Guidelines for minimal information on cellular senescence experimentation in vivo

In the paper

“The establishment of the so-called “minimum information for experimentation” (for example, “Minimum information about a microarray experiment” (MIAME) or “Minimal information for studies of extracellular vesicles” (MISEV)) led to an improvement in data reporting quality, harmonization, and reproducibility2,3.”

What the sources say

• Partly supported

  The Introduction identifies MISEV as minimum-information guidelines intended to improve EV reporting, reliability, and reproducibility. But it says the MISEV2014 authors *hoped* to improve reliability and reproducibility; it does not establish that the guidelines led to the claimed improvements in reporting quality, harmonization, and reproducibility. This source concerns MISEV, while the sentence also cites another source for MIAME. (LLM, conf=0.85)

  cites [2] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [3] source

In the paper

“This leads to persistent activation of the DNA damage response (DDR), which contributes to stable cell-cycle arrest and transcriptional induction of pro-inflammatory SASP factors16–18.”

What the sources say

• Partly supported

  The Introduction (page not provided) describes senescence as irreversible cell-cycle arrest and says senescent cells secrete inflammatory SASP factors. The Results section on ALISE and the SASP (page not provided) reports DNA-damage foci and SASP components, but does not establish that persistent DDR activation causes both arrest and transcriptional induction of those factors; SASP components declined after lipid deprivation even though DNA-damage foci did not. (LLM, conf=0.84)

  cites [16] sourceExperimental — accuracy not yet measured
• Supported

  The Introduction (page not supplied) states that persistent DDR causes irreversible proliferation arrest in proliferation-competent cells and that senescent cells undergo gene-expression shifts toward a pro-inflammatory secretion pattern. These statements support the attributed link between DDR, stable cell-cycle arrest, and pro-inflammatory SASP factors. (LLM, conf=0.90)

  cites [17] source
• ?Not checked — no full text of the sourcecites [18] source

In the paper

“In addition, in vivo, a number of cells, such as macrophages, might have an inherently high β-galactosidase activity due to the high mass and/or number of lysosomes44.”

What the sources say

• ?Could not verify

  The Materials and Methods sections on the SA-β-Gal assay and whole-mount SA-β-Gal staining describe staining procedures, but do not discuss inherently high β-galactosidase activity in macrophages or attribute it to lysosomal mass or number. Searches for macrophages and lysosomes found no passage addressing that explanation; page numbers were unavailable in our copy. (LLM, conf=0.76)

  cites [44] sourceExperimental — accuracy not yet measured

In the paper

“Nonetheless, several recent publications have successfully used anti-murine p16Ink4a antibodies in various applications6–8.”

What the sources say

• ?Could not verify

  The Key Resources Table (Additional information; page not provided) lists a p21 antibody but no anti-murine p16Ink4a antibody. Searches for p16Ink4a, Cdkn2a, and anti-murine p16 antibodies found no passage describing their use, so our copy cannot verify the attributed claim. (LLM, conf=0.78)

  cites [6] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [7] source
• Supported

  The Materials and Methods (Immunoblotting; page not available) states that the authors probed cell lysates with an anti-p16 antibody and developed the resulting blots. The Mice section identifies the study animals as mice. This supports the paper’s use as one example of an anti-murine p16 antibody application. (LLM, conf=0.87)

  cites [8] source

In the paper

“One of the most recognizable and common markers of cellular senescence is senescence-associated beta-galactosidase (SA-β-gal)37, which reflects the activity of a lysosomal enzyme that cleaves terminal β-d-galactose residues from β-D-galactosides38.”

What the sources say

• ?Could not verify

  The Results section reports high SA-β-gal activity as evidence of senescence, but does not explain the enzyme’s location or what it cleaves. Searches for lysosomal β-galactosidase and terminal galactose cleavage found no passage addressing the biochemical claim attached to this citation; page numbers were not available in our copy. (LLM, conf=0.75)

  cites [37] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results passages concern transcription and DNA-damage responses, not SA-β-gal or its enzymatic activity. Searches for SA-β-gal, lysosomal enzyme, galactose, and galactosides found no passage in our copy addressing the claimed cleavage reaction; the References section does not establish it. (LLM, conf=0.76)

  cites [38] sourceExperimental — accuracy not yet measured

In the paper

“Telomeric DNA damage and attrition leads to DDR foci colocalizing with telomeric sequences known as telomere-associated foci (TAF) or telomere-induced foci (TIF)19,20.”

What the sources say

• ?Could not verify

  The available text (labelled Abstract; no page given) reports DNA-damage-response foci in senescent and bystander fibroblasts, but does not connect them to telomeric DNA damage or attrition. Searches for telomeres, TAF, and TIF found no passage identifying foci that colocalize with telomeric sequences. (LLM, conf=0.75)

  cites [19] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Abstract says that human plaques contain cells with shortened telomeres, but it does not describe DNA damage response foci colocalizing with telomeric sequences. Searches for telomere-associated foci, telomere-induced foci, and telomeric DNA damage found no passage in our copy addressing that claim. (LLM, conf=0.73)

  cites [20] sourceExperimental — accuracy not yet measured

In the paper

“The induction of cellular senescence has been shown to cause a reduction in certain components of the nuclear envelope, especially the structural protein Lamin B111 (LMNB1; Fig. 1 C).”

What the sources say

• Partly supported

  The Results report more LMNB1-negative hippocampal neurons with age, and the Discussion identifies reduced LMNB1 as a marker of senescence. The paper does not show that inducing senescence causes the reduction or report reductions in other nuclear-envelope components. The indexed passages provide section labels but no page numbers. (LLM, conf=0.84)

  cites [11] sourceExperimental — accuracy not yet measured

In the paper

“Organelle dysregulation occurring in senescent cells, especially senescence-associated mitochondrial dysfunction (SAMD)32, leads to increased generation of reactive oxygen species (ROS), causing oxidative damage.”

What the sources say

• ?Could not verify

  The Discussion mentions reactive oxygen species in ATM-deficient cells as a possible explanation for HMGB1 release, not as a consequence of senescence-associated mitochondrial dysfunction. Searches for mitochondrial dysfunction and oxidative damage found no passage in our copy linking them to increased ROS generation in senescent cells. (LLM, conf=0.75)

  cites [32] sourceExperimental — accuracy not yet measured

In the paper

“Both proliferation-competent glial cells (which constitute approximately 50% of brain cells) and postmitotic neurons can be positive for markers of cellular senescence in aging, obesity, traumatic injury, and neurodegeneration31,45–49, among other conditions.”

