SenNet recommendations for detecting senescent cells in different tissues.

He, S. & Sharpless, N. E. Senescence in health and disease. Cell 169, 1000–1011 (2017).

pubmed: 28575665 pmcid: 5643029 doi: 10.1016/j.cell.2017.05.015

Muñoz-Espín, D. et al. Programmed cell senescence during mammalian embryonic development. Cell 155, 1104–1118 (2013).

pubmed: 24238962 doi: 10.1016/j.cell.2013.10.019

Storer, M. et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119–1130 (2013).

pubmed: 24238961 doi: 10.1016/j.cell.2013.10.041

Di Micco, R., Krizhanovsky, V., Baker, D. & d’Adda di Fagagna, F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 22, 75–95 (2021).

pubmed: 33328614 doi: 10.1038/s41580-020-00314-w

Demaria, M. et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 7, 165–176 (2017).

pubmed: 27979832 doi: 10.1158/2159-8290.CD-16-0241

Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685–705 (2013).

pubmed: 23140366 doi: 10.1146/annurev-physiol-030212-183653

Ovadya, Y. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat. Commun. 9, 5435 (2018).

pubmed: 30575733 pmcid: 6303397 doi: 10.1038/s41467-018-07825-3

Karin, O., Agrawal, A., Porat, Z., Krizhanovsky, V. & Alon, U. Senescent cell turnover slows with age providing an explanation for the Gompertz law. Nat. Commun. 10, 5495 (2019).

pubmed: 31792199 pmcid: 6889273 doi: 10.1038/s41467-019-13192-4

Onorati, A. et al. Upregulation of PD-L1 in senescence and aging. Mol. Cell. Biol. 42, e0017122 (2022).

pubmed: 36154662 doi: 10.1128/mcb.00171-22

Wang, T.-W. et al. Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes. Nature 611, 358–364 (2022).

pubmed: 36323784 doi: 10.1038/s41586-022-05388-4

SenNet Consortium NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. Nat. Aging 2, 1090–1100 (2022).

pmcid: 10019484 doi: 10.1038/s43587-022-00326-5

Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes. Dev. 28, 99–114 (2014).

pubmed: 24449267 pmcid: 3909793 doi: 10.1101/gad.235184.113

Lessard, F. et al. Senescence-associated ribosome biogenesis defects contributes to cell cycle arrest through the Rb pathway. Nat. Cell Biol. 20, 789–799 (2018).

pubmed: 29941930 doi: 10.1038/s41556-018-0127-y

Rodier, F. & Campisi, J. Four faces of cellular senescence. J. Cell Biol. 192, 547–556 (2011).

pubmed: 21321098 pmcid: 3044123 doi: 10.1083/jcb.201009094

Sharpless, N. E. & Sherr, C. J. Forging a signature of in vivo senescence. Nat. Rev. Cancer 15, 397–408 (2015).

pubmed: 26105537 doi: 10.1038/nrc3960

Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018).

pubmed: 29477613 doi: 10.1016/j.tcb.2018.02.001

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

pubmed: 31675495 doi: 10.1016/j.cell.2019.10.005

Fafián-Labora, J. A., Rodríguez-Navarro, J. A. & O’Loghlen, A. Small extracellular vesicles have GST activity and ameliorate senescence-related tissue damage. Cell Metab. 32, 71–86.e5 (2020).

pubmed: 32574561 pmcid: 7342013 doi: 10.1016/j.cmet.2020.06.004

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

pubmed: 28585531 pmcid: 5467215 doi: 10.1038/ncomms15728

Meng, Q. et al. Surfaceome analysis of extracellular vesicles from senescent cells uncovers uptake repressor DPP4. Proc. Natl Acad. Sci. USA 120, e2219801120 (2023).

pubmed: 37862381 pmcid: 10614838 doi: 10.1073/pnas.2219801120

Wiley, C. D. & Campisi, J. The metabolic roots of senescence: mechanisms and opportunities for intervention. Nat. Metab. 3, 1290–1301 (2021).

pubmed: 34663974 pmcid: 8889622 doi: 10.1038/s42255-021-00483-8

Wiley, C. D. et al. Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence. Aging Cell 16, 1043–1050 (2017).

pubmed: 28699239 pmcid: 5595671 doi: 10.1111/acel.12632

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

pubmed: 30728521 pmcid: 6519963 doi: 10.1038/s41586-018-0784-9

Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978–990 (2013).

pubmed: 23770676 pmcid: 3732483 doi: 10.1038/ncb2784

Teo, Y. V. et al. Notch signaling mediates secondary senescence. Cell Rep. 27, 997–1007.e5 (2019).

pubmed: 31018144 pmcid: 6486482 doi: 10.1016/j.celrep.2019.03.104

Evans S. A. et al. Single-cell transcriptomics reveals global markers of transcriptional diversity across different forms of cellular senescence. AgingBio 1, 1–13 (2023).

Cruickshanks, H. A. et al. Senescent cells harbour features of the cancer epigenome. Nat. Cell Biol. 15, 1495–1506 (2013).

pubmed: 24270890 pmcid: 4106249 doi: 10.1038/ncb2879

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).

pubmed: 23360310 doi: 10.1111/acel.12047

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

pubmed: 24344186 pmcid: 3871423 doi: 10.1083/jcb.201306073

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).

pubmed: 23934658 pmcid: 3759695 doi: 10.1101/gad.223834.113

Chandra, T. et al. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol. Cell 47, 203–214 (2012).

pubmed: 22795131 pmcid: 3701408 doi: 10.1016/j.molcel.2012.06.010

Vernier, M. et al. Regulation of E2Fs and senescence by PML nuclear bodies. Genes. Dev. 25, 41–50 (2011).

pubmed: 21205865 pmcid: 3012935 doi: 10.1101/gad.1975111

Rouillard, M. E. et al. The cellular senescence factor extracellular HMGB1 directly inhibits oligodendrocyte progenitor cell differentiation and impairs CNS remyelination. Front. Cell. Neurosci. 16, 833186 (2022).

pubmed: 35573828 pmcid: 9095917 doi: 10.3389/fncel.2022.833186

Althubiti, M. et al. Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death Dis. 5, e1528 (2014).

pubmed: 25412306 pmcid: 4260747 doi: 10.1038/cddis.2014.489

Rossi, M. & Abdelmohsen, K. The emergence of senescent surface biomarkers as senotherapeutic targets. Cells 10, 1740 (2021).

pubmed: 34359910 pmcid: 8305747 doi: 10.3390/cells10071740

Reimann, M. et al. Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas. Blood 137, 2785–2799 (2021).

pubmed: 33232972 doi: 10.1182/blood.2020005244

Marin, I. et al. Cellular senescence is immunogenic and promotes antitumor immunity. Cancer Discov. 13, 410–431 (2023).

pubmed: 36302218 doi: 10.1158/2159-8290.CD-22-0523

Chen, H.-A. et al. Senescence rewires microenvironment sensing to facilitate antitumor immunity. Cancer Discov. 13, 432–453 (2023).

pubmed: 36302222 doi: 10.1158/2159-8290.CD-22-0528

Biran, A. et al. Senescent cells communicate via intercellular protein transfer. Genes. Dev. 29, 791–802 (2015).

pubmed: 25854920 pmcid: 4403256 doi: 10.1101/gad.259341.115

Ivanov, A. et al. Lysosome-mediated processing of chromatin in senescence. J. Cell Biol. 202, 129–143 (2013).

