev. 27, 2356–2366 (2013). sourceExperimental — accuracy not yet measured

In the paper

“Although not extensively investigated, and mainly studied in neurons, evidence is emerging that cellular senescence can be associated with terminally differentiated cells133,134.”

What the sources say

• ?Not checked — no full text of the sourcecites [133] Sapieha, P. & Mallette, F. A. Cellular senescence in postmitotic cells: beyond growth arrest. Trends Cell Biol. 28, 595–607 (2018). source
• Supported

  The Discussion reports that mature postmitotic neurons develop a phenotype resembling typical cellular senescence across multiple markers. This supports the qualified claim that evidence of senescence-associated features is emerging in terminally differentiated cells, particularly neurons. (LLM, conf=0.93)

  cites [134] 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). source

In the paper

“Similarly, in amphibians, cellular senescence occurs at specific steps during development to shape body growth144.”

What the sources say

• Supported

  The Discussion (page unavailable) says senescence occurs in specific amphibian embryonic structures during well-defined time windows and is required for pronephros degeneration and appropriate cement-gland development. The Results (page unavailable) also report altered cement-gland and mouth development when senescent cells were eliminated, supporting the claim that senescence helps shape development. (LLM, conf=0.88)

  cites [144] Davaapil, H., Brockes, J. P. & Yun, M. H. Conserved and novel functions of programmed cellular senescence during vertebrate development. Development 144, 106–114 (2017). source

In the paper

“Senescence can be regarded as a stress response that evolved to perform essential and beneficial functions141 (FIG. 3).”

What the sources say

• Partly supported

  The Overview describes senescence as a response to cellular stress and identifies beneficial short-term roles in tumor suppression and wound healing. The Abstract calls it an essential mechanism, but says only that its pro-survival phenotype *may* have evolved to aid short-term wound healing; it does not establish that senescence itself evolved to perform beneficial functions generally. (LLM, conf=0.84)

  cites [141] Burton, D. G. & Krizhanovsky, V. Physiological and pathological consequences of cellular senescence. Cell. Mol. Life Sci. 71, 4373–4386 (2014). sourceExperimental — accuracy not yet measured

In the paper

“persistent telomeric DNA damage in cardiomyocytes drives a senescence phenotype characterized by induction of p16 and p21 and a non-canonical SASP programme that contributes to cardiac hypertrophy and fibrosis140.”

What the sources say

• Supported

  The Abstract (page not provided) states that persistent telomeric damage in cardiomyocytes activates p21 and p16 and produces a non-canonical secretory phenotype that is pro-fibrotic and pro-hypertrophic. The Discussion (page not provided) identifies secreted factors that promote myofibroblast activation and cardiomyocyte hypertrophy. (LLM, conf=0.94)

  cites [140] Anderson, R. et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. https://doi.org/10.15252/embj.2018100492 (2019). source

In the paper

“Notably, in mouse embryonic stem cells, a p53-induced programme is associated with transcriptional activation of a differentiation programme and the repression of pluripotent stem cell genes130.”

What the sources say

• Supported

  The Results section ('p53-activated genes and p53-repressed genes have distinct functions') reports that p53 activates differentiation-associated genes and represses genes required to maintain mouse embryonic stem-cell status. The Abstract likewise describes activation of differentiation-associated genes and repression of ES cell-enriched genes in response to DNA damage. (LLM, conf=0.94)

  cites [130] Li, M. et al. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol. Cell 46, 30–42 (2012). source

In the paper

“it was reported that aberrant activation of the cGAS–STING pathway could be linked to the downregulation of DNases (for example, DNase 2 and TREX1) that are normally devoted to cytoplasmic DNA degradation, resulting in cytosolic accumulation of nuclear DNA during senescence establishment115.”

What the sources say

• Supported

  The Introduction says DNase2 and TREX1 normally remove nuclear DNA exported to the cytoplasm, but their downregulation in senescent cells appears to allow that DNA to accumulate and aberrantly activate cGAS–STING. The Discussion likewise links DNA damage response to this accumulation and pathway activation, while qualifying the DNases' contribution as partial. (LLM, conf=0.94)

  cites [115] Takahashi, A. et al. Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells. Nat. Commun. 9, 1249 (2018). source

In the paper

“during ageing terminally differentiated cells can accumulate persistent DNA damage and DDR markers35,89”

What the sources say

• Supported

  The Results section reports that persistent DDR foci accumulate with age in baboon hippocampal neurons, which it identifies as terminally differentiated cells. The Discussion also describes persistent telomeric DNA damage during ageing. Page numbers were not supplied in our copy. (LLM, conf=0.93)

  cites [35] Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355–365 (2012). source
• Partly supported

  In “DSBs, DSB processing and aging” (page unavailable), the paper reports that persistent γH2AX foci, a DNA-damage-response marker, increase with age in several cells and tissues, including brain and liver. It also says unrepaired DSBs may accumulate with age, but does not establish that the observed foci represent unrepaired DNA damage or specifically identify terminally differentiated cells as the affected population. (LLM, conf=0.82)

  cites [89] White, R. R., Vijg, J. & Do, D. N. A. Double-strand breaks drive aging? Mol. Cell 63, 729–738 (2016). sourceExperimental — accuracy not yet measured

In the paper

“in salamanders, senescent cells have been associated with limb regeneration150.”