What the sources say

• ?Not checked — no full text of the sourcecites [31] source
• Partly supported

  The Introduction ('What is cell senescence?'; page unavailable) says senescence-related markers occur in aged postmitotic cells and describes a senescence-like response in both proliferation-competent and postmitotic cells during aging. The References identify neurons as an example of postmitotic cells, but the paper does not establish the claim specifically for glial cells or for obesity, traumatic injury, and neurodegeneration. (LLM, conf=0.85)

  cites [45] sourceExperimental — accuracy not yet measured
• Partly supported

  The Conclusions (page not available) say post-mitotic cells can acquire senescence-like features, and the paper links senescence to neurodegenerative disorders and discusses senescent cells in the brains of obese and aging mice. Our copy does not establish the claim specifically for proliferation-competent glial cells and postmitotic neurons across all four listed conditions, particularly traumatic injury. (LLM, conf=0.82)

  cites [46] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [47] source
• ?Could not verify

  The paper’s sections on senescence model systems and live-cell delivery describe cell lines, airway organoids, tumors, and lung tissue, not senescence markers in glial cells or neurons. Searches for glia, neurons, brain, obesity, traumatic injury, and neurodegeneration found no passage addressing the attributed claim; an Alzheimer’s-related title appears only in the References (page unavailable). (LLM, conf=0.76)

  cites [48] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [49] source

In the paper

“In the context of KRAS-induced lung tumorigenesis, both resident67 and monocyte-derived68 macrophages exhibit senescence-related alterations.”

What the sources say

• ?Could not verify

  Citation 68 is attached to the claim about monocyte-derived macrophages. The paper’s Abstract and Discussion describe JunB-driven senescence in dermal fibroblasts and skin aging; searches for KRAS-induced lung tumorigenesis and monocyte-derived macrophages found no passage addressing the cited claim. No page numbers were supplied for these passages. (LLM, conf=0.76)

  cites [67] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section on aging and fibroblast priming concerns human skin fibroblasts, while the Methods section mentions macrophages only as a cell type identified by marker genes. Searches for KRAS-induced lung tumorigenesis and macrophage senescence found no passage addressing alterations in resident macrophages, the part of the sentence marked with citation 67. (LLM, conf=0.78)

  cites [68] sourceExperimental — accuracy not yet measured

In the paper

“In various murine liver injury models, stellate cells can acquire senescence markers, including p21, p16, and SA-β-gal, and express certain SASP factors80–83.”

What the sources say

• ?Could not verify

  The Results section on senescence reports p16-positive cells in aging mouse lungs, predominantly alveolar macrophages, not stellate cells in liver injury models. Searches for hepatic stellate cells, liver injury, p21, and SA-β-gal found no passage addressing the attributed claim; the Discussion’s general account of senescent-cell secretions does not establish SASP expression by hepatic stellate cells. Page numbers were not available in our copy. (LLM, conf=0.76)

  cites [80] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Discussion mentions senescence markers in hepatocytes, while the Results report p21, p16 and SASP factors in aging bone cells. Neither section addresses stellate cells in murine liver injury models; searches for stellate cells and liver injury found no passage supporting that specific claim. No page numbers were available in our copy. (LLM, conf=0.76)

  cites [81] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section, “Induction of senescence is sufficient to increase RANKL production” (page unavailable), reports p21, β-galactosidase activity, p16, and a SASP component in bone marrow stromal cells or osteocyte-enriched bone. A search for hepatic stellate cells and murine liver injury models found no passage addressing those cells or models, so the cited paper does not verify the claim as stated. (LLM, conf=0.76)

  cites [82] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction discusses p16, p21, and SASP as features of senescent cells, while the Results describe these markers in bone cells or cultured fibroblasts (page numbers unavailable). Searches for stellate cells and liver injury found no passage addressing whether stellate cells acquire these markers in murine liver injury models. (LLM, conf=0.75)

  cites [83] sourceExperimental — accuracy not yet measured

In the paper

“Numerous markers of senescence (including p21, p16Ink4a, γ-H2A.X, and TAF/TIF) have been identified in skin cell types, such as keratinocytes and fibroblasts (Fig. 2 B), in conditions such as injury, aging, and accelerated aging14,54–57.”

What the sources say

• Partly supported

  The Results sections on hepatocyte senescence identify p21, p16 and γH2A.X-associated TAF as senescence markers, including in aging hepatocytes. The Methods section on mouse adult fibroblasts describes fibroblasts obtained from ear clippings, but our copy does not establish the listed markers in skin keratinocytes or fibroblasts across injury, aging and accelerated-aging conditions. (LLM, conf=0.86)

  cites [14] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page unavailable) identify γH2AX as a senescence marker and measure it in senescent human BJ fibroblasts; the Discussion also names p16Ink4a as a marker associated with aging. The paper does not establish the full claimed set of markers in skin keratinocytes and fibroblasts across injury, aging, and accelerated aging: p21 appears in an immunoblotting method, while TAF/TIF, keratinocytes, and accelerated aging are not addressed. (LLM, conf=0.86)

  cites [54] sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction identifies p21, p16Ink4a and γ-H2AX as senescence markers, and the Results report p16Ink4a and p21 changes in human fibroblasts. The cited paper does not establish the full claim about markers in skin keratinocytes, TAF/TIF, or injury and accelerated-aging conditions. (LLM, conf=0.87)

  cites [55] sourceExperimental — accuracy not yet measured
• Partly supported

  The section “Senescent cells influencing macrophages and vice versa” reports a p16INK4a-dependent senescence program in resident fibroblasts during chronic venous leg ulcers, supporting the injury-related fibroblast example. Our copy does not establish the listed markers as a set in skin cells, identify keratinocytes, or describe those markers in skin during aging or accelerated aging. No page number is available in the indexed copy. (LLM, conf=0.84)

  cites [56] sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page not supplied) links p16 and p21 to cellular senescence, and the Discussion reports increased p16 in astrocytes after brain injury. The paper does not establish the listed markers in skin keratinocytes or fibroblasts across injury, aging, and accelerated aging, and the passages do not address γ-H2A.X or TAF/TIF. (LLM, conf=0.86)

  cites [57] sourceExperimental — accuracy not yet measured

In the paper

“numerous other senescence markers, such as p21, p16, SASP factors, and DNA damage, are found across populations of adipose tissue cells7,31,84–87 (Fig. 2 F).”

What the sources say

• ?Not checked — no full text of the sourcecites [7] source
• ?Not checked — no full text of the sourcecites [31] source
• Partly supported

  The Results sections on fracture sites and the fracture callus report p21 (Cdkn1a), p16 (Cdkn2a), SASP genes, and telomere-associated DNA damage in mouse bone or callus (page unavailable). They do not establish that these markers are found across populations of adipose tissue cells. (LLM, conf=0.88)

  cites [84] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section (page unavailable) identifies p21-positive, p16-positive, and dual-positive populations in irradiated bone, and reports SASP factors in bone. The paper also measures marrow adiposity, but it does not establish that these markers or DNA damage are found across populations of adipose tissue cells; that tissue-specific part of the claim is unsupported. (LLM, conf=0.84)

  cites [85] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [86] source
• Partly supported

  Extended Data Figure 10 reports a senescence marker (loss of Lamin B1) alongside the SASP factor IL-6 in mouse white adipose tissue. Extended Data Figure 1 assesses p21, p16, SASP genes, and DNA-damage foci in senescent cell cultures, not across adipose-tissue cell populations. The paper therefore supports the adipose-tissue SASP example, but not the full list or its distribution across adipose cell populations. (LLM, conf=0.87)

  cites [87] sourceExperimental — accuracy not yet measured

In the paper

“Keratinocytes and fibroblasts can be further divided into different subtypes.”

