A Senescence-Centric View of Aging: Implications for Longevity and Disease
Open accessAbstract
Cellular senescence is a state of stable cell cycle arrest associated with macromolecular alterations and secretion of proinflammatory cytokines and molecules. From their initial discovery in the 1960s, senescent cells have been hypothesized as potential contributors to the age-associated loss of regenerative potential. Here, we discuss recent evidence that implicates cellular senescence as a central regulatory mechanism of the aging process. We provide a comprehensive overview of age-associated pathologies in which cellular senescence has been implicated. We describe mechanisms by which senescent cells drive aging and diseases, and we discuss updates on exploiting these mechanisms as therapeutic targets. Finally, we critically analyze the use of senotherapeutics and their translation to the clinic, highlighting limitations and suggesting ideas for future applications and developments.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Senescent cells contribute to the initiation and progression of various aging-related chronic diseases.
“and contribute to the initiation and progression of various aging-related chronic diseases.9,10,11”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [11]
Natural accumulation of senescent cells in mammals during ageing contributes to development of various age-associated diseases.
“The natural accumulation of senescent cells in mammals during ageing contributes to the development of various age‐associated diseases (Baker et al, 2016; Calcinotto et al, 2019; Borghesan et al, 2020).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Borghesan et al, 2020
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Epidemiology of Parkinson's disease
de Lau, L. M., & Breteler, M. M. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70471-9 · Cited by 4,110 · cited 1× · see citing works
“The prevalence of Parkinson’s disease (PD), the secondmost common neurodegenerative disorder, increases with advanced age [88].”
BackgroundCruz-Jentoft, A. J., & Sayer, A. A. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31138-9 · Cited by 3,905 · see citing works
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225 · cited 1× · see citing works
“Other common features observed in senescent cells are profound changes in (epi)genetic landscape and gene expression, persistent macromolecular damage, and aberrant metabolism and activation of a hypersecretory phenotype [1,2].”
BackgroundSelf-citationNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,891 · see citing works
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
Self-citationThe Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,562 · cited 9× · see citing works
“In addition to ameliorating several metabolic parameters, treatment with D+Q in obese mice also reduced diabetic nephropathy, leading to an improvement in kidney proteinuria and glomerulopathy [96].”
BackgroundInfluentialSenolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · see citing works
A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278 · cited 1× · see citing works
“Thus, immunosenescence contributes to altered inflammatory response and impaired stem cell function [3,9], which might be explained by incipient senescence activation, sustained secretion of SASP factors and senescence-induced inflammasome activation [29].”
BackgroundPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045 · see citing works
Self-citationClearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · see citing works
Self-citationTRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709 · see citing works
Cellular senescence mediates fibrotic pulmonary disease
Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., Oberg, A. L., Birch, J., Salmonowicz, H., Zhu, Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms14532 · Cited by 1,613 · cited 2× · see citing works
“Navitoclax (ABT-263) Senolytic Bcl-2/Bcl-x family AD, cancer; stem cell rejuvenation, lung fibrosis, atherosclerosis [77,99,114,125,126]”
BackgroundJeon, O. H., Kim, C., Laberge, R.-M., Demaria, M., Rathod, S., Vasserot, A. P., Chung, J. W., Kim, D. H., Poon, Y., David, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4324 · Cited by 1,515 · cited 3× · see citing works
“In OA human chondrocytes, UBX0101 treatment improved the synthesis of ECM proteins, promoting a proregenerative environment [36], while another senolytic compound, Fenofibrate (a PPARα agonist), reduced proteoglycan loss in IL-1β-treated human cartilage explants [41].”
BackgroundSelf-citationBaar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454 · see citing works
Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.069 · Cited by 1,383 · cited 2× · see citing works
“In a different Phase I study (NCT02848131), a single 3-day course of D+Q in diabetic patients with CKD was also found to be safe and resulted in significant decreases in senescent cells in skin and adipose tissue, and a decrease of circulating SASP factors (IL-1α, IL-2, IL-6, IL-9, MMP-2, MMP-9, and MMP-12) [113].”