What the sources say

• Supported

  The Results section, “Induction of cellular senescence during salamander limb regeneration” (page not provided), reports a significant rise in senescent cells during intermediate stages of newt limb regeneration and similar observations in axolotls. This supports the claimed association without implying that senescent cells cause regeneration. (LLM, conf=0.94)

  cites [150] Yun, M. H., Davaapil, H. & Brockes, J. P. Recurrent turnover of senescent cells during regeneration of a complex structure. eLife https://doi.org/10.7554/eLife.05505 (2015). sourceExperimental — accuracy not yet measured

In the paper

“By contrast, during cancer development associated with accumulation of senescent cells, SASP can recruit immature myeloid cells to promote tumorigenesis in a paracrine manner160,161.”

What the sources say

• ?Not checked — no full text of the sourcecites [160] Di Mitri, D. et al. Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer. Nature 515, 134–137 (2014). source
• Supported

  The Results section reports that SASP-mediated CCL2–CCR2 signaling caused immature myeloid-cell accumulation and promoted tumor growth in mice. The Discussion explains that these cells inhibit NK-cell activity, allowing existing liver tumors to grow; the effect is indirect, not a direct stimulation of tumor cells by SASP. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [161] Eggert, T. et al. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 30, 533–547 (2016). source

In the paper

“Recently, atherosclerotic plaques from LDL receptor-null mice were found to accumulate high amounts of SA-β-Gal and p16-positive endothelial cells, vascular smooth muscle cells and macrophages.”

What the sources say

• Partly supported

  The paper reports SA β-Gal–positive lesions and elevated p16Ink4a transcripts in plaque-rich aortic arches of Ldlr−/− mice. Its plaque microscopy passage (Fig. 1A; page unavailable) identifies three senescent cell types resembling endothelial cells, VSMCs, and macrophages, but explicitly says their origins cannot be accurately determined. The claim overstates those cell identities as definitive. (LLM, conf=0.86)

  cites [175] 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

In the paper

“Cellular senescence contributes to the maintenance of the structure and the function of tissues following injury.”

What the sources say

• Partly supported

  The Discussion reports that senescence of activated hepatic stellate cells limits fibrosis after liver damage and describes it as a homeostatic mechanism that helps tissue return to its pre-damaged state. It says this mechanism may apply to other wound-healing responses, but does not establish maintenance of tissue structure and function after injury generally. (LLM, conf=0.85)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [146] Kim, K. H., Chen, C. C., Monzon, R. I. & Lau, L. F. Matricellular protein CCN1 promotes regression of liver fibrosis through induction of cellular senescence in hepatic myofibroblasts. Mol. Cell. Biol. 33, 2078–2090 (2013). source

In the paper

“Moreover, induction of a senescence programme limits fibrosis progression in the pancreas148.”

What the sources say

• Partly supported

  The Introduction (page unavailable) proposes a role for senescence in regulating pancreatic fibrogenesis, and the Discussion (page unavailable) describes it as a possible component of pancreatic wound healing. But the rat study reports that senescent cells correlated with the extent of fibrosis; it does not show that inducing senescence limits fibrosis progression in the pancreas. (LLM, conf=0.86)

  cites [148] Fitzner, B. et al. Senescence determines the fate of activated rat pancreatic stellate cells. J. Cell Mol. Med. 16, 2620–2630 (2012). sourceExperimental — accuracy not yet measured

In the paper

“Among these cell types, NK cells, T cells and macrophages can physically interact with senescent cells in pathological and physiological conditions131,132,145,150,153–156.”

What the sources say

• Partly supported

  The developmental-limb findings (p. 7) show macrophages surrounding senescent cells, and the Discussion (p. 10) describes immune-mediated clearance. This supports the macrophage component in a physiological setting, but the paper does not identify NK- or T-cell interactions with senescent cells or establish physical interactions by all three cell types in both pathological and physiological conditions. (LLM, conf=0.87)

  cites [131] Storer, M. et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119–1130 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  The “Clearance of Senescent Cells and Compensatory Mechanisms” section reports that macrophages surround senescent embryonic tubules and describes macrophage clearance of senescent tumor cells. It does not establish the claimed physical interactions involving NK cells or T cells. Page numbers were not available in our copy. (LLM, conf=0.86)

  cites [132] Munoz-Espin, D. et al. Programmed cell senescence during mammalian embryonic development. Cell 155, 1104–1118 (2013). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section, “Senescent stellate cells are selectively targeted by NK cells” (page unavailable), shows NK cells attacking senescent cells in vitro. The Results section, “Immune cells are found in proximity to senescent cells in fibrotic livers” (page unavailable), reports macrophages and activated lymphocytes near senescent-marker-positive cells in diseased mice, but does not identify those lymphocytes as T cells or establish physical contact by T cells or macrophages. It does not demonstrate these interactions under physiological conditions. (LLM, conf=0.87)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. sourceExperimental — accuracy not yet measured

In the paper

“Senescence immunosurveillance is also essential to limit pathological fibrotic conditions and ageing20,145,151,157.”

What the sources say

• Supported

  The Results section reports that old perforin-deficient mice had more than twice the fibrotic area of controls in several tissues. The Discussion states that perforin-mediated elimination of senescent cells limits their accumulation during aging and links impaired clearance to age-related pathology and shorter lifespan. Together, these passages support the claim in the mouse models studied. (LLM, conf=0.93)

  cites [20] Ovadya, Y. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat. Commun. 9, 5435 (2018). source
• Partly supported

  The Results section ('Senescent stellate cells are selectively targeted by NK cells'; page unavailable) reports that inhibiting NK-cell activity delayed clearance of senescent cells and left significantly more liver fibrosis, supporting a role for immune surveillance in limiting fibrosis. The Discussion (page unavailable) only speculates that declining immune function may contribute to senescent-cell accumulation in aged tissues; it does not establish that senescence immunosurveillance is essential to limit ageing or fibrotic conditions generally. (LLM, conf=0.87)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [151] Sagiv, A. & Krizhanovsky, V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology 14, 617–628 (2013). source

In the paper

“Specialized SASP chemokines are able to attract distinct subsets of immune cells, including NK cells, neutrophils, dendritic cells, monocytes/macrophages, B cells and T cells75,151,152.”