What the sources say

• ?Could not verify

  The Materials and Methods section mentions a keratinocyte chemoattractant measured in rat serum, not keratinocyte subtypes. Searches for keratinocytes, fibroblasts, and subtypes found no passage in our copy addressing whether either cell type can be divided into subtypes. The copy instead focuses on aged rats’ cognition and hippocampal changes. (LLM, conf=0.76)

  cites [58] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Methods section on single-cell preparation and Extended Data Figure 4 describe sorting brain cells, including astrocytes and microglia, rather than classifying skin cells. Searches for keratinocytes, fibroblasts, and skin-cell subpopulations found no passage in our copy addressing whether keratinocytes or fibroblasts have subtypes. (LLM, conf=0.75)

  cites [59] sourceExperimental — accuracy not yet measured

In the paper

“Keratinocytes display different properties across different strata of the epidermis”

What the sources say

• ?Could not verify

  The Results and Discussion passages describe differences between apical and basal dendrites in the rat hippocampus, not keratinocytes in epidermal strata. Searches for the claim’s wording and for keratinocytes, epidermal layers, and skin differentiation found no passage addressing the claim. No page numbers were available in our copy. (LLM, conf=0.77)

  cites [58] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Extended Data passages discuss astrocytes, microglia, and other brain cells, not keratinocytes. Searches for keratinocytes, epidermal strata, and skin layers found no passage in our copy addressing how keratinocyte properties vary across the epidermis. (LLM, conf=0.77)

  cites [59] sourceExperimental — accuracy not yet measured

In the paper

“while the presence of senescence markers has been proven even in post-mitotic cells”

What the sources say

• ?Not checked — no full text of the sourcecites [31] source
• Supported

  The Introduction (“What is cell senescence?”) states that markers of the senescent phenotype’s building blocks were found in aged postmitotic cells. This supports the claim that senescence markers have been demonstrated in post-mitotic cells, while describing the phenotype as senescence-like. (LLM, conf=0.93)

  cites [45] source
• Supported

  The Conclusions, Open Questions, and Perspectives section says that post-mitotic cells can assume senescence-like features. This supports the claim that senescence markers can be present in those cells, though the paper cautions that no single marker is specific to senescence. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [46] source
• ?Not checked — no full text of the sourcecites [47] source
• ?Could not verify

  The Discussion describes senescence markers and detection in cell cultures and murine models, but the passages found do not identify the cells as post-mitotic. Searches for post-mitotic cells and for nondividing cell types did not find a passage establishing the claimed point. (LLM, conf=0.70)

  cites [48] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [49] source

In the paper

“Traditionally, these models contain luminescent or fluorescent reporter systems yielding increased signal dependent upon the expression level of p21 or p168,83,104–107.”

What the sources say

• ?Could not verify

  The Results section on chronic LPS inhalation describes wild-type and p21-knockout mice and measures p21 and p16 expression by immunoblotting and mRNA analysis. The Methods describe chemiluminescent immunoblots and immunofluorescent staining, but no luminescent or fluorescent reporter model whose signal depends on p21 or p16 expression (searched: reporter, luciferase, fluorescent signal). No page numbers are available in our copy. (LLM, conf=0.76)

  cites [8] sourceExperimental — accuracy not yet measured
• Supported

  The Methods section (p16-LOX-ATTAC mouse model) describes an EGFP cassette driven by the p16Ink4a promoter. The Results section (Development and validation of a model for eliminating specific SnC types) reports p16Ink4a-promoter-driven EGFP expression in unrecombined cells, supporting this paper as an example of a p16-linked fluorescent reporter model. (LLM, conf=0.88)

  cites [83] source
• ?Not checked — no full text of the sourcecites [104] source
• ?Could not verify

  The Retroviral Infections passage (indexed as Abstract; page not supplied) describes an E1A/ras construct and puromycin selection, not a p21- or p16-dependent reporter. A search for luminescent, fluorescent, and luciferase reporters found no passage in our copy addressing the claimed model design. (LLM, conf=0.76)

  cites [105] sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract describes in vivo bioluminescence imaging with a p16INK4a-luciferase transgenic reporter, supporting the luminescent p16 example. It does not describe fluorescent reporters, p21-based reporters, or establish that such systems are traditionally used across these models. (LLM, conf=0.85)

  cites [106] sourceExperimental — accuracy not yet measured
• Supported

  The Results section (“Detection of senescence in vivo”) describes a mouse model with a luciferase reporter at the p16 locus, used to measure p16 transcription. It reports that the luminescence signal increases with age, supporting this source as an example of the reporter models described. (LLM, conf=0.92)

  cites [107] source

In the paper

“It is important to note that activated macrophages, including tissue-infiltrating macrophages, express higher levels of p16 and stain positive for SA-β-gal even though they may not be senescent44.”

What the sources say

• ?Could not verify

  The Materials and Methods sections on SA-β-Gal staining describe how the assay was performed, not whether activated or tissue-infiltrating macrophages stain positive. Searches for macrophages alongside p16, SA-β-gal, and senescence found no passage in our copy addressing the claimed marker expression or whether those macrophages are senescent. (LLM, conf=0.76)

  cites [44] sourceExperimental — accuracy not yet measured

In the paper

“These models were primarily used to show how the absence of a single regulator of the senescence program affects physiology and pathology.”

What the sources say

• ?Could not verify

  The Introduction’s Cellular Senescence section describes models that transplant or selectively eliminate senescent cells. The Cellular Senescence in Immune Cells section describes deletion of Ercc1, a DNA-repair factor, and its effects on aging. Neither passage says that the models were primarily used to test how absence of a single regulator of the senescence program affects physiology and pathology; searches for that description and for senescence-regulator knockout models found no such passage. No page numbers were available in our copy. (LLM, conf=0.72)

  cites [97] sourceExperimental — accuracy not yet measured
• Partly supported

  The ‘Cellular senescence and immune cell fate decision’ section (page unavailable) says knockout mouse models of the CDKN2A locus revealed links between senescence and terminal differentiation. The hematopoietic progenitors/stem cells subsection also reports that deleting senescence-associated regulators affects stem-cell replication and leukemia prevalence. These examples support using such models to study physiological and pathological effects, but the paper does not say they were primarily used for that purpose, and its cited deletion example involves two regulators rather than a single one. (LLM, conf=0.82)

  cites [98] sourceExperimental — accuracy not yet measured

In the paper

“CDKN2A mRNA levels are regulated by transcription and mRNA stability104,111.”

What the sources say

• ?Not checked — no full text of the sourcecites [104] source
• Partly supported

  The Results section links p16Ink4a expression to changes at its gene promoter and reports RT-qPCR measurement of its expression, supporting transcriptional regulation. Neither those passages nor the searched passages address whether mRNA stability regulates CDKN2A mRNA levels. Page numbers are not available in our copy. (LLM, conf=0.86)

  cites [111] sourceExperimental — accuracy not yet measured

In the paper

“Cellular senescence is not a mammalian-specific phenomenon but is widespread across the animal kingdom, including vertebrate and invertebrate organisms.”