pubmed: 23816621 pmcid: 3704985 doi: 10.1083/jcb.201212110

Dou, Z. et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550, 402–406 (2017).

pubmed: 28976970 pmcid: 5850938 doi: 10.1038/nature24050

Park, J. T., Lee, Y.-S., Cho, K. A. & Park, S. C. Adjustment of the lysosomal–mitochondrial axis for control of cellular senescence. Ageing Res. Rev. 47, 176–182 (2018).

pubmed: 30142381 doi: 10.1016/j.arr.2018.08.003

Evangelou, K. & Gorgoulis, V. G. Sudan Black B, the specific histochemical stain for lipofuscin: a novel method to detect senescent cells. Methods Mol. Biol. 1534, 111–119 (2017).

pubmed: 27812872 doi: 10.1007/978-1-4939-6670-7_10

Quijano, C. et al. Oncogene-induced senescence results in marked metabolic and bioenergetic alterations. Cell Cycle 11, 1383–1392 (2012).

pubmed: 22421146 pmcid: 3350879 doi: 10.4161/cc.19800

Kaplon, J. et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109–112 (2013).

pubmed: 23685455 doi: 10.1038/nature12154

Dörr, J. R. et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501, 421–425 (2013).

pubmed: 23945590 doi: 10.1038/nature12437

Miwa, S., Kashyap, S., Chini, E. & von Zglinicki, T. Mitochondrial dysfunction in cell senescence and aging. J. Clin. Invest. 132, e158447 (2022).

pubmed: 35775483 pmcid: 9246372 doi: 10.1172/JCI158447

Takahashi, A. et al. Mitogenic signalling and the p16

pubmed: 17028578 doi: 10.1038/ncb1491

Victorelli, S. & Passos, J. F. Reactive oxygen species detection in senescent cells. Methods Mol. Biol. 1896, 21–29 (2019).

pubmed: 30474836 doi: 10.1007/978-1-4939-8931-7_3

Victorelli, S. et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature 622, 627–636 (2023).

pubmed: 37821702 pmcid: 10584674 doi: 10.1038/s41586-023-06621-4

Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol. 11, 973–979 (2009).

pubmed: 19597488 pmcid: 2743561 doi: 10.1038/ncb1909

von Zglinicki, T., Saretzki, G., Ladhoff, J., d’Adda di Fagagna, F. & Jackson, S. P. Human cell senescence as a DNA damage response. Mech. Ageing Dev. 126, 111–117 (2005).

doi: 10.1016/j.mad.2004.09.034

d’Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

pubmed: 14608368 doi: 10.1038/nature02118

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).

pubmed: 22426229 doi: 10.1038/ncomms1708

Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015).

pubmed: 25754370 pmcid: 4531078 doi: 10.1111/acel.12344

Doolittle, M. L. et al. Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton. Nat. Commun. 14, 4587 (2023).

pubmed: 37524694 pmcid: 10390564 doi: 10.1038/s41467-023-40393-9

Martin, N., Huna, A., Tsalikis, A. & Bernard, D. Revisiting sensitivity of senescent cells to BH3 mimetics. Trends Pharmacol. Sci. 45, 287–289 (2024).

pubmed: 38245492 doi: 10.1016/j.tips.2024.01.002

Gasek, N. S., Kuchel, G. A., Kirkland, J. L. & Xu, M. Strategies for targeting senescent cells in human disease. Nat. Aging 1, 870–879 (2021).

pubmed: 34841261 pmcid: 8612694 doi: 10.1038/s43587-021-00121-8

Ogrodnik, M., Salmonowicz, H., Jurk, D. & Passos, J. F. Expansion and cell-cycle arrest: common denominators of cellular senescence. Trends Biochem. Sci. 44, 996–1008 (2019).

pubmed: 31345557 doi: 10.1016/j.tibs.2019.06.011

Anderson, R. et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 38, e100492 (2019).

pubmed: 30737259 pmcid: 6396144 doi: 10.15252/embj.2018100492

Martini, H. et al. Aging induces cardiac mesenchymal stromal cell senescence and promotes endothelial cell fate of the CD90

pubmed: 31353772 pmcid: 6718537 doi: 10.1111/acel.13015

Lewis-McDougall, F. C. et al. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell 18, e12931 (2019).

pubmed: 30854802 pmcid: 6516154 doi: 10.1111/acel.12931

Bhayadia, R., Schmidt, B. M., Melk, A. & Homme, M. Senescence-induced oxidative stress causes endothelial dysfunction. J. Gerontol. A Biol. Sci. Med. Sci. 71, 161–169 (2016).

pubmed: 25735595 doi: 10.1093/gerona/glv008

Gao, P. et al. Transcriptome analysis of mouse aortae reveals multiple novel pathways regulated by aging. Aging 12, 15603–15623 (2020).

pubmed: 32805724 pmcid: 7467355 doi: 10.18632/aging.103652

Yu, H. et al. Role of the cGAS–STING pathway in aging-related endothelial dysfunction. Aging Dis. 13, 1901–1918 (2022).

pubmed: 36465181 pmcid: 9662267 doi: 10.14336/AD.2022.0316

Bloom, S. I. et al. Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions. Geroscience 44, 2741–2755 (2022).

pubmed: 36350415 pmcid: 9768045 doi: 10.1007/s11357-022-00681-6

Walaszczyk, A. et al. Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction. Aging Cell 18, e12945 (2019).

pubmed: 30920115 pmcid: 6516151 doi: 10.1111/acel.12945

Zhu, F. et al. Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial infarction. PLoS ONE 8, e74535 (2013).

pubmed: 24040275 pmcid: 3770549 doi: 10.1371/journal.pone.0074535

Aschacher, T. et al. Impacts of telomeric length, chronic hypoxia, senescence, and senescence-associated secretory phenotype on the development of thoracic aortic aneurysm. Int. J. Mol. Sci. 23, 15498 (2022).

pubmed: 36555139 pmcid: 9779024 doi: 10.3390/ijms232415498

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

pubmed: 27650558 pmcid: 6546422 doi: 10.1161/CIRCRESAHA.116.308895

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

pubmed: 27789842 pmcid: 5112585 doi: 10.1126/science.aaf6659

Matthews, C. et al. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res. 99, 156–164 (2006).

pubmed: 16794190 doi: 10.1161/01.RES.0000233315.38086.bc

Weiskopf, D., Weinberger, B. & Grubeck-Loebenstein, B. The aging of the immune system. Transpl. Int. 22, 1041–1050 (2009).

pubmed: 19624493 doi: 10.1111/j.1432-2277.2009.00927.x

Martínez-Zamudio, R. I. et al. Senescence-associated β-galactosidase reveals the abundance of senescent CD8

pubmed: 33939265 pmcid: 8135084 doi: 10.1111/acel.13344

Goldberg, E. L. & Dixit, V. D. Drivers of age-related inflammation and strategies for healthspan extension. Immunol. Rev. 265, 63–74 (2015).

pubmed: 25879284 pmcid: 4400872 doi: 10.1111/imr.12295

Park, M. D., Silvin, A., Ginhoux, F. & Merad, M. Macrophages in health and disease. Cell 185, 4259–4279 (2022).

pubmed: 36368305 pmcid: 9908006 doi: 10.1016/j.cell.2022.10.007

Camell, C. D. et al. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 550, 119–123 (2017).

pubmed: 28953873 pmcid: 5718149 doi: 10.1038/nature24022

Hall, B. M. et al. p16

pubmed: 28768895 pmcid: 5611982 doi: 10.18632/aging.101268

Goldberg, E. L. et al. IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2. Cell Metab. 33, 2277–2287.e5 (2021).