What the sources say

• Partly supported

  The Discussion passage says that SASP cytokines and chemokines might contribute to infiltration by innate immune cells in senescing mouse tumors. It does not identify distinct recruited subsets or support the full list of NK cells, neutrophils, dendritic cells, monocytes/macrophages, B cells, and T cells. Page information is unavailable in our copy. (LLM, conf=0.87)

  cites [75] 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 [151] Sagiv, A. & Krizhanovsky, V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology 14, 617–628 (2013). source
• Partly supported

  The sections “Senescent cells as a source of chronic inflammation” and “Multiple roles of the SASP” say that the SASP includes chemokines and can stimulate immune clearance, including clearance by NK cells. “Chronic inflammation might propel basic aging processes” also describes senescent-cell cytokines as attractors of innate immune cells. The paper does not establish that specialized SASP chemokines attract each of the other listed subsets—neutrophils, dendritic cells, monocytes/macrophages, B cells and T cells. (LLM, conf=0.87)

  cites [152] Freund, A., Orjalo, A. V., Desprez, P. Y. & Campisi, J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol. Med. 16, 238–246 (2010). sourceExperimental — accuracy not yet measured

In the paper

“The surveillance and clearance of senescent cells by the immune system is necessary in order to limit tumorigenesis in premalignant lesions and following cancer therapy155,156,159.”

What the sources say

• Partly supported

  The passages labeled Abstract report that suppressing innate immune cells delayed clearance of murine liver tumours after p53 reactivation, supporting a role for immune surveillance in that setting. The paper says clearance may reinforce tumour suppression in premalignant settings or after senescence-promoting treatment; it does not establish that immune clearance is necessary to limit tumorigenesis in those broader settings. No page numbers are provided in our copy. (LLM, conf=0.86)

  cites [155] 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
• ?Not checked — no full text of the sourcecites [156] Kang, T. W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547–551 (2011). source
• Partly supported

  In the paper’s discussion of combination-treated KRAS-mutant lung tumors (section labeled Abstract; page unavailable), NK-cell depletion prevented tumor regression and reduced the treatment’s survival benefit, supporting a role for immune clearance after this therapy. The discussion of premalignant cells concerns RB-mediated restraint of proliferation, not a demonstrated need for immune clearance of senescent cells in premalignant lesions. The claim also generalizes beyond the specific therapy and mouse models studied. (LLM, conf=0.88)

  cites [159] Ruscetti, M. et al. NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination. Science 362, 1416–1422 (2018). sourceExperimental — accuracy not yet measured

In the paper

“in liver fibrosis, a condition associated with scarring of the liver and decrease in its function, senescence limits the proliferation and expansion of ECM-producing activated hepatic stellate cells145,146. This response limits the progression of the pathology following liver damage.”

What the sources say

• Supported

  The Discussion states that senescence arrests activated hepatic stellate cells, limiting expansion of the cells that produce the fibrotic scar. It also reports that this limits fibrotic tissue accumulation following liver damage. The supplied passages have section labels but no page numbers. (LLM, conf=0.93)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. source
• ?Not checked — no full text of the sourcecites [146] Kim, K. H., Chen, C. C., Monzon, R. I. & Lau, L. F. Matricellular protein CCN1 promotes regression of liver fibrosis through induction of cellular senescence in hepatic myofibroblasts. Mol. Cell. Biol. 33, 2078–2090 (2013). source

In the paper

“The homeostatic function of senescent cells is dependent on their elimination by the immune system, once their beneficial functions have been performed145,151.”

What the sources say

• Partly supported

  The Results section reports that reducing NK-cell activity left more senescent stellate cells and more fibrosis, supporting immune clearance as a contributor to fibrosis resolution. The Discussion describes this as a homeostatic mechanism but cautions that not all senescent cells are immune targets. The paper does not establish that homeostatic function generally depends on clearance, or that clearance occurs only after beneficial functions are complete. (LLM, conf=0.84)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [151] Sagiv, A. & Krizhanovsky, V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology 14, 617–628 (2013). source

In the paper

“During wound healing, the SASP component PDGF-AA accelerates wound closure12.”

What the sources say

• Supported

  The Discussion identifies PDGF-AA as a SASP factor whose early secretion accelerates cutaneous wound healing. The Results section, “Senescence-Associated PDGF-A Promotes Optimal Wound Closure through Myofibroblast Differentiation,” reports that topical PDGF-AA restored delayed wound-closure kinetics in mice depleted of senescent cells. (LLM, conf=0.94)

  cites [12] Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014). source

In the paper

“Moreover, shortened telomere length, observed during ageing, correlates with metabolic and cardiac dysfunctions171,172.”

What the sources say

• ?Not checked — no full text of the sourcecites [171] D’Mello, M. J. et al. Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ. Cardiovasc. Genet. 8, 82–90 (2015). source
• Partly supported

  The Introduction (page unavailable) reports that shorter leukocyte telomere length is associated with atherosclerosis risk and, in some studies, higher BMI. The Results report telomere shortening over time, but the paper does not establish correlations with metabolic and cardiac dysfunction as broadly stated. Its Discussion also cautions against assuming that adult telomere shortening explains aging-related disease. (LLM, conf=0.84)

  cites [172] Benetos, A. et al. Tracking and fixed ranking of leukocyte telomere length across the adult life course. Aging Cell 12, 615–621 (2013). sourceExperimental — accuracy not yet measured

In the paper

“In vitro studies demonstrated that cellular senescence is a potent cell-autonomous barrier for transcription factor-mediated reprograming using OCT4, SOX2, KLF4 and MYC (commonly referred to as OSKM), in a manner similar to its role in tumour suppression181–183.”