What the sources say

• Partly supported

  The Dear Editor section describes cellular senescence in mice and humans, supporting its occurrence in vertebrates. It does not address invertebrates or establish that senescence is widespread across the animal kingdom, so those parts of the claim are unsupported. (LLM, conf=0.84)

  cites [114] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [115] source
• ?Could not verify

  The Abstract and Discussion describe p16INK4a-expressing cells and senescent characteristics in mice, but do not address whether cellular senescence occurs across the animal kingdom. Searches for vertebrates, invertebrates, and evolutionary conservation found no passage supporting that claim; page numbers are unavailable in our copy. (LLM, conf=0.76)

  cites [116] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The paper’s introductory passage describes cellular senescence, and its study reports findings in mice, but neither addresses whether senescence occurs in invertebrates or is widespread across the animal kingdom. Searches for vertebrates, invertebrates, and non-mammalian organisms found no passage establishing that distribution. (LLM, conf=0.75)

  cites [117] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction describes replicative senescence in human diploid fibroblasts, and the Results and Discussion examine human WI-38 cells. Searches for vertebrate and invertebrate organisms and for senescence across nonmammalian species found no passage addressing whether senescence is widespread across the animal kingdom. (LLM, conf=0.76)

  cites [118] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [119] source
• ?Could not verify

  The paper’s Intracellular Molecules section discusses genetically modified rats, and its Conclusion and Perspectives compares rat and mouse models; neither addresses the distribution of cellular senescence across animals. Searches for “cellular senescence,” “invertebrate,” and related terms found no passage supporting the claim. Page numbers were not available in our copy. (LLM, conf=0.75)

  cites [120] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [121] source

In the paper

“A distinct subset of FAPs is the predominant source of CDKN2A mRNA in aged muscle.”

What the sources say

• ?Could not verify

  The Results passage on eliminating senescent cells discusses p16INK4a expression in senescent liver cells after partial hepatectomy, not CDKN2A mRNA in aged muscle. Searches for FAPs, fibro-adipogenic progenitors, and aged skeletal muscle found no passage identifying the predominant source of CDKN2A mRNA. (LLM, conf=0.76)

  cites [88] sourceExperimental — accuracy not yet measured

In the paper

“In addition, many immune cell types and subtypes develop a senescence-like state with increased expression of p16, p21, and SASP factors92,93.”

What the sources say

• ?Not checked — no full text of the sourcecites [92] source
• Partly supported

  The paper’s main text links senescence with p16 expression, and its concluding discussion describes the senescence-associated secretory phenotype (SASP). Its bone-marrow experiments do not identify multiple immune-cell types or subtypes, and the copy does not establish increased p21 expression in them. Page numbers are not supplied in the indexed copy. (LLM, conf=0.83)

  cites [93] sourceExperimental — accuracy not yet measured

In the paper

“Elimination of p16+ cells in the adipose tissue of transgenic mice reduces overall tissue senescence86,87”

What the sources say

• ?Not checked — no full text of the sourcecites [86] source
• ?Could not verify

  The section on L1 activation in human and mouse tissues reports that 3TC reduced inflammatory markers in aged mice but did not remove senescent cells. Extended Data Figure 10 examines adipose tissue after 3TC treatment. Neither passage addresses elimination of p16-positive adipose cells in transgenic mice or its effect on overall tissue senescence; searches for transgenic elimination and genetic ablation found no such result in our copy. (LLM, conf=0.75)

  cites [87] sourceExperimental — accuracy not yet measured

In the paper

“These and other models, for which it has been shown that accelerated aging depends, at least partly, on cellular senescence, are valuable for studying the impact of senescence on health and lifespan”

What the sources say

• ?Not checked — no full text of the sourcecites [86] source
• Supported

  The Cell non-autonomous mechanism section reports that transferring splenocytes from mutant mice shortened the lifespan of progeroid mice. It concludes that aged or senescent immune cells drive accelerated ageing and reduced lifespan in the mutant model, supporting the claim that cellular senescence contributes at least partly to accelerated ageing in these models (page unavailable in our copy). (LLM, conf=0.90)

  cites [99] source
• Partly supported

  The Abstract (page not provided) says immune senescence is only partially explained by organismal and cellular senescence. But the paper does not establish that accelerated aging in the models mentioned by the citing sentence depends on cellular senescence; its discussion of models concerns accelerated immune aging, not aging or lifespan generally. (LLM, conf=0.83)

  cites [100] sourceExperimental — accuracy not yet measured

In the paper

“Mouse models of rapid telomere shortening, dysfunctional mitosis or impaired DNA repair (Terc, BubR1, and Ercc1 mutant mice, respectively), display high levels of cellular senescence and accelerated aging86,99,100.”

What the sources say

• ?Not checked — no full text of the sourcecites [86] source
• Partly supported

  The Abstract (page not provided) says that reduced ERCC1–XPF impairs DNA repair, increases senescent cells in mouse tissues, and accelerates ageing. The paper’s passages do not address Terc or BubR1 mutant mice, so it supports only the Ercc1 portion of the claim. (LLM, conf=0.88)

  cites [99] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The “Immune Aging Concepts – From Mice to Men” section discusses telomere shortening and DNA repair in immune aging, but does not report outcomes for Terc, BubR1, or Ercc1 mutant mice. Searches for those mutants and for accelerated aging in the models found no passage establishing the claimed high cellular senescence or accelerated aging. (LLM, conf=0.76)

  cites [100] sourceExperimental — accuracy not yet measured

In the paper

“To address this limitation, transgenic mice with cell type-specific elimination of senescent cells were recently developed, p16-LOX-ATTAC mice75.”

What the sources say

• ?Could not verify

  The “Senolytic targeting of COVID-19 in vivo” section describes K18-hACE2-transgenic mice treated with senolytic drugs, not p16-LOX-ATTAC mice. Searches for “p16-LOX-ATTAC,” “ATTAC,” and cell type-specific genetic elimination found no passage in our copy addressing the claimed mouse model. (LLM, conf=0.75)

  cites [75] sourceExperimental — accuracy not yet measured

In the paper

“For example, the inclusion of selection cassettes, necessary in the process of generating recombinant mouse embryonic stem cells, can potentially interfere with the expression of the reporter transgene of interest, as observed for p16109,110, possibly because of unintended promoter activity.”

What the sources say

• ?Could not verify

  Section 3 describes p16 reporter mouse models and their transgenes, but does not address whether selection cassettes interfere with reporter expression. Searches for selection cassettes, recombinant embryonic stem cells, and promoter activity found no passage on that mechanism; page numbers were unavailable. (LLM, conf=0.73)

  cites [109] sourceExperimental — accuracy not yet measured
• ?Could not verify

  Materials and Methods (page unavailable) describes a p21 luciferase reporter generated by pronuclear microinjection, and the Discussion (page unavailable) describes how its signal tracks p21 expression. Neither addresses p16 or interference from selection cassettes; searches for those terms and embryonic stem cells found no relevant passage in our copy. (LLM, conf=0.74)

  cites [110] sourceExperimental — accuracy not yet measured

In the paper

“Models that enable the long-term tracking of senescent cell fate are also available108,109.”