pubmed: 34473956 pmcid: 9067336 doi: 10.1016/j.cmet.2021.08.004

Konstorum, A. et al. Platelet response to influenza vaccination reflects effects of aging. Aging Cell 22, e13749 (2023).

pubmed: 36656789 pmcid: 9924941 doi: 10.1111/acel.13749

Callender, L. A. et al. Human CD8

pubmed: 29024417 doi: 10.1111/acel.12675

Guan, L., Crasta, K. C. & Maier, A. B. Assessment of cell cycle regulators in human peripheral blood cells as markers of cellular senescence. Ageing Res. Rev. 78, 101634 (2022).

pubmed: 35460888 doi: 10.1016/j.arr.2022.101634

Zhou, D., Borsa, M. & Simon, A. K. Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells. Aging Cell 20, e13316 (2021).

pubmed: 33524238 pmcid: 7884036 doi: 10.1111/acel.13316

Saul, D. et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat. Commun. 13, 4827 (2022).

pubmed: 35974106 pmcid: 9381717 doi: 10.1038/s41467-022-32552-1

Yousefzadeh, M. J. et al. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell 19, e13094 (2020).

pubmed: 31981461 pmcid: 7059165 doi: 10.1111/acel.13094

Yousefzadeh, M. J. et al. An aged immune system drives senescence and ageing of solid organs. Nature 594, 100–105 (2021).

pubmed: 33981041 pmcid: 8684299 doi: 10.1038/s41586-021-03547-7

Soerens, A. G. et al. Functional T cells are capable of supernumerary cell division and longevity. Nature 614, 762–766 (2023).

pubmed: 36653453 doi: 10.1038/s41586-022-05626-9

Liu, Y. et al. Expression of p16

pubmed: 19485966 doi: 10.1111/j.1474-9726.2009.00489.x

Wilk, C. M. et al. Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders. Immunity 56, 2790–2802.e6 (2023).

pubmed: 38091952 doi: 10.1016/j.immuni.2023.11.011

Ding, L. & Morrison, S. J. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495, 231–235 (2013).

pubmed: 23434755 pmcid: 3600153 doi: 10.1038/nature11885

Ding, L., Saunders, T. L., Enikolopov, G. & Morrison, S. J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457–462 (2012).

pubmed: 22281595 pmcid: 3270376 doi: 10.1038/nature10783

Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016).

pubmed: 26657143 doi: 10.1038/nm.4010

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

pubmed: 27341653 doi: 10.1002/jbmr.2892

Abdul-Aziz, A. M. et al. Acute myeloid leukemia induces protumoral p16

pubmed: 30401703 pmcid: 6356984 doi: 10.1182/blood-2018-04-845420

Ding, P. et al. Osteocytes regulate senescence of bone and bone marrow. eLife 11, e81480 (2022).

pubmed: 36305580 pmcid: 9678362 doi: 10.7554/eLife.81480

Li, C. J. et al. Senescent immune cells release grancalcin to promote skeletal aging. Cell Metab. 33, 1957–1973.e6 (2021).

pubmed: 34614408 doi: 10.1016/j.cmet.2021.08.009

Biavasco, R. et al. Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and histiocytosis. Nat. Commun. 12, 4559 (2021).

pubmed: 34315896 pmcid: 8316479 doi: 10.1038/s41467-021-24876-1

Bigenwald, C. et al. BRAF

pubmed: 33958797 pmcid: 9295868 doi: 10.1038/s41591-021-01304-x

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).

pubmed: 22882466 doi: 10.1111/j.1474-9726.2012.00870.x

Kiss, T. et al. Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain. Geroscience 42, 429–444 (2020).

pubmed: 32236824 pmcid: 7205992 doi: 10.1007/s11357-020-00177-1

Jin, W. N. et al. Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition. Nat. Neurosci. 24, 61–73 (2021).

pubmed: 33257875 doi: 10.1038/s41593-020-00745-w

Ogrodnik, M. et al. Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice. Aging Cell 20, e13296 (2021).

pubmed: 33470505 pmcid: 7884042 doi: 10.1111/acel.13296

Fatt, M. P. et al. Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche. Stem Cell Rep. 17, 259–275 (2022).

doi: 10.1016/j.stemcr.2021.12.010

Zhang, X. et al. Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance. Nat. Commun. 13, 5671 (2022).

pubmed: 36167854 pmcid: 9515187 doi: 10.1038/s41467-022-33226-8

Matias, I. et al. Loss of lamin-B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus. Aging Cell 21, e13521 (2022).

pubmed: 34894056 doi: 10.1111/acel.13521

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).

pubmed: 29386135 pmcid: 5806534 doi: 10.1016/j.celrep.2017.12.092

Musi, N. et al. Tau protein aggregation is associated with cellular senescence in the brain. Aging Cell 17, e12840 (2018).

pubmed: 30126037 pmcid: 6260915 doi: 10.1111/acel.12840

Dong, C. et al. ATM modulates subventricular zone neural stem cell maintenance and senescence through Notch signaling pathway. Stem Cell Res. 58, 102618 (2022).

pubmed: 34915311 doi: 10.1016/j.scr.2021.102618

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).

pubmed: 30936558 pmcid: 6605052 doi: 10.1038/s41593-019-0372-9

Bussian, T. J. et al. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562, 578–582 (2018).

pubmed: 30232451 pmcid: 6206507 doi: 10.1038/s41586-018-0543-y

Bhat, R. et al. Astrocyte senescence as a component of Alzheimer’s disease. PLoS ONE 7, e45069 (2012).

pubmed: 22984612 pmcid: 3440417 doi: 10.1371/journal.pone.0045069

Hu, Y. et al. Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology. Cell Rep. 35, 109228 (2021).

pubmed: 34107254 pmcid: 8206957 doi: 10.1016/j.celrep.2021.109228

Gaikwad, S. et al. Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer’s disease and frontotemporal dementia. Cell Rep. 36, 109419 (2021).

pubmed: 34289368 pmcid: 8341760 doi: 10.1016/j.celrep.2021.109419

Dehkordi, S. K. et al. Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Nat. Aging 1, 1107–1116 (2021).

pubmed: 35531351 pmcid: 9075501 doi: 10.1038/s43587-021-00142-3

Bryant, A. G. et al. Cerebrovascular senescence is associated with tau pathology in Alzheimer’s disease. Front. Neurol. 11, 575953 (2020).

pubmed: 33041998 pmcid: 7525127 doi: 10.3389/fneur.2020.575953

Brichta, L. et al. Identification of neurodegenerative factors using translatome-regulatory network analysis. Nat. Neurosci. 18, 1325–1333 (2015).

pubmed: 26214373 pmcid: 4763340 doi: 10.1038/nn.4070

Turnquist, C. et al. Radiation-induced astrocyte senescence is rescued by Δ133p53. Neuro. Oncol. 21, 474–485 (2019).

pubmed: 30615147 pmcid: 6422440 doi: 10.1093/neuonc/noz001

Sun, J. K. et al. Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons. Aging Cell 22, e13772 (2023).

pubmed: 36691110 pmcid: 9924945 doi: 10.1111/acel.13772

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).

pubmed: 26578790 pmcid: 4655580 doi: 10.1073/pnas.1515386112

Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018).

pubmed: 29988130 pmcid: 6082705 doi: 10.1038/s41591-018-0092-9

Palmer, A. K. et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell 18, e12950 (2019).