What the sources say

• Partly supported

  The Abstract says that senescence may be a barrier to reprogramming in cultured cells and compares p53’s effects on reprogramming and tumour formation. But it says the senescence mechanism is suggested rather than demonstrated, and does not establish senescence specifically as a cell-autonomous barrier to OSKM-mediated reprogramming. (LLM, conf=0.84)

  cites [181] Krizhanovsky, V. & Lowe, S. W. Stem cells: The promises and perils of p53. Nature 460, 1085–1086 (2009). sourceExperimental — accuracy not yet measured
• Supported

  The introduction describes oncogene-induced senescence as tumor-suppressive and identifies reprogramming-induced senescence as an initial barrier that limits reprogramming efficiency. The Results and Discussion report that expressing Oct4, Sox2, Klf4, and c-Myc in cultured fibroblasts induces senescence-like growth arrest, and that alleviating senescence improves reprogramming. (LLM, conf=0.90)

  cites [182] Banito, A. et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev. 23, 2134–2139 (2009). source
• Partly supported

  The paper’s main text (indexed under Abstract; page unavailable) reports that loss of Ink4a/Arf improves reprogramming, including when c-Myc is added to Oct4, Sox2 and Klf4. Its concluding passage draws a parallel between the locus’s roles as a barrier to malignancy and to de-differentiation. The experiments establish a barrier involving this senescence-associated locus, but do not directly demonstrate that cellular senescence itself is the cell-autonomous barrier claimed. (LLM, conf=0.82)

  cites [183] Li, H. et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136–1139 (2009). sourceExperimental — accuracy not yet measured

In the paper

“Macrophages with senescence-like features have also been identified in lesions from patients with cell histiocytoses, haematological neoplasms associated with oncogene activation characterized by multiorgan dissemination of highly inflamed, p16-positive myeloid cells177,178.”

What the sources say

• Partly supported

  The Introduction (page unavailable) describes Erdheim–Chester disease as a multisystem histiocytosis involving tissue-infiltrating macrophages with an activating BRAF mutation. Figure 1 shows p16-positive infiltrating histiocytes, and Figure 2 links that marker to oncogene-induced senescence and inflammation. The paper does not establish Erdheim–Chester disease as a haematological neoplasm; its Abstract says whether the disease is inflammatory or clonal has long been debated. (LLM, conf=0.86)

  cites [177] Cavalli, G., Biavasco, R., Borgiani, B. & Dagna, L. Oncogene-induced senescence as a new mechanism of disease: the paradigm of erdheim-chester disease. Front. Immunol. 5, 281 (2014). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [178] Cangi, M. G. et al. BRAFV600E-mutation is invariably present and associated to oncogene-induced senescence in Erdheim-Chester disease. Ann. Rheum. Dis. 74, 1596–1602 (2015). source

In the paper

“More recently, clinically approved antibiotics have been reported to have senolytic activity towards DNA-damage induced senescent cells through metabolic changes217.”

What the sources say

• Partly supported

  The Results report that azithromycin and roxithromycin preferentially eliminated BrdU-induced senescent human fibroblasts. The Abstract and Discussion report metabolic changes with azithromycin, but say these changes could explain its senolytic activity; they do not establish that the antibiotics kill cells through those changes. (LLM, conf=0.88)

  cites [217] Ozsvari, B., Nuttall, J. R., Sotgia, F. & Lisanti, M. P. Azithromycin and roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts. Aging 10, 3294–3307 (2018). sourceExperimental — accuracy not yet measured

In the paper

“These two mouse models have greatly accelerated our understanding of whether senescent cells contribute to ageing and age-related diseases, at least in model organisms, for numerous diseases, including Parkinson disease196, Alzheimer disease197,198, atherosclerosis175, idiopathic pulmonary fibrosis199, chronic obstructive pulmonary disease200 and osteoarthritis201.”

What the sources say

• Supported

  The citation is attached to Parkinson disease, not to every condition in the list. In Results, “Depleting Senescent Cells Abrogates PQ-Induced Neuropathology” (page unavailable), the paper uses p16-3MR mice to test whether senescent cells contribute to Parkinson-like neuropathology and reports that depleting those cells prevented paraquat-induced neuropathology and motor deficits. (LLM, conf=0.91)

  cites [196] 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). source
• Partly supported

  The main text (page not available) reports that clearing senescent cells with INK-ATTAC in PS19 mice prevented tau pathology, neurodegeneration and cognitive decline. That supports this citation’s contribution to the Alzheimer-disease example, but the study tests a tauopathy model, not Alzheimer disease as a whole, and does not test p16-3MR or the other listed diseases. (LLM, conf=0.82)

  cites [197] Bussian, T. J. et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562, 578–582 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion reports that removing senescent cells with senolytic treatment improved learning and memory in APP/PS1 Alzheimer’s disease mice, supporting the Alzheimer’s disease portion of the cited sentence. But the Methods describe a p16-ZsGreen reporter rather than INK-ATTAC or p16-3MR, and the Discussion proposes testing selective genetic elimination in Alzheimer’s disease mice as future work. This source therefore does not show that those two mouse models produced the Alzheimer’s disease finding attributed to it. (LLM, conf=0.89)

  cites [198] Zhang, P. et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model. Nat. Neurosci. 22, 719–728 (2019). sourceExperimental — accuracy not yet measured
• Supported

  Citation 175 is attached to atherosclerosis, not to the other diseases in the list. The supplied passage on senescent-cell clearance (labelled Abstract in our copy; no page given) reports reduced plaque burden with p16-3MR and says the result was reproduced with INK-ATTAC, supporting the claim that these models advanced understanding of senescent cells’ role in atherosclerosis. (LLM, conf=0.93)

  cites [175] Childs, B. G. et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354, 472–477 (2016). source

In the paper

“Administration of proxofim (a peptide) promotes senolysis by interfering with the binding of p53 to forkhead box protein O4 (FOXO4)206.”