What the sources say

• Partly supported

  The Results (Fig. 2; page unavailable) describe a p16Ink4a-luciferase mouse model whose signal was measured repeatedly over several weeks, supporting longitudinal monitoring of a senescence-associated signal. The paper says the reduced signal could reflect either clearance of senescent cells or reversal of senescence, so this model does not establish the fate of individual senescent cells. (LLM, conf=0.86)

  cites [108] sourceExperimental — accuracy not yet measured
• Partly supported

  Section 3 (page not provided) identifies two mouse models, p16-3MR and INK-ATTAC, whose transgenes permit visualization of p16INK4A-expressing cells. It does not say that these models enable long-term tracking of senescent cell fate. (LLM, conf=0.82)

  cites [109] sourceExperimental — accuracy not yet measured

In the paper

“Some of the most commonly used models are INK-ATTAC, p16–3MR, and p21-ATTAC55,77,86, but others have and are being generated (Table 2).”

What the sources say

• Partly supported

  The Introduction (page unavailable) identifies INK-ATTAC as a model used to eliminate p16-high cells. It does not identify p16-3MR or p21-ATTAC; it discusses a different p21-Cre model instead. Nor does it establish that the three named models are among the most commonly used. (LLM, conf=0.87)

  cites [55] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [77] source
• ?Not checked — no full text of the sourcecites [86] source

In the paper

“These changes limit the ability of the immune system to respond to pathogens or vaccinations94.”

What the sources say

• ?Could not verify

  The Results section on macrophage abundance describes immune-cell accumulation in adipose tissue and obesity-related inflammation, not the ability to respond to pathogens or vaccinations. Searches for immune responses to pathogens, infection, and vaccination found no passage addressing that claim; no page numbers are available in our copy. (LLM, conf=0.75)

  cites [94] sourceExperimental — accuracy not yet measured

In the paper

“Markers of senescence have been detected in birds (e.g., quail114), amphibians (e.g., axolotls115, xenopus116, and newts117), fish (e.g., zebrafish118 and killifish119), and invertebrates (e.g., hydra120 and Drosophila121).”

What the sources say

• ?Could not verify

  The Dear Editor section reports senescence markers in mouse embryos and mentions human embryonic development, but does not address birds, amphibians, fish, or invertebrates. Searches for the named animals and for non-mammalian senescence markers found no supporting passage in our copy. (LLM, conf=0.76)

  cites [114] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [115] source
• ?Could not verify

  The 'High-sensitivity fluorescent reporter of p16 INK4a in vivo' section (page unavailable) reports senescence markers in mouse lung fibroblasts, not in any of the animal groups named in the claim. Searches for the named species and for senescence markers in non-mammalian animals found no passage addressing those groups. (LLM, conf=0.76)

  cites [116] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The citation is attached to the quail example. The paper’s ‘Identification of p16 High senescent cells in vivo’ section reports senescence markers in mouse liver cells, but our copy does not address quail or other birds (searched: quail, birds, avian). (LLM, conf=0.76)

  cites [117] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results and Discussion describe senescence markers in human WI-38 fibroblasts, not in the animals named in the claim. Searches of our copy for the listed species and for senescence markers in nonhuman species found no passage addressing birds, amphibians, fish, or invertebrates. (LLM, conf=0.77)

  cites [118] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [119] source
• ?Could not verify

  The Introduction and Conclusion and Perspectives passages discuss genetically modified rat models, not markers of senescence in birds, amphibians, fish, or invertebrates. Searches for “senescence,” “hydra,” and the named animal groups found no passage in our copy addressing the attributed claim; the passages have no page numbers. (LLM, conf=0.77)

  cites [120] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [121] source

In the paper

“More recently, it has become clear that targeting senescent cells may be a promising strategy to reduce the growth and metastatic potential of tumors by altering the senescent tumor microenvironment147.”

What the sources say

• ?Could not verify

  The Results section, “Applying phenotypic profiling to senescence in vivo” (page not provided), reports that palbociclib treatment increased senescence markers in tumor xenografts and examines the cells’ morphology. It does not address whether targeting senescent cells reduces tumor growth or metastasis by altering the tumor microenvironment. Searches for those outcomes and for senolytic targeting found no supporting passage in our copy. (LLM, conf=0.75)

  cites [147] sourceExperimental — accuracy not yet measured

In the paper

“Senescence in non-mammals impacts on many aspects of organismal physiology, from development116,122 to regeneration (e.g., salamander limbs117, zebrafish fins118, whole hydra polyps120) and ageing119,123,124.”

What the sources say

• ?Could not verify

  Citation 117 is attached to the example of salamander limb regeneration. The paper’s Abstract and section on epithelial stem cell regeneration describe lung repair in mice, not salamanders or other non-mammals. Searches for salamanders, axolotls, limbs, zebrafish and hydra found no passage addressing that example. (LLM, conf=0.76)

  cites [116] sourceExperimental — accuracy not yet measured
• Supported

  The Introduction reports that cellular senescence recurs during salamander limb regeneration and is cleared by a macrophage-dependent mechanism. This supports the specific example—salamander limb regeneration—to which this citation is attached; the paper need not establish the sentence’s separately cited examples of development or ageing. (LLM, conf=0.90)

  cites [122] source
• Partly supported

  The paper’s opening summary (page unavailable) reports that age-induced senescence affects health in mice, supporting the ageing aspect of the citation. Mice are mammals, however, so it does not support the sentence’s claim specifically about non-mammals. (LLM, conf=0.88)

  cites [117] sourceExperimental — accuracy not yet measured

In the paper

“A senescence transcriptional signature could enable rapid detection of senescent cells, and multiple such gene sets have been described132–136,139.”

What the sources say

• ?Could not verify

  The Discussion addresses chicken senescence-related genes and proposes future work on their roles in senescence, but does not describe a senescence transcriptional gene set. Searches for senescence transcriptional signatures and gene-expression profiling found no passage supporting the claim. (LLM, conf=0.75)

  cites [132] sourceExperimental — accuracy not yet measured
• Supported

  The Transcriptomic profiling section describes several senescence-associated expression signatures, including lysosomal expansion, cell-cycle arrest, and inflammatory signatures. The Short article section (p. 2419) also identifies an rRNA-expression signature in senescent cells. Together, these support the claim that multiple senescence transcriptional gene sets have been described. (LLM, conf=0.90)

  cites [133] source
• Supported

  The Results section (page unavailable) says the authors used published senescence signatures for gene-set enrichment analysis and found them upregulated in the cells studied. The accompanying figure description identifies two published signatures, SASP and senescence-inflammatory response, supporting the claim that multiple such gene sets have been described. (LLM, conf=0.90)

  cites [134] source
• Supported

  The Discussion (page unavailable) describes transcriptomic analysis identifying a core group of senescence-associated genes as well as inducer-specific genes. This supports the cited point that more than one senescence transcriptional gene set has been described; the citation is attached to that point, not to the preceding proposal about rapid detection. (LLM, conf=0.86)

  cites [135] source
• Supported

  In “The Transcriptome of Secondary and a Subset of Primary Senescent Cells Is Characterized by Notch” (page unavailable), the paper describes distinct NIS, RIS, and secondary-senescence gene-expression signatures. This supports the attributed claim that multiple senescence transcriptional gene sets have been described; the citing sentence does not attribute rapid detection to this source specifically. (LLM, conf=0.92)

  cites [136] source
• ?Could not verify

  The 'Characterization of senescent cells' section lists individual biomarkers and predicts that multiple overlapping senescence signatures will ultimately be identified. It does not say that multiple transcriptional gene sets have already been described (searched: transcriptional signatures, gene sets, and transcriptomic profiles). The indexed passages provide no page numbers. (LLM, conf=0.72)

  cites [139] sourceExperimental — accuracy not yet measured

In the paper

“This has been successfully applied in fish118 and salamanders117,126, enabling both the functional assessment and validation of senescence through targeted reduction.”