BackgroundAutophagy maintains stemness by preventing senescence
García-Prat, L., Martínez-Vicente, M., Perdiguero, E., Ortet, L., Rodríguez-Ubreva, J., Rebollo, E., Ruiz-Bonilla, V., Gutarra, S., Ballestar, E., Serrano, A. L., et al. (2016) · Nature · doi:10.1038/nature16187 · Cited by 1,355 · see citing works
A proteomic atlas of senescence-associated secretomes for aging biomarker development
Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., Ferrucci, L., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000599 · Cited by 1,348 · see citing works
Cellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338 · see citing works
Self-citationClearance of senescent glial cells prevents tau-dependent pathology and cognitive decline
Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018) · Nature · doi:10.1038/s41586-018-0543-y · Cited by 1,289 · see citing works
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.011 · Cited by 1,275 · cited 2× · see citing works
“Increases in AMP:ATP and ADP:ATP ratios also contribute to functional decline of sirtuin proteins and poly-ADP ribose polymerase (PARP), which are important modulators of SASP and NF-κB [15,16].”
BackgroundCellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270 · see citing works
Self-citationSenolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.12.052 · Cited by 1,261 · cited 2× · see citing works
“In a single-arm, open-label pilot study without placebo (NCT02874989), repeated D+Q treatment of IPF patients was safe, with only mild to moderate reversible adverse events, and resulted in significant improvement of functional measures, such as 6-min walking distance, 4-m gait speed, chair-stands, and Short Physical…”
BackgroundSenescent intimal foam cells are deleterious at all stages of atherosclerosis
Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016) · Science · doi:10.1126/science.aaf6659 · Cited by 1,195 · see citing works
Targeting cellular senescence prevents age-related bone loss in mice
Farr, J. N., Xu, M., Weivoda, M. M., Monroe, D. G., Fraser, D. G., Onken, J. L., Negley, B. A., Sfeir, J. G., Ogrodnik, M. B., Hachfeld, C. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4385 · Cited by 1,182 · see citing works
Senescence-associated reprogramming promotes cancer stemness
Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., Dörr, J. R., Dimitrova, L., Lenze, D., Monteiro Barbosa, I. A., et al. (2018) · Nature · doi:10.1038/nature25167 · Cited by 1,131 · see citing works
Lepper, C., Partridge, T. A., & Fan, C.-M. (2011) · Development · doi:10.1242/dev.067595 · Cited by 1,105 · see citing works
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104 · see citing works
Autophagy mediates the mitotic senescence transition
Young, A. R. J., Narita, M., Ferreira, M., Kirschner, K., Sadaie, M., Darot, J. F. J., Tavaré, S., Arakawa, S., Shimizu, S., Watt, F. M., et al. (2009) · Genes & Development · doi:10.1101/gad.519709 · Cited by 1,078 · see citing works
Endothelial Cell Senescence in Human Atherosclerosis: Role of Telomere in Endothelial Dysfunction
Minamino, T., Miyauchi, H., Yoshida, T., Ishida, Y., Yoshida, H., & Komuro, I. (2002) · Circulation · doi:10.1161/01.cir.0000013836.85741.17 · Cited by 1,061 · see citing works
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032 · see citing works
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.015 · Cited by 1,032 · see citing works
Feedback between p21 and reactive oxygen production is necessary for cell senescence
Passos, J. F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C. J., Miwa, S., Olijslagers, S., Hallinan, J., Wipat, A., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.5 · Cited by 1,019 · cited 2× · see citing works
“Like telomeres, dysfunctional mitochondria lead to senescence [14].”
BackgroundGeriatric muscle stem cells switch reversible quiescence into senescence
Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A. L., et al. (2014) · Nature · doi:10.1038/nature13013 · Cited by 1,010 · see citing works
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982 · see citing works
Self-citationZhang, P., Kishimoto, Y., Grammatikakis, I., Gottimukkala, K., Cutler, R. G., Zhang, S., Abdelmohsen, K., Bohr, V. A., Misra Sen, J., Gorospe, M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0372-9 · Cited by 977 · see citing works
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972 · cited 3× · see citing works
“The SASP is a highly heterogeneous program whose composition depends on various intrinsic and extrinsic factors [4,5].”