What the sources say

• Partly supported

  The Results section reports that the peptide FOXO4-DRI competes with FOXO4 for p53 binding and selectively induces apoptosis in senescent cells. Our copy does not name the peptide proxofim or establish that proxofim is FOXO4-DRI, so it does not verify that part of the claim. (LLM, conf=0.84)

  cites [206] Baar, M. P. et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169, 132–147 e116 (2017). sourceExperimental — accuracy not yet measured

In the paper

“In addition, specific SASP components, either soluble or in extracellular vesicles186, can induce senescence in a paracrine manner — which includes DDR activation73,83.”

What the sources say

• Partly supported

  The sections “Multiple components of the SASP mediate paracrine senescence” and “Paracrine senescence is a stable arrest mediated by secreted factors” support induction by secreted factors. “Paracrine senescence resembles a full senescence response” reports increased DNA damage in neighboring cells, but does not explicitly establish activation of the DNA-damage response. The extracellular-vesicle qualifier has its own citation (186) in the citing sentence and is not attributed to this paper. (LLM, conf=0.82)

  cites [73] 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
• Supported

  Citation 186 is attached to the extracellular-vesicle part of the sentence, not to DDR activation, which has separate citations. The Discussion (page not provided) states that small extracellular vesicles mediate paracrine senescence; the Results report a senescent signature after cells were treated with vesicles from senescent cells. (LLM, conf=0.94)

  cites [83] Borghesan, M. et al. Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein IFITM3. Cell Rep. 27, 3956–3971 e3956 (2019). source
• Supported

  Citation 186 is attached to the extracellular-vesicle part of the sentence. The Abstract identifies EphA2 as a component enriched in small extracellular vesicles secreted by senescent cells, and the Results describe those vesicles as contributing to a SASP effect. The claims about inducing paracrine senescence and DDR activation are accompanied by other citations, not this one. (LLM, conf=0.90)

  cites [186] Takasugi, M. et al. Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat. Commun. 8, 15729 (2017). source

In the paper

“Additionally, A-1331852 and A-1155463, which are thought to inhibit BCL-XL, have also been shown to exhibit senolytic activity202.”

What the sources say

• Supported

  The Results report that A1331852 and A1155463, identified as BCL-XL inhibitors, selectively reduced the viability and survival of senescent HUVECs and IMR90 cells and induced apoptosis. The Discussion explicitly calls both compounds senolytic in those cell types, though not in primary human preadipocytes. (LLM, conf=0.94)

  cites [202] Zhu, Y. et al. New agents that target senescent cells: the flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463. Aging 9, 955–963 (2017). source

In the paper

“Importantly, the administration of dasatinib and quercetin has shown effectiveness in reducing the expression of p16 and SA-β-gal in a phase I clinical trial among patients with diabetic kidney disease211 and idiopathic pulmonary disease212.”

What the sources say

• Supported

  The Methods describe a Phase 1 pilot study of dasatinib plus quercetin in people with diabetic kidney disease. The Results report significant reductions in adipose-tissue p16INK4A-positive and SAβgal-positive cells. In the citing sentence, this source is attached to the diabetic kidney disease group; the idiopathic pulmonary disease group has a separate citation. (LLM, conf=0.93)

  cites [211] Hickson, L. J. et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. EBioMedicine 47, 446–456 (2019). source
• Partly supported

  The Abstract (Interpretation; page unavailable) confirms that this was a first-in-human trial of dasatinib plus quercetin in patients with idiopathic pulmonary fibrosis. But the Discussion (Limitations; page unavailable) says the trial could not test senescent-cell clearance in patients’ lungs and that changes in circulating markers were inconclusive. The reported reduction in lung p16 expression was in mice, not trial participants; the paper does not establish a reduction in SA-β-gal in these patients. The diabetic kidney disease portion is attached to citation 211, not this source. (LLM, conf=0.90)

  cites [212] 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

“Nanoparticles containing either fluorophores or cytotoxic agents coated with galacto-oligosaccharides were found to preferentially deliver cytotoxic cargo to senescent cells because of the higher level of SA-β-gal activity in these cells218.”

What the sources say

• Supported

  The Results (Figure 1 caption; page not provided) describe galacto-oligosaccharide-coated nanoparticles whose cargo is preferentially released in senescent cells by lysosomal β-galactosidase. The Results section on therapeutic activity reports preferential release of doxorubicin in senescent cells, supporting the cytotoxic-cargo part of the claim. (LLM, conf=0.92)

  cites [218] Munoz-Espin, D. et al. A versatile drug delivery system targeting senescent cells. EMBO Mol. Med. https://doi.org/10.15252/emmm.201809355 (2018). source

In the paper

“Adipose tissue, skeletal muscle and the eyes of BubR1 hypomorphic mice express high levels of p16 and other senescence-associated features192.”