What the sources say

• ?Could not verify

  The Introduction and Results and Discussion describe replicative senescence and p16 mRNA stability in human fibroblasts. Searches for senolytic treatment, fish, salamanders, and targeted removal of senescent cells found no passage addressing the attributed claim; page numbers were unavailable in our copy. (LLM, conf=0.78)

  cites [118] sourceExperimental — accuracy not yet measured
• Partly supported

  The section on dasatinib and quercetin reports targeted reduction of p16-high macrophages in mice, and the Discussion assesses consequences of removing other senescent cell types. Neither passage reports senolytic treatment in fish or salamanders, so the species-specific claim is unsupported by this source (page numbers unavailable in our copy). (LLM, conf=0.83)

  cites [117] sourceExperimental — accuracy not yet measured
• Supported

  The Results section on senolytic treatment reports that dasatinib and quercetin reduced senescence markers in aged killifish; the subsequent neuroregeneration Results section reports improved regeneration after injury. This supports using targeted senescent-cell reduction to assess senescence’s role in fish. The salamander portion is attached to other citations, not this source. (LLM, conf=0.88)

  cites [126] source

In the paper

“Advances in high-throughput imaging, computational tools, and machine learning have fostered the use of multiparameter morphological analysis as a robust, unbiased, and quantifiable marker of senescence.”

What the sources say

• ?Could not verify

  The Introduction describes a spatial-transcriptomics method that identifies senescent-cell-containing microdomains by gene-expression profiles. The ‘Analysis of ST datasets’ section identifies high-senescence spots by Cdkn2a expression. Searches for multiparameter morphological analysis and high-throughput imaging found no passage assessing morphology as a robust, unbiased, quantifiable marker of senescence; page numbers were unavailable in our copy. (LLM, conf=0.74)

  cites [140] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Data integration section discusses combining cell morphology images with expression data to identify cellular subpopulations, and the Perspectives section mentions studying ageing. Neither says that multiparameter morphological analysis is a robust, unbiased, quantifiable marker of senescence. Searches for senescence, high-throughput imaging, and morphological markers found no passage making that claim. (LLM, conf=0.76)

  cites [141] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section identifies senescent cells using SA-β-gal staining and spatial transcriptomics, while the Methods section describes automated quantification of stained areas. Neither passage establishes multiparameter morphological analysis as a robust, unbiased marker of senescence. Searches for morphological markers and high-throughput imaging with machine learning found no passage addressing that claim; page numbers were unavailable in our copy. (LLM, conf=0.75)

  cites [142] sourceExperimental — accuracy not yet measured

In the paper

“For example, several vertebrate groups, including fish and amphibians, lack p16122,125.”

What the sources say

• ?Could not verify

  The Introduction discusses regeneration in zebrafish and salamanders, and the Results describe senescence in salamander cells, but neither addresses whether these animals lack p16. Searches for p16 and its absence in fish and amphibians found p16 only in reference titles, not a statement supporting the claim. No page numbers are available in our copy. (LLM, conf=0.75)

  cites [122] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results/Discussion passage (page unavailable) reports expression of cdkn1a and cdkn2ab during zebrafish fin regeneration, but does not say whether fish lack p16. Searches for p16 and for its absence in fish and amphibians found no passage addressing the claim about vertebrate groups. (LLM, conf=0.72)

  cites [125] sourceExperimental — accuracy not yet measured

In the paper

“Although it remains unclear whether cancer cell senescence is irreversible, primary cancer therapeutics that trigger a senescence-like phenotype in cancer cells allow further targeting of these cells using a one-two-punch approach (senescence-senolysis) to eliminate surviving cancer cells148,149.”

What the sources say

• Supported

  The Results section (‘Characterization of drugs that induce senescence specifically in cancer cells’) explicitly describes combining senescence-inducing drugs with a senolytic as a ‘one-two punch’ approach to target cancer cells. It also reports that pretreatment with the tested drugs sensitized A549 cancer cells to the senolytic ABT-263. (LLM, conf=0.91)

  cites [148] source
• Partly supported

  The Discussion (page unavailable) says cancer treatment can induce senescent cells, supporting the first step of the claim. It does not say that those cells are surviving cancer cells that can then be eliminated through senolysis, or describe a one-two-punch treatment approach. (LLM, conf=0.82)

  cites [149] sourceExperimental — accuracy not yet measured

In the paper

“These new senescence classifiers can detect senescence in vivo in aging, fibrosis, preclinical models of cancer140,141, and a range of clinical samples141,142.”

What the sources say

• Partly supported

  The Introduction describes a spatial-transcriptomics method that identifies senescent-cell-containing microdomains in aged mouse brains, supporting detection in an aging model. The Results show Cdkn2a-positive spots in those brains, but the paper does not establish that senescence classifiers detect senescence in fibrosis, preclinical cancer models, or clinical samples. It also cautions that its spatial-transcriptomics spots cannot resolve individual cells. (LLM, conf=0.83)

  cites [140] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Single-cell genomics-plus-transcriptomics section discusses cancer cell states and how multi-omics methods may help study ageing, but it does not discuss senescence classifiers. Searches for senescence classifiers, fibrosis, and detection in clinical samples found no passage supporting the attributed claim. (LLM, conf=0.75)

  cites [141] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section, “Clinical predictions based on the assessment of epithelial and mesenchymal SMCCs,” describes classifying senescence-associated cell states in human colorectal liver metastasis samples and assessing signatures in a colorectal cancer cohort. This supports detection in clinical cancer samples. Our copy does not show these classifiers detecting senescence in aging, fibrosis, or preclinical cancer models; those parts of the citing sentence are not supported by this source. (LLM, conf=0.85)

  cites [142] sourceExperimental — accuracy not yet measured

In the paper

“The availability of SA-β-gal as a senescence marker outside mammalian systems has also enabled the use of galacto-nanoparticles127 to label, isolate, or eliminate SA-β-gal cells in vivo when delivered systemically126.”

What the sources say

• Partly supported

  The Results (‘Senescence precedes regenerative reprogramming’; page not provided) identify SAβ-Gal activity as a senescence indicator in the cnidarian Hydractinia. The Methods (‘SpiDER-Gal staining’; page not provided) describe staining live animals with a fluorescent probe, but the paper does not report galacto-nanoparticles or their systemic delivery to label, isolate, or eliminate cells. (LLM, conf=0.88)

  cites [127] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section on cellular phenotyping identifies SA-β-gal as a senescence marker in killifish. The Results section on systemic treatment reports that injected dasatinib and quercetin reduced SA-β-gal-positive cells, but it does not report systemic delivery of galacto-nanoparticles or their use to label, isolate, or eliminate those cells. (LLM, conf=0.86)

  cites [126] sourceExperimental — accuracy not yet measured

In the paper

“Some biochemical markers of senescence, including lack of incorporation of thymidine analogues as a reporter of reduced proliferation or increased ROS abundance and macromolecular oxidative damage, are established for several species119,120,124.”