BackgroundSelf-citationWang (2012) · doi:10.1161/circresaha.111.261388 · Cited by 957 · see citing works
Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration
Sambasivan, R., Yao, R., Kissenpfennig, A., Van Wittenberghe, L., Paldi, A., Gayraud-Morel, B., Guenou, H., Malissen, B., Tajbakhsh, S., & Galy, A. (2011) · Development · doi:10.1242/dev.067587 · Cited by 939 · see citing works
Xu, M., Tchkonia, T., Ding, H., Ogrodnik, M., Lubbers, E. R., Pirtskhalava, T., White, T. A., Johnson, K. O., Stout, M. B., Mezera, V., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515386112 · Cited by 915 · cited 3× · see citing works
“For example, the FDA-approved Janus kinase (JAK 1/2) and signal transducer and activator of transcription protein 3 (STAT3) inhibitor, ruxolitinib, shown to be a SASP inhibitor [53], reduce bone resorption while promoting new bone formation [47].”
BackgroundMitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796 · see citing works
Benefits of Metformin in Attenuating the Hallmarks of Aging
Kulkarni, A. S., Gubbi, S., & Barzilai, N. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.001 · Cited by 766 · see citing works
Zhu, Y., Doornebal, E. J., Pirtskhalava, T., Giorgadze, N., Wentworth, M., Fuhrmann-Stroissnigg, H., Niedernhofer, L. J., Robbins, P. D., Tchkonia, T., & Kirkland, J. L. (2017) · Aging · doi:10.18632/aging.101202 · Cited by 757 · see citing works
Identification of HSP90 inhibitors as a novel class of senolytics
Fuhrmann-Stroissnigg, H., Ling, Y. Y., Zhao, J., McGowan, S. J., Zhu, Y., Brooks, R. W., Grassi, D., Gregg, S. Q., Stripay, J. L., Dorronsoro, A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00314-z · Cited by 701 · see citing works
Targeting senescent cells alleviates obesity-induced metabolic dysfunction
Palmer, A. K., Xu, M., Zhu, Y., Pirtskhalava, T., Weivoda, M. M., Hachfeld, C. M., Prata, L. G., van Dijk, T. H., Verkade, E., Casaclang‐Verzosa, G., et al. (2019) · Aging Cell · doi:10.1111/acel.12950 · Cited by 658 · see citing works
Self-citationSecretion of vascular endothelial growth factor by primary human fibroblasts at senescence
Coppé, J.-P., Kauser, K., Campisi, J., & Beauséjour, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603307200 · Cited by 604 · see citing works
PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1
Pridgeon, J. W., Olzmann, J. A., Chin, L.-S., & Li, L. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050172 · Cited by 596 · see citing works
Tau protein aggregation is associated with cellular senescence in the brain
Musi, N., Valentine, J. M., Sickora, K. R., Baeuerle, E., Thompson, C. S., Shen, Q., & Orr, M. E. (2018) · Aging Cell · doi:10.1111/acel.12840 · Cited by 595 · see citing works
Astrocyte Senescence as a Component of Alzheimer’s Disease
Bhat, R., Crowe, E. P., Bitto, A., Moh, M., Katsetos, C. D., Garcia, F. U., Johnson, F. B., Trojanowski, J. Q., Sell, C., & Torres, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045069 · Cited by 586 · see citing works
Impaired immune surveillance accelerates accumulation of senescent cells and aging
Ovadya, Y., Landsberger, T., Leins, H., Vadai, E., Gal, H., Biran, A., Yosef, R., Sagiv, A., Agrawal, A., Shapira, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07825-3 · Cited by 578 · see citing works
T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
Desdín-Micó, G., Soto-Heredero, G., Aranda, J. F., Oller, J., Carrasco, E., Gabandé-Rodríguez, E., Blanco, E. M., Alfranca, A., Cussó, L., Desco, M., et al. (2020) · Science · doi:10.1126/science.aax0860 · Cited by 572 · see citing works
Identification of senescent cells in the bone microenvironment
Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2892 · Cited by 562 · see citing works
Osteoarthritis year in review 2019: epidemiology and therapy
Kloppenburg, M., & Berenbaum, F. (2020) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2020.01.002 · Cited by 544 · see citing works
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy
Dörr, J. R., Yu, Y., Milanovic, M., Beuster, G., Zasada, C., Däbritz, J. H. M., Lisec, J., Lenze, D., Gerhardt, A., Schleicher, K., et al. (2013) · Nature · doi:10.1038/nature12437 · Cited by 541 · see citing works
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Ogrodnik, M., Zhu, Y., Langhi, L. G. P., Tchkonia, T., Krüger, P., Fielder, E., Victorelli, S., Ruswhandi, R. A., Giorgadze, N., Pirtskhalava, T., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.008 · Cited by 536 · see citing works
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · cited 3× · see citing works
“Importantly, ablation of senescent cells in aged mice using the INK-ATTAC mouse model or senolytics (D+Q or navitoclax) resulted in a decrease of fibrosis and hypertrophy and increase in smaller proliferating cardiomyocytes, suggesting that removal of senescent cardiomyocytes and/or cardiac progenitor cells could resc…”
BackgroundMethodChinta, S. J., Woods, G., Demaria, M., Rane, A., Zou, Y., McQuade, A., Rajagopalan, S., Limbad, C., Madden, D. T., Campisi, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.092 · Cited by 530 · cited 1× · see citing works
“Neurotoxin-induced PD has been shown to be accompanied by accumulation of senescent cells, while the elimination of senescent astrocytes by the use of a transgene protects against neuropathology [90].”