What the sources say

• Supported

  The Yin section says eye, adipose tissue and skeletal muscle show p16Ink4a induction in response to BubR1 insufficiency. The Yang section reports high p19Arf in all three tissues, while “Linking cellular senescence in vivo to aging” reports accumulation of senescent cells in skeletal muscle and fat. Page numbers are not provided in our copy. (LLM, conf=0.90)

  cites [192] Baker, D. J., Jin, F. & van Deursen, J. M. The yin and yang of the Cdkn2a locus in senescence and aging. Cell Cycle 7, 2795–2802 (2008). source

In the paper

“Other senolytics, including HSP90 inhibitors213,214 and piperlongumine215,216, have also been demonstrated to be selective towards senescent cells.”

What the sources say

• Supported

  The cited paper is attached to the HSP90-inhibitor portion of the sentence, not the separately cited piperlongumine portion. In “Senotherapeutics: senolytic and senomorphic drugs” (page unavailable), it defines senolytics as agents that specifically kill senescent cells and reports that HSP90 inhibitors induce apoptosis in senescent murine and human cells. (LLM, conf=0.90)

  cites [213] Fuhrmann-Stroissnigg, H., Niedernhofer, L. J. & Robbins, P. D. Hsp90 inhibitors as senolytic drugs to extend healthy aging. Cell Cycle 17, 1048–1055 (2018). source
• Supported

  The Introduction identifies HSP90 inhibitors as agents that specifically induce apoptosis in senescent cells. The Results section reports that they selectively kill senescent cells and shows senolytic activity across several cell types. This source is cited for the HSP90-inhibitor portion of the sentence, not the separately cited piperlongumine portion. (LLM, conf=0.94)

  cites [214] Fuhrmann-Stroissnigg, H. et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat. Commun. 8, 422 (2017). source
• Supported

  The Abstract reports that piperlongumine preferentially killed senescent human WI-38 fibroblasts across three methods of inducing senescence. This supports the piperlongumine portion of the citing sentence; the HSP90-inhibitor portion is attributed to other citations. (LLM, conf=0.92)

  cites [215] Wang, Y. et al. Discovery of piperlongumine as a potential novel lead for the development of senolytic agents. Aging 8, 2915–2926 (2016). source
• Supported

  The Introduction states that piperlongumine preferentially kills senescent WI-38 cells over normal WI-38 cells. This supports the piperlongumine portion of the citing sentence; the HSP90-inhibitor portion is attached to other citations, not this paper. (LLM, conf=0.93)

  cites [216] Liu, X. et al. Senolytic activity of piperlongumine analogues: synthesis and biological evaluation. Bioorg. Med. Chem. 26, 3925–3938 (2018). source

In the paper

“The use of various natural flavonoids, including quercetin and fisetin, either alone or in combination with dasatinib, a pan-tyrosine kinase inhibitor, can stimulate senolysis in a variety of contexts in vitro and in vivo199,207–210.”

What the sources say

• Partly supported

  The Results sections on DQ treatment report that dasatinib plus quercetin killed senescent fibroblasts in vitro and reduced senescence markers in bleomycin-injured mice in vivo. Our copy does not report senolysis by fisetin or by either flavonoid used alone, so it supports only the combination portion of the claim. (LLM, conf=0.88)

  cites [199] Schafer, M. J. et al. Cellular senescence mediates fibrotic pulmonary disease. Nat. Commun. 8, 14532 (2017). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section on JAK inhibition reports changes in chemokine secretion and monocyte attraction by human preadipocytes, not senolysis. Searches for quercetin, fisetin, dasatinib, and senolytic effects found no passage addressing flavonoid-induced senolysis in vitro or in vivo; page numbers were unavailable in our copy. (LLM, conf=0.78)

  cites [207] Zhu, Y. et al. Inflammation and the depot-specific secretome of human preadipocytes. Obesity 23, 989–999 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  The age-related and hypercholesterolemia-induced vascular pathology sections report that dasatinib plus quercetin reduced senescent-cell markers in two mouse settings. This paper does not establish senolysis by fisetin, by either flavonoid alone, or in vitro, so it supports only part of the sentence attributed to it. (LLM, conf=0.87)

  cites [208] Roos, C. M. et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15, 973–977 (2016). sourceExperimental — accuracy not yet measured
• Supported

  The Results report that fisetin reduced senescence in cultured mouse and human cells, while the Introduction describes reduced senescence markers in mice. The Introduction and Discussion also report senolytic effects of quercetin combined with dasatinib in cell culture and mice. Page numbers were not available in our copy. (LLM, conf=0.90)

  cites [209] Yousefzadeh, M. J. et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36, 18–28 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results sections on candidate senolytic drugs in vitro and on dasatinib and quercetin in vivo report selective killing by quercetin alone or with dasatinib in several cell types, and reduced senescent-cell markers after the combination was given to mice. The passages do not report senolytic effects of fisetin, so this source does not support that part of the sentence. (LLM, conf=0.88)

  cites [210] 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

“Promoting proteasomal degradation of BCL-2 through EF24 treatment also results in the selective killing of senescent cells205.”

What the sources say

• Partly supported

  The Results sections report that EF24 selectively induces apoptosis in senescent cells and that proteasome inhibition blocks its reduction of Bcl-2-family proteins. But the reduction in Bcl-2 itself was not statistically significant; the significant reductions were in Bcl-xl and Mcl-1. The paper also presents proteasomal degradation as a suggested mechanism, not an established cause of the selective killing. (LLM, conf=0.90)

  cites [205] Li, W., He, Y., Zhang, R., Zheng, G. & Zhou, D. The curcumin analog EF24 is a novel senolytic agent. Aging 11, 771–782 (2019). sourceExperimental — accuracy not yet measured

In the paper

“The rapidly ageing BubR1 hypomorphic mouse model has been valuable to demonstrate that cellular senescent cells cause ageing and disease191,192.”