What the sources say

• ?Not checked — no full text of the sourcecites [119] source
• ?Could not verify

  The Intracellular Molecules section discusses genetically modified rats and cellular functions, while the Conclusion and Perspectives table mentions antioxidant status in a transgenic rat model. Neither addresses senescence markers or their establishment across species. Searches for thymidine-analogue incorporation, ROS, oxidative damage, and senescence found no passage supporting the attributed claim; page numbers were unavailable. (LLM, conf=0.76)

  cites [120] sourceExperimental — accuracy not yet measured
• Partly supported

  The Methods section (‘Senescence induction and conditioned media generation’; page unavailable) identifies reduced EdU incorporation, a thymidine-analogue measure, as evidence of senescence in newt cells. The Introduction describes some senescence features as conserved between species. Neither passage establishes increased ROS abundance or macromolecular oxidative damage as markers across species. (LLM, conf=0.86)

  cites [124] sourceExperimental — accuracy not yet measured

In the paper

“Other senescence markers have been shown to be overexpressed or activated in cancer152.”

What the sources say

• Supported

  The “Senescence in human tumours” section reports senescence-marker expression in human prostate lesions, neurofibromas and colon adenomas. The “Senescence is a tumour suppressive mechanism” section also reports increased p27 expression in tumour models. The evidence chiefly concerns premalignant lesions, rather than established invasive cancers; no page numbers are available in our copy. (LLM, conf=0.87)

  cites [152] source

In the paper

“However, as cancer progresses, features of senescence are lost or mutated in cancer cells, including the expression levels of the tumor suppressor p53 and CDKN2A/CDKN2B loci gene products, p16Ink4a, p14/p19ARF, and p15INK4b.”

What the sources say

• Partly supported

  The Abstract and Discussion (page unavailable) report that treated murine lymphomas can escape senescence and acquire p53 or INK4a mutations as once-dormant tumors progress. This supports the p53/p16INK4a portion, but not a general claim about cancer progression or loss of all the listed products: the paper does not establish a corresponding progression-related loss of p15INK4b, and it distinguishes loss of ARF alone from loss of INK4a/ARF. (LLM, conf=0.87)

  cites [151] sourceExperimental — accuracy not yet measured

In the paper

“It is likely that certain senescence markers, such as those based on post-translational modifications, enzymatic activity, or protein translocations, are more sensitive to tissue collection times and fixation methods159,160.”

What the sources say

• ?Could not verify

  The Introduction describes detecting senescence-associated β-galactosidase through its enzymatic activity, and Future Prospects discusses staining non-processed tissue. Neither passage says that this or other senescence markers are more sensitive to tissue collection times or fixation methods. Searches for fixation, sample handling, post-translational modifications, and protein translocations found no passage addressing that comparison; page numbers were not available in our copy. (LLM, conf=0.73)

  cites [159] sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Methods (page not specified) describe fixation and staining protocols for the enzymatic senescence marker SA-β-gal, but do not assess whether its detection is sensitive to collection time or fixation method. No passage found addresses the claimed greater sensitivity of markers based on post-translational modifications, enzymatic activity, or protein translocations. (LLM, conf=0.76)

  cites [160] sourceExperimental — accuracy not yet measured

In the paper

“Samples from mouse models of oncogenic activation, as well as samples of benign tumors, such as prostate intraepithelial neoplasia or melanocytic nevi, are often enriched in non-proliferative senescent cells expressing all the expected senescent markers and SASP factors147.”

What the sources say

• Partly supported

  The Introduction (page unavailable) identifies loss of proliferation and SASP as senescence hallmarks. The Results, ‘Applying phenotypic profiling to senescence in vivo’ (page unavailable), report increased p21-positive cells in palbociclib-treated human tumor xenografts. These passages do not establish enrichment in mouse models of oncogenic activation or benign tumors such as prostate intraepithelial neoplasia and melanocytic nevi, nor show that those cells express all expected markers and SASP factors. (LLM, conf=0.82)

  cites [147] sourceExperimental — accuracy not yet measured

In the paper

“During the early phases of cancer progression, mutated cells display a genuine senescent phenotype, as a consequence of oncogene-induced senescence150.”

What the sources say

• Partly supported

  The “Mitogens and Proliferation-Associated Signals” section says oncogenic H-RAS and other oncogenic signals can induce genuine cellular senescence. Its example concerns normal cells, however; the passages do not establish that mutated cells display this phenotype specifically during the early phases of cancer progression. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  cites [150] sourceExperimental — accuracy not yet measured

In the paper

“Senescent cells are enriched in a wide range of human diseases and disease-associated conditions154,155.”

What the sources say

• ?Not checked — no full text of the sourcecites [154] source
• ?Could not verify

  The Introduction discusses senescent cells in tissue repair and cancer therapy, while the Results section on PARPi-treated ovarian cancer cells reports increased senescence markers after treatment. Neither passage says that senescent cells are enriched across a wide range of human diseases or disease-associated conditions. Searches for that phrase and for accumulation across multiple diseases found no supporting passage in our copy. (LLM, conf=0.74)

  cites [155] sourceExperimental — accuracy not yet measured

In the paper

“Elevated expression of p16 in melanocytes156 and epidermal and dermal cells157,158 is associated with human aging.”

What the sources say

• ?Could not verify

  The paper’s Abstract discusses p16INK4A-positive cells in treated mouse liver tumors, not p16 expression in human skin during aging. Searches for melanocytes, epidermal and dermal cells, and skin aging found no passage addressing the attributed association. (LLM, conf=0.78)

  cites [156] sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction states that p16 levels or activity increase in senescent cells and describes ras-induced senescence. It does not establish elevated p16 expression in melanocytes or epidermal and dermal cells during human aging; the cited paper’s senescence finding is narrower than that claim. (LLM, conf=0.84)

  cites [157] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [158] source

In the paper

“Finally, as clinical trials on the targeted elimination of senescent cells were initiated only relatively recently155 and the molecular targets of many senolytics are either unknown or pleiotropic, it is still unclear which markers of senescence are most informative about the burden of senescence in humans.”

What the sources say

• ?Could not verify

  The Results section on PARP-inhibitor-treated ovarian cancer cells describes senescence-associated markers, including SA-β-galactosidase, cell enlargement, and secreted IL-6 and IL-8 (page unavailable). It does not assess which markers best indicate the burden of senescence in humans. Searches for human senescence burden, clinical biomarkers, and marker uncertainty found no passage addressing that question. (LLM, conf=0.72)

  cites [155] sourceExperimental — accuracy not yet measured

In the paper

“Senescent cancer cells express numerous markers of cellular senescence, including cell cycle inhibitors, SASP factors, and SA-β-gal147.”