BackgroundSelf-citationA Clinical Frailty Index in Aging Mice: Comparisons With Frailty Index Data in Humans
Whitehead, J. C., Hildebrand, B. A., Sun, M., Rockwood, M. R. H., Rose, R. A., Rockwood, K. J., & Howlett, S. E. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt136 · Cited by 514 · see citing works
Senescent Cells in Cancer Therapy: Friends or Foes?
Wang, B., Kohli, J., & Demaria, M. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.05.004 · Cited by 508 · see citing works
Self-citationReciprocal regulation of p53 and malic enzymes modulates metabolism and senescence
Jiang, P., Du, W., Mancuso, A., Wellen, K. E., & Yang, X. (2013) · Nature · doi:10.1038/nature11776 · Cited by 491 · see citing works
Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
Carlson, M. E., Hsu, M., & Conboy, I. M. (2008) · Nature · doi:10.1038/nature07034 · Cited by 483 · see citing works
Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes
Aguayo-Mazzucato, C., Andle, J., Lee, T. B., Midha, A., Talemal, L., Chipashvili, V., Hollister-Lock, J., van Deursen, J., Weir, G., & Bonner-Weir, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.006 · Cited by 469 · see citing works
NF-κB inhibition delays DNA damage–induced senescence and aging in mice
Tilstra, J. S., Robinson, A. R., Wang, J., Gregg, S. Q., Clauson, C. L., Reay, D. P., Nasto, L. A., St Croix, C. M., Usas, A., Vo, N., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45785 · Cited by 462 · see citing works
Inducing and exploiting vulnerabilities for the treatment of liver cancer
Wang, C., Vegna, S., Jin, H., Benedict, B., Lieftink, C., Ramirez, C., de Oliveira, R. L., Morris, B., Gadiot, J., Wang, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1607-3 · Cited by 427 · see citing works
Cellular senescence: a link between cancer and age-related degenerative disease?
Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.09.001 · Cited by 421 · see citing works
The age factor in Alzheimer’s disease
Guerreiro, R., & Bras, J. (2015) · Genome Medicine · doi:10.1186/s13073-015-0232-5 · Cited by 415 · see citing works
Lehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H. N., Ota, C., Costa, R., Schiller, H. B., Lindner, M., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.02367-2016 · Cited by 403 · cited 1× · see citing works
“In IPF models, clearance of senescent epithelial cells in INK-ATTACmice or by the senolytics D+Q, improves overall pulmonary function and elastance [77] as seen also by reductions in ECM deposition and the associated profibrotic SASP [78].”