pubmed: 30907060 pmcid: 6516193 doi: 10.1111/acel.12950

Wang, L. et al. Targeting p21

pubmed: 34813734 doi: 10.1016/j.cmet.2021.11.002

Choudhery, M. S., Badowski, M., Muise, A., Pierce, J. & Harris, D. T. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J. Transl. Med. 12, 8 (2014).

pubmed: 24397850 pmcid: 3895760 doi: 10.1186/1479-5876-12-8

Wang, B. et al. Transplanting cells from old but not young donors causes physical dysfunction in older recipients. Aging Cell 19, e13106 (2020).

pubmed: 31971661 pmcid: 7059132 doi: 10.1111/acel.13106

Wang, B. et al. An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo. Nat. Aging 1, 962–973 (2021).

pubmed: 35024619 pmcid: 8746571 doi: 10.1038/s43587-021-00107-6

Li, Q. et al. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nat. Med. 27, 1941–1953 (2021).

pubmed: 34608330 doi: 10.1038/s41591-021-01501-8

Chini, C. C. S. et al. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD

pubmed: 33199925 pmcid: 8752031 doi: 10.1038/s42255-020-00298-z

Shirakawa, K. et al. Obesity accelerates T cell senescence in murine visceral adipose tissue. J. Clin. Invest. 126, 4626–4639 (2016).

pubmed: 27820698 pmcid: 5127667 doi: 10.1172/JCI88606

Colón-Mesa, I. et al. Regulation of p27 and cdk2 expression in different adipose tissue depots in aging and obesity. Int. J. Mol. Sci. 22, 11745 (2021).

pubmed: 34769201 pmcid: 8584112 doi: 10.3390/ijms222111745

Song, H. D. et al. Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction. Aging Dis. 11, 575–587 (2020).

pubmed: 32489703 doi: 10.14336/AD.2019.0810

Wang, J. et al. Deletion of Nrip1 extends female mice longevity, increases autophagy, and delays cell senescence. J. Gerontol. A Biol. Sci. Med. Sci. 73, 882–892 (2018).

pubmed: 29346516 pmcid: 6001896 doi: 10.1093/gerona/glx257

Moreno-Navarrete, J. M. et al. DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence. Obesity 23, 519–522 (2015).

pubmed: 25682741 doi: 10.1002/oby.20999

Ullah, M. & Sun, Z. Klotho deficiency accelerates stem cells aging by impairing telomerase activity. J. Gerontol. A Biol. Sci. Med. Sci. 74, 1396–1407 (2019).

pubmed: 30452555 doi: 10.1093/gerona/gly261

Khanh, V. C. et al. Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1. Biochem. Biophys. Res. Commun. 500, 682–690 (2018).

pubmed: 29678576 doi: 10.1016/j.bbrc.2018.04.136

Lee, G. et al. SREBP1c–PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity. Cell Metab. 34, 702–718.e5 (2022).

pubmed: 35417665 doi: 10.1016/j.cmet.2022.03.010

Moon, J. S. et al. Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice. Aging Cell 19, e13195 (2020).

pubmed: 32691494 pmcid: 7431835 doi: 10.1111/acel.13195

Liu, Z. et al. The dysfunctional MDM2–p53 axis in adipocytes contributes to aging-related metabolic complications by induction of lipodystrophy. Diabetes 67, 2397–2409 (2018).

pubmed: 30131393 doi: 10.2337/db18-0684

Wei, Z. et al. Pan-senescence transcriptome analysis identified RRAD as a marker and negative regulator of cellular senescence. Free. Radic. Biol. Med. 130, 267–277 (2019).

pubmed: 30391675 doi: 10.1016/j.freeradbiomed.2018.10.457

Qiu, X. et al. Down-regulation of guanylate binding protein 1 causes mitochondrial dysfunction and cellular senescence in macrophages. Sci. Rep. 8, 1679 (2018).

pubmed: 29374208 pmcid: 5785964 doi: 10.1038/s41598-018-19828-7

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

pubmed: 34725920 pmcid: 8573606 doi: 10.15252/emmm.202114146

Baker, D. J. et al. Naturally occurring p16

pubmed: 26840489 pmcid: 4845101 doi: 10.1038/nature16932

Prattichizzo, F. et al. Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages. Redox Biol. 15, 170–181 (2018).

pubmed: 29253812 doi: 10.1016/j.redox.2017.12.001

Fang, Y. et al. Age-related GSK3β overexpression drives podocyte senescence and glomerular aging. J. Clin. Invest. 132, e141848 (2022).

pubmed: 35166234 pmcid: 8843754 doi: 10.1172/JCI141848

Zhang, L. et al. C/EBPɑ deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice. Cell Death Dis. 10, 684 (2019).

pubmed: 31527620 pmcid: 6746733 doi: 10.1038/s41419-019-1933-2

Sis, B. et al. Accelerated expression of senescence associated cell cycle inhibitor p16

pubmed: 17183247 doi: 10.1038/sj.ki.5002039

Kitada, K. et al. Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J. Diabetes Complications 28, 604–611 (2014).

pubmed: 24996978 pmcid: 4153757 doi: 10.1016/j.jdiacomp.2014.05.010

Verzola, D. et al. Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy. Am. J. Physiol. Ren. Physiol. 295, F1563–F1573 (2008).

doi: 10.1152/ajprenal.90302.2008

Satriano, J. et al. Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes. Am. J. Physiol. Cell Physiol. 299, C374–C380 (2010).

pubmed: 20505038 pmcid: 2928628 doi: 10.1152/ajpcell.00096.2010

Kim, S. R. et al. Increased cellular senescence in the murine and human stenotic kidney: effect of mesenchymal stem cells. J. Cell. Physiol. 236, 1332–1344 (2021).

pubmed: 32657444 doi: 10.1002/jcp.29940

Westhoff, J. H. et al. Telomere shortening reduces regenerative capacity after acute kidney injury. J. Am. Soc. Nephrol. 21, 327–336 (2010).

pubmed: 19959722 pmcid: 2834551 doi: 10.1681/ASN.2009010072

Melk, A. et al. Expression of p16

pubmed: 14717921 doi: 10.1111/j.1523-1755.2004.00438.x

Chkhotua, A. B. et al. Increased expression of p16

pubmed: 12776284 doi: 10.1016/S0272-6386(03)00363-9

Melk, A. et al. Telomere shortening in kidneys with age. J. Am. Soc. Nephrol. 11, 444–453 (2000).

pubmed: 10703668 doi: 10.1681/ASN.V113444

Luo, C. et al. Wnt9a promotes renal fibrosis by accelerating cellular senescence in tubular epithelial cells. J. Am. Soc. Nephrol. 29, 1238–1256 (2018).

pubmed: 29440280 pmcid: 5875944 doi: 10.1681/ASN.2017050574

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).

pubmed: 25499914 pmcid: 4349629 doi: 10.1016/j.devcel.2014.11.012

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

pubmed: 38097808 pmcid: 10730403 doi: 10.1038/s42255-023-00928-2

Wang, C. et al. DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 8, 311–323 (2009).

pubmed: 19627270 doi: 10.1111/j.1474-9726.2009.00481.x

Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14, 355–365 (2012).

pubmed: 22426077 pmcid: 3717580 doi: 10.1038/ncb2466

Ogrodnik, M. et al. Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun. 8, 15691 (2017).

pubmed: 28608850 pmcid: 5474745 doi: 10.1038/ncomms15691

Wiemann, S. U. et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 16, 935–942 (2002).