What the sources say

• Partly supported

  The Introduction (page not provided) lists tumour-suppressor expression, SASP and SA-β-Gal activity as markers of cellular senescence generally. In Results, “Applying phenotypic profiling to senescence in vivo” (page not provided), the paper identifies p21-positive cells in a human tumour xenograft, but does not show that those cancer cells also express SASP factors or SA-β-Gal. The claim extends the general marker list to senescent cancer cells without support for all three markers in that population. (LLM, conf=0.86)

  cites [147] sourceExperimental — accuracy not yet measured

In the paper

“DSBs can occur anywhere in chromosomes, but cellular senescence is associated with their preferential accumulation at telomeres because of the limited repair of telomeric DNA (Fig. 1 E).”

In the paper

“downregulation of LMNB1 expression is currently the most suitable nuclear envelope marker for in situ measurement of cellular senescence.”

In the paper

“Currently, the most robust DDR markers employed in senescence studies are the phosphorylated forms of H2A histone family member X (γ-H2A.X) and p53-binding protein 1 (53BP1).”

In the paper

“Although p14/19Arf and p16Ink4a have no overlapping amino acid sequences owing to the different reading frames of the transcripts, the detection of the p16Ink4a protein has proven difficult in mouse tissues.”

In the paper

“Thus, the average frequency of SADS events per cell represents senescence more accurately than the number of positive cells does.”

In the paper

“there are currently no easily accessible tools that allow researchers to provide evidence of persistent cell cycle arrest.”

In the paper

“Similar to other senescence markers, a major limitation of SA-β-gal is that it may reflect a wide range of metabolic adaptations of lysosomes, not only those occurring during senescence.”

In the paper

“Alteration of physiology in senescent cells leads to metabolic adjustments, which include an increase in the number and/or size of lipid droplets (LDs; Fig. 1 H), a phenotype termed ALISE (Accumulation of Lipids In Senescence)31.”

What the sources say

• ?Not checked — no full text of the sourcecites [31] source

In the paper

“However, these methods do not reveal the origin of the factors, whether they are secreted by senescent cells or by other cell types, including immune cells.”

In the paper

“Thus, during senescence, γ-H2A.X accumulates, making it a suitable marker for immunohistochemistry (IHC) and IHF, but also for methods relying on tissue homogenates, such as WB.”

In the paper

“As mentioned previously, the presence of LDs is not specific to senescent cells.”

In the paper

“A limitation for the use of LMNB1 as a marker of senescence is its variable baseline expression among different cell types, which makes the definition of “positive” and “negative” rather arbitrary.”

In the paper

“Another major challenge in establishing a single SASP factor as a reliable marker of senescence in vivo is that the secretory phenotype has been demonstrated to be highly variable, dynamic, and dependent on cell type, tissue, and environmental context.”

In the paper

“assessment of senescence in skin remains challenging due to the highly histogenetically distinct populations of cell types.”

In the paper

“Therefore, we expect differences in the signature and role of the senescent phenotype across different subpopulations of skin cells.”

In the paper

“indicating that in contrast to aging, p21+ senescent cells may be more important following skeletal injury.”

In the paper

“raising questions about the suitability of this marker for the assessment of senescence in the brain.”

In the paper

“Surprisingly, most p21+ senescent cells are not p16+ in either context7.”

What the sources say

• ?Not checked — no full text of the sourcecites [7] source

In the paper

“In bronchial epithelial cells exposed to chronic inflammation, senescence is detected by increased SA-β-gal activity, p21, and γ-H2A.X levels69,70.”

What the sources say

• ?Not checked — no full text of the sourcecites [69] source
• ?Not checked — no full text of the sourcecites [70] source

In the paper

“There is evidence that various pathologies may induce different subtypes of senescent cells in the fat.”

In the paper

“following skeletal injury using radiation, clearance of p21+ senescent cells, but not p16+ senescent cells, prevents radiation-induced bone loss77”

What the sources say

• ?Not checked — no full text of the sourcecites [77] source

In the paper

“Over the past decade, several transgenic models have been developed that, unlike KO models, do not prevent senescence from occurring but rather allow the selective and timely removal of existing senescent cells.”

What the sources say

• ?Not matched

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

  cites Table 2

In the paper

“Therefore, at least some of the observed phenotypes of transgenic models with overexpression or KO of these factors might be unrelated to cellular senescence.”

In the paper

“An independent study also showed increased senescence-associated markers in myofibers in aged mice90.”

What the sources say

• ?Not checked — no full text of the sourcecites [90] source

In the paper

“Therefore, the use of native promoters in reporter mice may not always accurately reflect endogenous CDKN2A mRNA levels”

In the paper

“as their accumulation occurs on average 5–6 times faster than in wild-type mice101.”

What the sources say

• ?Not matched

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

  cites [101]

In the paper

“Several transgenic mouse models have been developed in which core modulators of senescence, such as p21 and p16, are tagged with a reporter, enabling the visualization and quantification of senescent cells in situ and in vivo (for example, see Table 2).”

What the sources say

• ?Not matched

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

  cites Table 2

In the paper

“Thus, at least some of their accelerated aging pathologies can be ascribed to mechanisms distinct from senescence.”

In the paper

“Finally, in constitutive models, it is likely that the phenotype of adult mice is affected by alterations during embryogenesis and development (dependent or independent of cellular senescence).”

In the paper

“Moreover, because these mutations increase the burden of senescent cells in vivo, this does not mean that they are the physiological source of senescence under normal conditions.”

In the paper

“Single-cell transcriptomics have revealed immense heterogeneity among senescent cells, even under relatively homogenous conditions of 2D cell culture129.”

What the sources say

• ?Not checked — no full text of the sourcecites [129] source

In the paper

“Thus, although bioinformatic approaches are powerful tools to support research on cellular senescence in vivo, they have not yet been adequately developed to replace standard methods for detecting senescence in situ or in vivo.”

In the paper

“However, caution is warranted as these signatures are not applicable to all tissues, cell types, and inducers of senescence.”

In the paper

“Given the relatively low abundance of senescent cells, single-cell approaches are likely required for senescent cell detection.”

In the paper

“This makes it practically difficult to reliably study senescence using standard, bulk omics methods, since the detection of rare cells requires technically more challenging and expensive single-cell or spatial omics approaches.”

In the paper

“Thus, unlike primary cells, which acquire senescence markers as part of their senescence stress response program, cancer cells may adopt senescence markers in a manner unrelated to their function during senescence.”

In the paper

“Unlike the cancer cells discussed below, senescence biomarkers in these non-malignant cells residing within tumors can be assessed using the same approach as for non-malignant tissues, including cell identity markers to localize them spatially.”

In the paper

“However, given the ethical concerns associated with human tissues and the fact that they are often not collected in the research laboratory, it is challenging to collect, properly preserve, and stabilize human tissues in a standardized manner, leading to increased variability in the post hoc analyses of macromolecules and metabolites.”

In the paper

“Assessing and interpreting senescence in human samples is challenging for multiple reasons, beyond biospecimen handling.”

In the paper

“Thus, it is unclear whether and how single biomarkers or signatures of biomarkers in these fluids would correlate with senescent cell burden in organs and tissues.”

In the paper

“While we currently do not have the tools to clearly define a cancer cell as senescent, we recommend using a combination of senescence markers for the detection and quantification of senescence in cancer.”

In the paper

“In principle, well-preserved human samples can be analyzed using the same set of senescence markers developed for mice.”