BackgroundCai, Y., Zhou, H., Zhu, Y., Sun, Q., Ji, Y., Xue, A., Wang, Y., Chen, W., Yu, X., Wang, L., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0314-9 · Cited by 397 · see citing works
The role of chondrocyte senescence in osteoarthritis
Price, J. S., Waters, J. G., Darrah, C., Pennington, C., Edwards, D. R., Donell, S. T., & Clark, I. M. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00008.x · Cited by 386 · see citing works
Identification and characterization of Cardiac Glycosides as senolytic compounds
Triana-Martínez, F., Picallos-Rabina, P., Da Silva-Álvarez, S., Pietrocola, F., Llanos, S., Rodilla, V., Soprano, E., Pedrosa, P., Ferreirós, A., Barradas, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12888-x · Cited by 384 · see citing works
(2000) · PubMed · Cited by 371 · see citing works
Thymic involution and rising disease incidence with age
Palmer, S., Albergante, L., Blackburn, C. C., & Newman, T. J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714478115 · Cited by 364 · see citing works
Cardiac glycosides are broad-spectrum senolytics
Guerrero, A., Herranz, N., Sun, B., Wagner, V., Gallage, S., Guiho, R., Wolter, K., Pombo, J., Irvine, E. E., Innes, A. J., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0122-z · Cited by 359 · see citing works
Transcriptome signature of cellular senescence
Casella, G., Munk, R., Kim, K. M., Piao, Y., De, S., Abdelmohsen, K., & Gorospe, M. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz555 · Cited by 359 · see citing works
Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes
Thompson, P. J., Shah, A., Ntranos, V., Van Gool, F., Atkinson, M., & Bhushan, A. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.021 · Cited by 353 · see citing works
Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice
Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., Curran, G. L., Ogrodnik, M., Jurk, D., Johnson, K. O., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw154 · Cited by 352 · see citing works
Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability
Wang, J., Uryga, A. K., Reinhold, J., Figg, N., Baker, L., Finigan, A., Gray, K., Kumar, S., Clarke, M., & Bennett, M. (2015) · Circulation · doi:10.1161/circulationaha.115.016457 · Cited by 349 · see citing works
NKG2D ligands mediate immunosurveillance of senescent cells
Sagiv, A., Burton, D. G. A., Moshayev, Z., Vadai, E., Wensveen, F., Ben-Dor, S., Golani, O., Polic, B., & Krizhanovsky, V. (2016) · Aging · doi:10.18632/aging.100897 · Cited by 345 · see citing works
Role of oxidatively induced DNA lesions in human pathogenesis
Sedelnikova, O. A., Redon, C. E., Dickey, J. S., Nakamura, A., Georgakilas, A. G., & Bonner, W. M. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2009.12.005 · Cited by 339 · see citing works
Hepatocyte senescence predicts progression in non-alcohol-related fatty liver disease
Aravinthan, A., Scarpini, C., Tachtatzis, P., Verma, S., Penrhyn-Lowe, S., Harvey, R., Davies, S. E., Allison, M., Coleman, N., & Alexander, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2012.10.031 · Cited by 326 · see citing works
Aged-senescent cells contribute to impaired heart regeneration
Lewis‐McDougall, F. C., Ruchaya, P. J., Domenjo‐Vila, E., Shin Teoh, T., Prata, L., Cottle, B. J., Clark, J. E., Punjabi, P. P., Awad, W., Torella, D., et al. (2019) · Aging Cell · doi:10.1111/acel.12931 · Cited by 317 · see citing works
Chen, D., Xia, D., Pan, Z., Xu, D., Zhou, Y., Wu, Y., Cai, N., Tang, Q., Wang, C., Yan, M., et al. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.334 · Cited by 314 · see citing works
Metformin limits osteoarthritis development and progression through activation of AMPK signalling
Li, J., Zhang, B., Liu, W., Lu, K., Pan, H., Wang, T., Oh, C., Yi, D., Huang, J. H., Zhao, L., et al. (2020) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-216713 · Cited by 305 · see citing works
González‐Gualda, E., Pàez‐Ribes, M., Lozano‐Torres, B., Macias, D., Wilson, J. R., González‐López, C., Ou, H., Mirón‐Barroso, S., Zhang, Z., Lérida‐Viso, A., et al. (2020) · Aging Cell · doi:10.1111/acel.13142 · Cited by 303 · see citing works
He, Y., Zhang, X., Chang, J., Kim, H.-N., Zhang, P., Wang, Y., Khan, S., Liu, X., Zhang, X., Lv, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15838-0 · Cited by 280 · see citing works
Discovery of piperlongumine as a potential novel lead for the development of senolytic agents
Wang, Y., Chang, J., Liu, X., Zhang, X., Zhang, S., Zhang, X., Zhou, D., & Zheng, G. (2016) · Aging · doi:10.18632/aging.101100 · Cited by 274 · see citing works
Bird, T. G., Müller, M., Boulter, L., Vincent, D. F., Ridgway, R. A., Lopez-Guadamillas, E., Lu, W.-Y., Jamieson, T., Govaere, O., Campbell, A. D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan1230 · Cited by 261 · see citing works
Tumor cell escape from therapy-induced senescence as a model of disease recurrence after dormancy.