pubmed: 12087054 doi: 10.1096/fj.01-0977com

Aravinthan, A. et al. Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease. J. Hepatol. 58, 549–556 (2013).

pubmed: 23142622 doi: 10.1016/j.jhep.2012.10.031

Wilson, C. L. et al. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma. Nat. Commun. 6, 6818 (2015).

pubmed: 25879839 doi: 10.1038/ncomms7818

Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).

pubmed: 18724938 pmcid: 3073300 doi: 10.1016/j.cell.2008.06.049

Cheng, N., Kim, K. H. & Lau, L. F. Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2. JCI Insight 7, e158207 (2022).

pubmed: 35708907 pmcid: 9431681 doi: 10.1172/jci.insight.158207

Moncsek, A. et al. Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2

pubmed: 28802066 doi: 10.1002/hep.29464

Kaur, G., Sundar, I. K. & Rahman, I. p16-3MR: a novel model to study cellular senescence in cigarette smoke-induced lung injuries. Int. J. Mol. Sci. 22, 4834 (2021).

pubmed: 34063608 pmcid: 8125702 doi: 10.3390/ijms22094834

Reyes, N. S. et al. Sentinel p16

pubmed: 36227993 pmcid: 10621323 doi: 10.1126/science.abf3326

Yao, H. et al. Timing and cell specificity of senescence drives postnatal lung development and injury. Nat. Commun. 14, 273 (2023).

pubmed: 36650158 pmcid: 9845377 doi: 10.1038/s41467-023-35985-4

Kobayashi, Y. et al. Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis. Nat. Cell Biol. 22, 934–946 (2020).

pubmed: 32661339 pmcid: 7461628 doi: 10.1038/s41556-020-0542-8

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

pubmed: 28722352 pmcid: 5595683 doi: 10.1111/acel.12643

Chen, H. et al. TGF-β1/IL-11/MEK/ERK signaling mediates senescence-associated pulmonary fibrosis in a stress-induced premature senescence model of Bmi-1 deficiency. Exp. Mol. Med. 52, 130–151 (2020).

pubmed: 31959867 pmcid: 7000795 doi: 10.1038/s12276-019-0371-7

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

pubmed: 35899478 doi: 10.1096/fj.202200406RR

Parikh, P. et al. Cellular senescence in the lung across the age spectrum. Am. J. Physiol. Lung Cell. Mol. Physiol. 316, L826–L842 (2019).

pubmed: 30785345 pmcid: 6589594 doi: 10.1152/ajplung.00424.2018

Aghali, A. et al. Cellular senescence is increased in airway smooth muscle cells of elderly persons with asthma. Am. J. Physiol. Lung Cell. Mol. Physiol. 323, L558–L568 (2022).

pubmed: 36166734 pmcid: 9639764 doi: 10.1152/ajplung.00146.2022

Kuźnar-Kamińska, B. et al. Serum from patients with chronic obstructive pulmonary disease induces senescence-related phenotype in bronchial epithelial cells. Sci. Rep. 8, 12940 (2018).

pubmed: 30154415 pmcid: 6113312 doi: 10.1038/s41598-018-31037-w

Xiaofei, Y., Tingting, L., Xuan, W. & Zhiyi, H. Erythromycin attenuates oxidative stress-induced cellular senescence via the PI3K–mTOR signaling pathway in chronic obstructive pulmonary disease. Front. Pharmacol. 13, 1043474 (2022).

pubmed: 36506578 pmcid: 9727195 doi: 10.3389/fphar.2022.1043474

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

pubmed: 31428695 pmcid: 6689060 doi: 10.1038/s42003-019-0532-1

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

pubmed: 37078230 pmcid: 10352560 doi: 10.1111/acel.13850

Sanders, J. L. et al. The association of aging biomarkers, interstitial lung abnormalities, and mortality. Am. J. Respir. Crit. Care Med. 203, 1149–1157 (2021).

pubmed: 33080140 pmcid: 8314902 doi: 10.1164/rccm.202007-2993OC

Sanders, Y. Y. et al. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur. Respir. J. 43, 1448–1458 (2014).

pubmed: 24603818 doi: 10.1183/09031936.00095113

Yosef, R. et al. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat. Commun. 7, 11190 (2016).

pubmed: 27048913 pmcid: 4823827 doi: 10.1038/ncomms11190

Aguayo-Mazzucato, C. et al. Acceleration of β cell aging determines diabetes and senolysis improves disease outcomes. Cell Metab. 30, 129–142.e4 (2019).

pubmed: 31155496 pmcid: 6610720 doi: 10.1016/j.cmet.2019.05.006

Midha, A. et al. Unique human and mouse β-cell senescence-associated secretory phenotype (SASP) reveal conserved signaling pathways and heterogeneous factors. Diabetes 70, 1098–1116 (2021).

pubmed: 33674410 pmcid: 8173799 doi: 10.2337/db20-0553

Thompson, P. J. et al. Targeted elimination of senescent β cells prevents type 1 diabetes. Cell Metab. 29, 1045–1060.e10 (2019).

pubmed: 30799288 doi: 10.1016/j.cmet.2019.01.021

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

pubmed: 34644565 pmcid: 8845126 doi: 10.1016/j.celrep.2021.109813

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

pubmed: 36375063 pmcid: 9704710 doi: 10.1073/pnas.2206923119

Brawerman, G., Ntranos, V. & Thompson, P. J. ɑ cell dysfunction in type 1 diabetes is independent of a senescence program. Front. Endocrinol. 13, 932516 (2022).

doi: 10.3389/fendo.2022.932516

Pinho, A. V. et al. Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis. Gut 60, 958–966 (2011).

pubmed: 21193456 doi: 10.1136/gut.2010.225920

Rooman, I. & Real, F. X. Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation and development? Gut 61, 449–458 (2012).

pubmed: 21730103 doi: 10.1136/gut.2010.235804

Grabliauskaite, K. et al. p21

pubmed: 25212177 doi: 10.1002/path.4440

Horiguchi, M. et al. Senescence caused by inactivation of the homeodomain transcription factor Pdx1 in adult pancreatic acinar cells in mice. FEBS Lett. 593, 2226–2234 (2019).

pubmed: 31240701 doi: 10.1002/1873-3468.13504

Kim, S. et al. The basic helix–loop–helix transcription factor E47 reprograms human pancreatic cancer cells to a quiescent acinar state with reduced tumorigenic potential. Pancreas 44, 718–727 (2015).

pubmed: 25894862 pmcid: 4464938 doi: 10.1097/MPA.0000000000000328

Tourlakis, M. E. et al. In vivo senescence in the Sbds-deficient murine pancreas: cell-type specific consequences of translation insufficiency. PLoS Genet. 11, e1005288 (2015).

pubmed: 26057580 pmcid: 4461263 doi: 10.1371/journal.pgen.1005288

Hu, C. et al. The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis. Comput. Struct. Biotechnol. J. 19, 6375–6385 (2021).

pubmed: 34938413 pmcid: 8649580 doi: 10.1016/j.csbj.2021.11.031

Luttges, J. et al. Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution. Virchows Arch. 435, 461–468 (1999).

pubmed: 10592048 doi: 10.1007/s004280050428

Aguirre, A. J. et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes. Dev. 17, 3112–3126 (2003).

pubmed: 14681207 pmcid: 305262 doi: 10.1101/gad.1158703

Miyasaka, Y. et al. Senescence in intraductal papillary mucinous neoplasm of the pancreas. Hum. Pathol. 42, 2010–2017 (2011).