What the sources say

• ?Not checked — no full text of the sourcecites [191] Baker, D. J. et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat. Genet. 36, 744–749 (2004). source
• Partly supported

  The Introduction (page unavailable) identifies BubR1 hypomorphic mice as a rapidly aging model suited to investigating whether cellular senescence contributes to aging. “Linking cellular senescence in vivo to aging” reports that senescent cells accumulate in affected muscle and fat and links senescence to aging in those tissues. It does not establish the broader claim that senescent cells cause aging and disease generally; the Introduction says their direct contribution to organismal aging remains a matter of debate. (LLM, conf=0.86)

  cites [192] Baker, D. J., Jin, F. & van Deursen, J. M. The yin and yang of the Cdkn2a locus in senescence and aging. Cell Cycle 7, 2795–2802 (2008). sourceExperimental — accuracy not yet measured

In the paper

“In vitro, the SASP factors IL-8, GROα, IL-6, and IGFBP7 reinforce the senescent phenotype in an autocrine manner74,93,185.”

What the sources say

• Partly supported

  The Discussion (page not available) says IL-6 acts in an autocrine, cell-autonomous fashion to implement oncogene-induced senescence, and identifies IL-8 as another cytokine involved in that response. Our copy does not establish autocrine reinforcement by IL-8, GROα, or IGFBP7; searches for GROα and IGFBP7 found no supporting passage. (LLM, conf=0.87)

  cites [74] Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results report that knocking down or neutralizing IL-8 and GROα alleviated oncogene-induced senescence in cultured cells, supporting a reinforcing role for those factors. The Discussion says autocrine CXCR2 activation is possible, not established. This paper does not show that IL-6 reinforces senescence, and it discusses IGFBP7's senescence-related action as paracrine rather than autocrine. (LLM, conf=0.90)

  cites [93] Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [185] Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M. & Green, M. R. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132, 363–374 (2008). source

In the paper

“treatment of BubR1 hypomorphic mice harbouring the INK-ATTAC transgene to remove p16-expressing cells beginning at weaning age attenuated the accumulation of senescent cells and premature ageing in skeletal muscle, eye and adipose tissue11”

What the sources say

• Supported

  In the main text describing Figs. 2–3 (page not supplied), the authors report treating BubR1 hypomorphic INK-ATTAC mice from three weeks of age, delaying muscle decline and cataracts and preventing adipose-tissue loss. They also report reduced senescence indicators in adipose tissue, skeletal muscle and eye compared with untreated mice. (LLM, conf=0.94)

  cites [11] Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011). This study demonstrates that selective elimination of p16-expressing senescent cells is safe and capable of modulating age-related dysfunction in a premature aged mouse model. source

In the paper

“The literature is becoming inundated with evidence that senescent cells accumulate in a variety of age-associated diseases13.”

What the sources say

• Supported

  The ‘Senescence and age-related diseases’ section names numerous age-related diseases associated with cellular senescence and states that senescent cells accumulate at sites of disease. That directly supports the attributed claim about accumulation in a variety of age-associated diseases. (LLM, conf=0.94)

  cites [13] Childs, B. G. et al. Senescent cells: an emerging target for diseases of ageing. Nat. Rev. Drug Discov. 16, 718–735 (2017). source

In the paper

“Senescent cells frequently upregulate negative modulators of apoptosis, including members of the BCL-2 family (including BCL-2, BCL-W and BCL-XL), which confers resistance to apoptosis-inducing signals14,15.”

What the sources say

• Supported

  The Results section reports increased BCL-2, BCL-W and BCL-XL in the tested senescent cells. The Discussion identifies BCL-family protein activation as a mechanism of their increased resistance to apoptosis, particularly implicating BCL-W and BCL-XL. (LLM, conf=0.91)

  cites [14] Yosef, R. et al. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat. Commun. 7, 11190 (2016). source
• Partly supported

  The paper’s results passage (indexed under Abstract; page unavailable) reports increased anti-apoptotic BCL-xL in senescent cells and suggests that BCL-2 and BCL-xL protect them from apoptotic death. It does not report increased BCL-2—indeed, it says the observed sensitivity did not correlate with increased BCL-2—or establish increased BCL-W. (LLM, conf=0.88)

  cites [15] 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

In the paper

“Idiopathic pulmonary fibrosis is associated with telomere shortening and markers of cellular senescence in humans264.”

What the sources say

• Supported

  The Results (page unavailable) report shorter telomeres in human lung fibroblasts from IPF patients than in age-matched controls. The Results also report increased senescence markers, including β-galactosidase activity and p21 and p16 protein expression, in those fibroblasts. (LLM, conf=0.94)

  cites [264] Alvarez, D. et al. IPF lung fibroblasts have a senescent phenotype. Am. J. Physiol. Lung Cell Mol. Physiol. 313, L1164–L1173 (2017). source

In the paper

“Exciting recent work has demonstrated that senolytic CAR T cell therapy can attenuate senescence-associated diseases226.”

What the sources say

• Supported

  The paper reports that uPAR-directed CAR T cells restored tissue homeostasis in mouse models of liver fibrosis and extended survival in mice with treated lung adenocarcinoma. It presents these results as evidence of therapeutic potential for senescence-associated diseases; the demonstrated benefits are preclinical. (LLM, conf=0.92)

  cites [226] Amor, C. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127–132 (2020). This study demonstrates the feasibility of targeting senescent cells in a variety of conditions by chimeric antigen receptor T cell-mediated therapy. source

In the paper

“Additionally, recent studies have further shown the potential of delivering cytotoxic factors to lysosomes of senescent cells by galactose-modifying prodrugs or cytotoxic agents219,220.”