Saleh, T., Tyutyunyk-Massey, L., & Gewirtz, D. A. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3437 · Cited by 259 · see citing works
ANTAGONISTIC PLEIOTROPY, MORTALITY SOURCE INTERACTIONS, AND THE EVOLUTIONARY THEORY OF SENESCENCE
Williams, P. D., & Day, T. (2003) · Evolution · doi:10.1111/j.0014-3820.2003.tb00356.x · Cited by 258 · see citing works
Jin Bing, P. A. N., Li, D., Xu, Y., Zhang, J., Wang, Y., Chen, M., Lin, S., Huang, L., Chung, E. J., Citrin, D. E., et al. (2017) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2017.02.216 · Cited by 244 · see citing works
Wiley, C. D., Flynn, J. M., Morrissey, C., Lebofsky, R., Shuga, J., Dong, X., Unger, M. A., Vijg, J., Melov, S., & Campisi, J. (2017) · Aging Cell · doi:10.1111/acel.12632 · Cited by 234 · cited 1× · see citing works
“There is increasing evidence that a small fraction of senescent cells in a population is the main source of SASP factors [118] and inflammatory response.”
BackgroundTuomisto, K., Jousilahti, P., Sundvall, J., Pajunen, P., & Salomaa, V. V. (2006) · Thrombosis and Haemostasis · doi:10.1160/th05-08-0571 · Cited by 231 · see citing works
Fleury, H., Malaquin, N., Tu, V., Gilbert, S., Martinez, A., Olivier, M.-A., Sauriol, S. A., Communal, L., Leclerc-Desaulniers, K., Carmona, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10460-1 · Cited by 228 · see citing works
Chung, C. L., Lawrence, I., Hoffman, M. L., Elgindi, D., Nadhan, K. S., Potnis, M., Jin, A., Sershon, C., Binnebose, R., Lorenzini, A., et al. (2019) · GeroScience · doi:10.1007/s11357-019-00113-y · Cited by 226 · see citing works
Immunosenescence of Human Natural Killer Cells
Gayoso, I., Sánchez-Correa, B., Campos, C., Alonso, C., Pera, A., Casado, J. G., Morgado, S., Tarazona, R., & Solana, R. (2011) · Journal of Innate Immunity · doi:10.1159/000328005 · Cited by 210 · see citing works
A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells
Wakita, M., Takahashi, A., Sano, O., Loo, T. M., Imai, Y., Narukawa, M., Iwata, H., Matsudaira, T., Kawamoto, S., Ohtani, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15719-6 · Cited by 206 · see citing works
Saito, Y., Chikenji, T. S., Matsumura, T., Nakano, M., & Fujimiya, M. (2020) · Nature Communications · doi:10.1038/s41467-020-14734-x · Cited by 196 · see citing works
Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation
Deschênes-Simard, X., Gaumont-Leclerc, M.-F., Bourdeau, V., Lessard, F., Moiseeva, O., Forest, V., Igelmann, S., Mallette, F. A., Saba-El-Leil, M. K., Meloche, S., et al. (2013) · Genes & Development · doi:10.1101/gad.203984.112 · Cited by 194 · see citing works
Takayama, K., Kawakami, Y., Kobayashi, M., Greco, N., Cummins, J. H., Matsushita, T., Kuroda, R., Kurosaka, M., Fu, F. H., & Huard, J. (2014) · Arthritis Research & Therapy · doi:10.1186/s13075-014-0482-4 · Cited by 191 · see citing works
Chemical screening identifies ATM as a target for alleviating senescence
Kang, H. T., Park, J. T., Choi, K., Kim, Y., Choi, H. J. C., Jung, C. W., Lee, Y.-S., & Park, S. C. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2342 · Cited by 184 · see citing works
Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons
Riessland, M., Kolisnyk, B., Kim, T. W., Cheng, J., Ni, J., Pearson, J. A., Park, E. J., Dam, K., Acehan, D., Ramos-Espiritu, L. S., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.08.013 · Cited by 180 · see citing works
Cellular Senescence Limits Regenerative Capacity and Allograft Survival
Braun, H., Schmidt, B. M. W., Raiss, M., Baisantry, A., Mircea-Constantin, D., Wang, S., Groß, M.-L., Serrano, M., Schmitt, R., & Melk, A. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011100967 · Cited by 179 · see citing works
Lung fibroblasts from patients with emphysema show markers of senescence in vitro
Müller, K., Welker, L., Paasch, K., Feindt, B., Erpenbeck, V., Hohlfeld, J. M., Krug, N., Nakashima, M., Branscheid, D., MAGNUSSEN, H., et al. (2006) · Respiratory Research · doi:10.1186/1465-9921-7-32 · Cited by 173 · see citing works
Rapamycin and Alzheimer’s disease: Time for a clinical trial?