pubmed: 21733551 doi: 10.1016/j.humpath.2011.03.007

Kim, H.-N. et al. Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice. Aging Cell 18, e12923 (2019).

pubmed: 30773784 pmcid: 6516158 doi: 10.1111/acel.12923

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

pubmed: 29101351 pmcid: 5670205 doi: 10.1038/s41467-017-01509-0

Saul, D. et al. Modulation of fracture healing by the transient accumulation of senescent cells. eLife 10, e69958 (2021).

pubmed: 34617510 pmcid: 8526061 doi: 10.7554/eLife.69958

Liu, J. et al. Age-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice. J. Clin. Invest. 132, e148073 (2022).

pubmed: 35426372 pmcid: 9012290 doi: 10.1172/JCI148073

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

pubmed: 32023351 doi: 10.1002/jbmr.3978

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

pubmed: 35363946 pmcid: 9124310 doi: 10.1111/acel.13602

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

pubmed: 32267250 pmcid: 7253018 doi: 10.1172/jci.insight.135236

Farr, J. N. et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat. Med. 23, 1072–1079 (2017).

pubmed: 28825716 pmcid: 5657592 doi: 10.1038/nm.4385

Farr, J. N. et al. Local senolysis in aged mice only partially replicates the benefits of systemic senolysis. J. Clin. Invest. 133, e162519 (2023).

pubmed: 36809340 pmcid: 10104901 doi: 10.1172/JCI162519

Hudgins, A. D. et al. Age- and tissue-specific expression of senescence biomarkers in mice. Front. Genet. 9, 59 (2018).

pubmed: 29527222 pmcid: 5829053 doi: 10.3389/fgene.2018.00059

Dimri, G. P. A biomarker that identifies senescenet human cells in culture and aging skin in vitro. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995).

pubmed: 7568133 pmcid: 40985 doi: 10.1073/pnas.92.20.9363

Contrepois, K. et al. Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression. Nat. Commun. 8, 14995 (2017).

pubmed: 28489069 pmcid: 5436145 doi: 10.1038/ncomms14995

Rube, C. E. et al. Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis. NPJ Aging Mech. Dis. 7, 7 (2021).

pubmed: 33795696 pmcid: 8016850 doi: 10.1038/s41514-021-00060-z

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).

pubmed: 19053174 doi: 10.1371/journal.pbio.0060301

Waldera Lupa, D. M. et al. Characterization of skin aging-associated secreted proteins (SAASP) produced by dermal fibroblasts isolated from intrinsically aged human skin. J. Invest. Dermatol. 135, 1954–1968 (2015).

pubmed: 25815425 doi: 10.1038/jid.2015.120

Victorelli, S. et al. Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction. EMBO J. 38, e101982 (2019).

pubmed: 31633821 pmcid: 6885734 doi: 10.15252/embj.2019101982

Schafer, M. J. et al. The senescence-associated secretome as an indicator of age and medical risk. JCI Insight 5, e133668 (2020).

pubmed: 32554926 pmcid: 7406245 doi: 10.1172/jci.insight.133668

Farsam, V. et al. Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration. Oncotarget 7, 83554–83569 (2016).

pubmed: 27907906 pmcid: 5347788 doi: 10.18632/oncotarget.13446

Berneburg, M. et al. Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin. J. Invest. Dermatol. 122, 1277–1283 (2004).

pubmed: 15140232 doi: 10.1111/j.0022-202X.2004.22502.x

Wang, A. S., Ong, P. F., Chojnowski, A., Clavel, C. & Dreesen, O. Loss of lamin B1 is a biomarker to quantify cellular senescence in photoaged skin. Sci. Rep. 7, 15678 (2017).

pubmed: 29142250 pmcid: 5688158 doi: 10.1038/s41598-017-15901-9

Goorochurn, R. et al. Biological processes in solar lentigo: insights brought by experimental models. Exp. Dermatol. 25, 174–177 (2016).

pubmed: 26739821 doi: 10.1111/exd.12937

Zhang, K., Anumanthan, G., Scheaffer, S. & Cornelius, L. A. HMGB1/RAGE mediates UVB-induced secretory inflammatory response and resistance to apoptosis in human melanocytes. J. Invest. Dermatol. 139, 202–212 (2019).

pubmed: 30030153 doi: 10.1016/j.jid.2018.05.035

Jo, K. et al. An anthocyanin-enriched extract from vaccinium uliginosum improves signs of skin aging in UVB-induced photodamage. Antioxidants 9, 844 (2020).

pubmed: 32916932 pmcid: 7554747 doi: 10.3390/antiox9090844

Kong, S. et al. Preparation of cod skin collagen peptides/chitosan-based temperature-sensitive gel and its anti-photoaging effect in skin. Drug. Des. Devel. Ther. 17, 419–437 (2023).

pubmed: 36798808 pmcid: 9926988 doi: 10.2147/DDDT.S391812

Quan, T. et al. Dermal fibroblast CCN1 expression in mice recapitulates human skin dermal aging. J. Invest. Dermatol. 141, 1007–1016 (2020).

pubmed: 32800875 pmcid: 7881053 doi: 10.1016/j.jid.2020.07.019

Alimirah, F. et al. Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/42MAPK signaling. Cancer Res. 80, 3606–3619 (2020).

pubmed: 32641409 pmcid: 7484313 doi: 10.1158/0008-5472.CAN-20-0108

Burd, C. E. et al. Monitoring tumorigenesis and senescence in vivo with a p16

pubmed: 23332765 pmcid: 3718011 doi: 10.1016/j.cell.2012.12.010

Michaloglou, C. et al. BRAF

pubmed: 16079850 doi: 10.1038/nature03890

Pollock, P. M. et al. High frequency of BRAF mutations in nevi. Nat. Genet. 33, 19–20 (2003).

pubmed: 12447372 doi: 10.1038/ng1054

Hugdahl, E., Kalvenes, M. B., Puntervoll, H. E., Ladstein, R. G. & Akslen, L. A. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. Br. J. Cancer 114, 801–808 (2016).

pubmed: 26924424 pmcid: 4984864 doi: 10.1038/bjc.2016.44

Pellegrini, P. et al. Constitutive activation of RANK disrupts mammary cell fate leading to tumorigenesis. Stem Cell 31, 1954–1965 (2013).

doi: 10.1002/stem.1454

Benitez, S. et al. RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness. Dev. Cell 56, 1727–1741.e7 (2021).

pubmed: 34004159 pmcid: 8221814 doi: 10.1016/j.devcel.2021.04.022

Dong, Q. et al. Aging is associated with an expansion of CD49f

pubmed: 27852980 pmcid: 5191868 doi: 10.18632/aging.101082

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

pubmed: 33378681 pmcid: 7898263 doi: 10.1016/j.celrep.2020.108566

Lemaitre, J. F. & Gaillard, J. M. Reproductive senescence: new perspectives in the wild. Biol. Rev. Camb. Philos. Soc. 92, 2182–2199 (2017).

pubmed: 28374548 doi: 10.1111/brv.12328

Dong, L., Teh, D. B. L., Kennedy, B. K. & Huang, Z. Unraveling female reproductive senescence to enhance healthy longevity. Cell Res. 33, 11–29 (2023).

pubmed: 36588114 pmcid: 9810745 doi: 10.1038/s41422-022-00718-7

Briley, S. M. et al. Reproductive age-associated fibrosis in the stroma of the mammalian ovary. Reproduction 152, 245–260 (2016).