What the sources say

• Partly supported

  The Discussion (page unavailable) reports that galactose-modified duocarmycin prodrugs are converted to cytotoxic drugs through processing by lysosomal β-galactosidase and selectively affect senescent cells. The Results (page unavailable) show that reducing this enzyme abolishes the prodrug’s selective killing. The paper does not establish that galactose modification specifically delivers the agents to lysosomes; it demonstrates dependence on a lysosomal enzyme. (LLM, conf=0.82)

  cites [219] Guerrero, A. et al. Galactose-modified duocarmycin prodrugs as senolytics. Aging Cell 19, e13133 (2020). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction (page not provided) says galacto-oligosaccharide-coated nanoparticles preferentially deliver cytotoxic drugs to senescent-cell lysosomes, where the cargo is released. It also describes this paper’s galactose-modified Navitoclax prodrug, whose senolytic activity depends on senescent-cell β-galactosidase. (LLM, conf=0.92)

  cites [220] González-Gualda, E. et al. Galacto-conjugation of navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity. Aging Cell 19, e13142 (2020). source

In the paper

“The cytokines IL-21 and IL-15 have been suggested to substantially boost NK cell-mediated immunity against cancer cells222–225.”

What the sources say

• Partly supported

  The Discussion (page unavailable) reports that IL-21 enhanced NK-cell elimination of cetuximab-coated tumor cells, supporting the IL-21 part of the claim. The Introduction notes that NK cells have IL-15 receptors, and the Discussion mentions a mouse study comparing IL-15 with IL-21, but neither passage establishes that IL-15 substantially boosts NK-cell-mediated immunity against cancer cells. (LLM, conf=0.85)

  cites [222] McMichael, E. L. et al. IL-21 enhances natural killer cell response to cetuximab-coated pancreatic tumor cells. Clin. Cancer Res. 23, 489–502 (2017). sourceExperimental — accuracy not yet measured
• Supported

  The Cytotoxicity assays section identifies the NK-cell targets as tumor cell lines. The Results section on NKG2D reports that IL-15/IL-21 strongly promoted killing of one of those lines, supporting the hedged claim that the cytokines can boost NK-cell activity against cancer cells in this experimental setting. (LLM, conf=0.92)

  cites [223] Brady, J. et al. The interactions of multiple cytokines control NK cell maturation. J. Immunol. 185, 6679–6688 (2010). source
• Partly supported

  The Abstract (page not provided) says IL-15/IL-15Rα complexes were proposed as a potent tumor immunotherapy and that transient stimulation boosted NK-cell function. The Results and Discussion (page not provided) also calls the complexes promising against cancer, while warning that sustained stimulation impairs NK-cell function. Our copy does not support the claim about IL-21. (LLM, conf=0.87)

  cites [224] Elpek, K. G., Rubinstein, M. P., Bellemare-Pelletier, A., Goldrath, A. W. & Turley, S. J. Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc. Natl Acad. Sci. USA 107, 21647–21652 (2010). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [225] Rautela, J. & Huntington, N. D. IL-15 signaling in NK cell cancer immunotherapy. Curr. Opin. Immunol. 44, 1–6 (2017). source

In the paper

“Stimulation of innate immune response with poly(I:C), a simulator of viral infection, improves senescent cell clearance145.”

What the sources say

• Partly supported

  The Results section, “Senescent stellate cells are selectively targeted by NK cells” (page unavailable), says polyI:C was used to enhance the immune response and that treated mouse livers contained fewer senescent cells than controls. Our copy does not describe polyI:C as simulating viral infection, so that characterization is not supported by this source. (LLM, conf=0.84)

  cites [145] Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008). This study demonstrates that immune cell targeting of senescent cells limits dysfunction in the liver. sourceExperimental — accuracy not yet measured

In the paper

“Recently, sequence-specific inhibition of DDR activation by antisense oligonucleotides (ASOs)250 and their use in cultured cells and in mouse models to specifically inhibit telomeric DDR38 provided support for this approach.”

What the sources say

• Supported

  The Results section on sequence-specific inhibition reports that antisense oligonucleotides reduced DDR signaling at targeted breaks in cultured cells while leaving other damaged sites unaffected. The mouse-model and telomeric-DDR clause is attached to citation 38, not to this source's citation 250. (LLM, conf=0.93)

  cites [250] Michelini, F. et al. Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nat. Cell Biol. 19, 1400–1411 (2017). sourceExperimental — accuracy not yet measured
• Supported

  The Results sections “Antisense oligonucleotides allow DDR inhibition at telomeres” and “Telomeric DDR inhibition in vivo” report that sequence-specific ASOs reduced telomeric DDR markers in cultured mouse cells and in a mouse model. The paper also reports that the ASOs did not affect the response to ionizing-radiation-induced damage, supporting the claim of telomere-specific inhibition. (LLM, conf=0.94)

  cites [38] Rossiello, F. et al. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs. Nat. Commun. 8, 13980 (2017). sourceExperimental — accuracy not yet measured

In the paper

“Importantly, concerns regarding the safety of telomerase forced expression in damaged tissues, in particular by fuelling cancer progression, have been mitigated by the recent demonstration that oncogene-expressing mice do not show accelerated tumorigenesis on such treatment266.”

What the sources say

• Supported

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

  cites [266] Munoz-Lorente, M. A. et al. AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer. PLoS Genet. 14, e1007562 (2018). source

In the paper