pubmed: 27491879 pmcid: 4979755 doi: 10.1530/REP-16-0129

Lliberos, C. et al. Evaluation of inflammation and follicle depletion during ovarian ageing in mice. Sci. Rep. 11, 278 (2021).

pubmed: 33432051 pmcid: 7801638 doi: 10.1038/s41598-020-79488-4

Amargant, F. et al. Ovarian stiffness increases with age in the mammalian ovary and depends on collagen and hyaluronan matrices. Aging Cell 19, e13259 (2020).

pubmed: 33079460 pmcid: 7681059 doi: 10.1111/acel.13259

Zhang, Z., Schlamp, F., Huang, L., Clark, H. & Brayboy, L. Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary. Reproduction 159, 325–337 (2020).

pubmed: 31940276 pmcid: 7066623 doi: 10.1530/REP-19-0330

Krishnamurthy, J. et al. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299–1307 (2004).

pubmed: 15520862 pmcid: 524230 doi: 10.1172/JCI22475

Ansere, V. A. et al. Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion. Mech. Ageing Dev. 194, 111425 (2021).

pubmed: 33383072 doi: 10.1016/j.mad.2020.111425

Liu, M. et al. Cell-free fat extract improves ovarian function and fertility in mice with advanced age. Front. Endocrinol. 13, 912648 (2022).

doi: 10.3389/fendo.2022.912648

Shen, L. et al. CCL5 secreted by senescent theca-interstitial cells inhibits preantral follicular development via granulosa cellular apoptosis. J. Cell. Physiol. 234, 22554–22564 (2019).

pubmed: 31111482 doi: 10.1002/jcp.28819

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

pubmed: 35693700 pmcid: 9187433 doi: 10.1155/2022/9144644

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

pubmed: 36648735 pmcid: 10400526 doi: 10.1007/s11357-023-00728-2

Zhu, J. et al. Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice. Free. Radic. Biol. Med. 193, 511–525 (2022).

pubmed: 36336229 doi: 10.1016/j.freeradbiomed.2022.10.324

Su, X. et al. Effect of Jiajian Guishen Formula on the senescence-associated heterochromatic foci in mouse ovaria after induction of premature ovarian aging by the endocrine-disrupting agent 4-vinylcyclohexene diepoxide. J. Ethnopharmacol. 269, 113720 (2021).

pubmed: 33358858 doi: 10.1016/j.jep.2020.113720

Lengyel, E. et al. A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing. Cell Rep. 41, 111838 (2022).

pubmed: 36543131 doi: 10.1016/j.celrep.2022.111838

Velicky, P. et al. Genome amplification and cellular senescence are hallmarks of human placenta development. PLoS Genet. 14, e1007698 (2018).

pubmed: 30312291 pmcid: 6200260 doi: 10.1371/journal.pgen.1007698

Cindrova-Davies, T., Fogarty, N. M. E., Jones, C. J. P., Kingdom, J. & Burton, G. J. Evidence of oxidative stress-induced senescence in mature, post-mature and pathological human placentas. Placenta 68, 15–22 (2018).

pubmed: 30055665 pmcid: 6083404 doi: 10.1016/j.placenta.2018.06.307

Higuchi, S. et al. Trophoblast type-specific expression of senescence markers in the human placenta. Placenta 85, 56–62 (2019).

pubmed: 31327484 doi: 10.1016/j.placenta.2019.06.377

Song, H. L. et al. Appropriate expression of P57

pubmed: 33812346 doi: 10.1530/REP-20-0638

Zhang, P. et al. p21

pubmed: 9925645 pmcid: 316389 doi: 10.1101/gad.13.2.213

Chuprin, A. et al. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes. Dev. 27, 2356–2366 (2013).

pubmed: 24186980 pmcid: 3828521 doi: 10.1101/gad.227512.113

Moore, A. G. et al. The transforming growth factor-β superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J. Clin. Endocrinol. Metab. 85, 4781–4788 (2000).

pubmed: 11134143

Wang, Y. et al. SIRT1 regulates trophoblast senescence in premature placental aging in preeclampsia. Placenta 122, 56–65 (2022).

pubmed: 35460951 doi: 10.1016/j.placenta.2022.04.001

Ishikawa, A. et al. Cell fusion mediates dramatic alterations in the actin cytoskeleton, focal adhesions, and E-cadherin in trophoblastic cells. Cytoskeleton 71, 241–256 (2014).

pubmed: 24623684 doi: 10.1002/cm.21165

Bartho, L. A., Fisher, J. J., Cuffe, J. S. M. & Perkins, A. V. Mitochondrial transformations in the aging human placenta. Am. J. Physiol. Endocrinol. Metab. 319, E981–E994 (2020).

pubmed: 32954826 doi: 10.1152/ajpendo.00354.2020

Menon, R. Human fetal membranes at term: dead tissue or signalers of parturition? Placenta 44, 1–5 (2016).

pubmed: 27452431 pmcid: 5375105 doi: 10.1016/j.placenta.2016.05.013

Bonney, E. A. et al. Differential senescence in feto-maternal tissues during mouse pregnancy. Placenta 43, 26–34 (2016).

pubmed: 27324096 pmcid: 5527294 doi: 10.1016/j.placenta.2016.04.018

Cox, L. S. & Redman, C. The role of cellular senescence in ageing of the placenta. Placenta 52, 139–145 (2017).

pubmed: 28131318 doi: 10.1016/j.placenta.2017.01.116

Wijaya, J. C., Khanabdali, R., Georgiou, H. M. & Kalionis, B. Ageing in human parturition: impetus of the gestation clock in the deciduadagger. Biol. Reprod. 103, 695–710 (2020).

pubmed: 32591788 doi: 10.1093/biolre/ioaa113

Menon, R. et al. Placental membrane aging and HMGB1 signaling associated with human parturition. Aging 8, 216–230 (2016).

pubmed: 26851389 pmcid: 4789578 doi: 10.18632/aging.100891

Rajagopalan, S. & Long, E. O. Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling. Proc. Natl Acad. Sci. USA 109, 20596–20601 (2012).

pubmed: 23184984 pmcid: 3528503 doi: 10.1073/pnas.1208248109

Liu, Z. et al. Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging. Dev. Cell 57, 1347–1368.e12 (2022).

pubmed: 35613614 doi: 10.1016/j.devcel.2022.05.004

Farfan-Labonne, B., Leff-Gelman, P., Pellon-Diaz, G. & Camacho-Arroyo, I. Cellular senescence in normal and adverse pregnancy. Reprod. Biol. 23, 100734 (2023).

pubmed: 36773450 doi: 10.1016/j.repbio.2023.100734

Davy, P., Nagata, M., Bullard, P., Fogelson, N. S. & Allsopp, R. Fetal growth restriction is associated with accelerated telomere shortening and increased expression of cell senescence markers in the placenta. Placenta 30, 539–542 (2009).

pubmed: 19359039 pmcid: 2692289 doi: 10.1016/j.placenta.2009.03.005

Guo, Y. et al. Senescence-associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15. Aging Cell 18, e13013 (2019).

pubmed: 31389184 pmcid: 6826139 doi: 10.1111/acel.13013

Faggioli, F., Velarde, M. C. & Wiley, C. D. Cellular senescence, a novel area of investigation for metastatic diseases. Cells 12, 860 (2023).

pubmed: 36980201 pmcid: 10047218 doi: 10.3390/cells12060860

Khosla, S., Farr, J. N., Tchkonia, T. & Kirkland, J. L. The role of cellular senescence in ageing and endocrine disease. Nat. Rev. Endocrinol. 16, 263–275 (2020).

pubmed: 32161396 doi: 10.1038/s41574-020-0335-y

Chaib, S., Tchkonia, T. & Kirkland, J. L. Cellular senescence and senolytics: the path to the clinic. Nat. Med. 28, 1556–1568 (2022).

pubmed: 35953721 pmcid: 9599677 doi: 10.1038/s41591-022-01923-y

Minamino, T. et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 15, 1082–1087 (2009).

pubmed: 19718037 doi: 10.1038/nm.2014

von Zglinicki, T., Wan, T. & Miwa, S. Senescence in post-mitotic cells: a driver of aging? Antioxid. Redox Signal. 34, 308–323 (2021).

doi: 10.1089/ars.2020.8048

Wu, Z., Uhl, B., Gires, O. & Reichel, C. A. A transcriptomic pan-cancer signature for survival prognostication and prediction of immunotherapy response based on endothelial senescence. J. Biomed. Sci. 30, 21 (2023).

pubmed: 36978029 pmcid: 10045484 doi: 10.1186/s12929-023-00915-5

Casella, G. et al. Transcriptome signature of cellular senescence. Nucleic Acids Res. 47, 7294–7305 (2019).

pubmed: 31251810 pmcid: 6698740 doi: 10.1093/nar/gkz555

Schleich, K. et al. H3K9me3-mediated epigenetic regulation of senescence in mice predicts outcome of lymphoma patients. Nat. Commun. 11, 3651 (2020).

pubmed: 32686676 pmcid: 7371731 doi: 10.1038/s41467-020-17467-z

Jochems, F. et al. The cancer SENESCopedia: a delineation of cancer cell senescence. Cell Rep. 36, 109441 (2021).

pubmed: 34320349 pmcid: 8333195 doi: 10.1016/j.celrep.2021.109441

Cherry, C. et al. Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies. Geroscience 45, 2559–2587 (2023).

pubmed: 37079217 pmcid: 10651581 doi: 10.1007/s11357-023-00785-7

Wallis, R. et al. Senescence-associated morphological profiles (SAMPs): an image-based phenotypic profiling method for evaluating the inter and intra model heterogeneity of senescence. Aging 14, 4220–4246 (2022).

pubmed: 35580013 pmcid: 9186762 doi: 10.18632/aging.204072

Kusumoto, D. et al. Anti-senescent drug screening by deep learning-based morphology senescence scoring. Nat. Commun. 12, 257 (2021).

pubmed: 33431893 pmcid: 7801636 doi: 10.1038/s41467-020-20213-0

Heckenbach, I. et al. Nuclear morphology is a deep learning biomarker of cellular senescence. Nat. Aging 2, 742–755 (2022).

pubmed: 37118134 pmcid: 10154217 doi: 10.1038/s43587-022-00263-3

Basisty, N. et al. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biol. 18, e3000599 (2020).

pubmed: 31945054 pmcid: 6964821 doi: 10.1371/journal.pbio.3000599

Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008).

pubmed: 18555777 doi: 10.1016/j.cell.2008.03.038

Kuilman, T. et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133, 1019–1031 (2008).

pubmed: 18555778 doi: 10.1016/j.cell.2008.03.039

Basisty, N., Kale, A., Patel, S., Campisi, J. & Schilling, B. The power of proteomics to monitor senescence-associated secretory phenotypes and beyond: toward clinical applications. Expert. Rev. Proteom. 17, 297–308 (2020).

doi: 10.1080/14789450.2020.1766976

Tanaka, T. et al. Plasma proteomic biomarker signature of age predicts health and life span. eLife 9, e61073 (2020).

pubmed: 33210602 pmcid: 7723412 doi: 10.7554/eLife.61073

Fielding, R. A. et al. Associations between biomarkers of cellular senescence and physical function in humans: observations from the lifestyle interventions for elders (LIFE) study. Geroscience 44, 2757–2770 (2022).

pubmed: 36367600 pmcid: 9768064 doi: 10.1007/s11357-022-00685-2

Tanaka, T. et al. Plasma proteomic signature of age in healthy humans. Aging Cell 17, e12799 (2018).

pubmed: 29992704 pmcid: 6156492 doi: 10.1111/acel.12799

Shin, J. W., Lee, E., Han, S., Choe, S. A. & Jeon, O. H. Plasma proteomic signature of cellular senescence and markers of biological aging among postmenopausal women. Rejuvenation Res. 25, 141–148 (2022).

pubmed: 35583231 doi: 10.1089/rej.2022.0024

Wiley, C. D. et al. Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis. Cell Metab. 33, 1124–1136.e5 (2021).

pubmed: 33811820 pmcid: 8501892 doi: 10.1016/j.cmet.2021.03.008

Wiley, C. D. et al. Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis. JCI Insight 4, e130056 (2019).

pubmed: 31687975 pmcid: 6975274 doi: 10.1172/jci.insight.130056

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.e6 (2019).

pubmed: 31242426 pmcid: 6613042 doi: 10.1016/j.celrep.2019.05.095

Covre, L. P., De Maeyer, R. P. H., Gomes, D. C. O. & Akbar, A. N. The role of senescent T cells in immunopathology. Aging Cell 19, e13272 (2020).

pubmed: 33166035 pmcid: 7744956 doi: 10.1111/acel.13272

Frasca, D. Senescent B cells in aging and age-related diseases: their role in the regulation of antibody responses. Exp. Gerontol. 107, 55–58 (2018).

pubmed: 28687479 doi: 10.1016/j.exger.2017.07.002

Ong, S. M. et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 9, 266 (2018).

pubmed: 29449647 pmcid: 5833376 doi: 10.1038/s41419-018-0327-1

Walker, K. A., Basisty, N., Wilson, D. M. III & Ferrucci, L. Connecting aging biology and inflammation in the omics era. J. Clin. Invest 132, e158448 (2022).

pubmed: 35838044 pmcid: 9282936 doi: 10.1172/JCI158448

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).

pubmed: 31542391 pmcid: 6796530 doi: 10.1016/j.ebiom.2019.08.069

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).

pubmed: 30616998 pmcid: 6412088 doi: 10.1016/j.ebiom.2018.12.052

Wiley, C. D. et al. SILAC analysis reveals increased secretion of hemostasis-related factors by senescent cells. Cell Rep. 28, 3329–3337.e5 (2019).

pubmed: 31553904 pmcid: 6907691 doi: 10.1016/j.celrep.2019.08.049

Gurkar, A. U. et al. Spatial mapping of cellular senescence: emerging challenges and opportunities. Nat. Aging 3, 776–790 (2023).

pubmed: 37400722 pmcid: 10505496 doi: 10.1038/s43587-023-00446-6

Kramer, B. A., Del Castillo, J. S., Pelkmans, L. & Gut, G. Iterative indirect immunofluorescence imaging (4i) on adherent cells and tissue sections. Bio Protoc. 13, e4712 (2023).

pubmed: 37449033 pmcid: 10336569

Black, S. et al. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat. Protoc. 16, 3802–3835 (2021).

pubmed: 34215862 pmcid: 8647621 doi: 10.1038/s41596-021-00556-8

Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015).

pubmed: 25858977 pmcid: 4662681 doi: 10.1126/science.aaa6090

SenNet recommendations for detecting senescent cells in different tissues.

Journal

Informations de publication

Résumé

Identifiants

Types de publication

Langues

Sous-ensembles de citation

Informations de copyright

Références

Auteurs

Classifications MeSH