Kaeberlein, M. R., & Galván, V. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aar4289 · Cited by 170 · see citing works
Patil, P. R., Dong, Q. D., Wang, D., Chang, J., Wiley, C. D., Demaria, M., Lee, J., Kang, J. D., Niedernhofer, L. J., Robbins, P. D., et al. (2019) · Aging Cell · doi:10.1111/acel.12927 · Cited by 169 · see citing works
Self-citationElimination of p19ARF-expressing cells enhances pulmonary function in mice
Hashimoto, M., Asai, A., Kawagishi, H., Mikawa, R., Iwashita, Y., Kanayama, K., Sugimoto, K., Sato, T., Maruyama, M., & Sugimoto, M. (2016) · JCI Insight · doi:10.1172/jci.insight.87732 · Cited by 162 · see citing works
Paracrine cellular senescence exacerbates biliary injury and impairs regeneration
Ferreira-Gonzalez, S., Lu, W.-Y., Raven, A., Dwyer, B., Man, T. Y., O’Duibhir, E., Lewis, P. J. S., Campana, L., Kendall, T. J., Bird, T. G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03299-5 · Cited by 161 · see citing works
Zheng, W., Feng, Z., You, S., Zhang, H., Tao, Z., Wang, Q., Chen, H., & Wu, Y. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.02.009 · Cited by 160 · see citing works
Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy
Nogueira-Recalde, U., Lorenzo-Gómez, I., Blanco, F. J., Loza, M. I., Grassi, D., Shirinsky, V., Shirinsky, I., Lotz, M., Robbins, P. D., Domínguez, E., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.049 · Cited by 155 · see citing works
Geng, Q., Gao, H., Yang, R., Guo, K., & Miao, D. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.25783 · Cited by 152 · see citing works
Kang, D., Shin, J., Cho, Y., Kim, H.-S., Gu, Y.-R., Kim, H., You, K. T., Chang, M. J., Chang, C. B., Kang, S., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aar6659 · Cited by 148 · see citing works
Geroconversion: irreversible step to cellular senescence
Blagosklonny, M. V. (2014) · Cell Cycle · doi:10.4161/15384101.2014.985507 · Cited by 140 · see citing works
Targeted Reduction of Senescent Cell Burden Alleviates Focal Radiotherapy-Related Bone Loss
Chandra, A., Lagnado, A. B., Farr, J. N., Monroe, D. G., Park, S., Hachfeld, C., Tchkonia, T., Kirkland, J. L., Khosla, S., Passos, J. F., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3978 · Cited by 138 · see citing works
Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease
Xia, M., Xie, X., Ding, J., Du, R., & Hu, G. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01791-8 · Cited by 138 · see citing works
Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro
Cherif, H., Bisson, D. G., Jarzem, P. F., Weber, M. H., Ouellet, J. A., & Haglund, L. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8040433 · Cited by 137 · see citing works
A Role for Immature Myeloid Cells in Immune Senescence
Enioutina, E. Y., Bareyan, D., & Daynes, R. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002987 · Cited by 130 · see citing works
Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes
Eckhardt, B. A., Rowsey, J. L., Thicke, B. S., Fraser, D. G., O’Grady, K. L., Bondar, O. P., Hines, J. M., Singh, R. J., Thoreson, A. R., Rakshit, K., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.135236 · Cited by 130 · see citing works
Therapy-Induced Senescence Drives Bone Loss
Yao, Z., Murali, B., Ren, Q., Luo, X., Faget, D. V., Cole, T., Ricci, B., Thotala, D., Monahan, J., van Deursen, J. M., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2348 · Cited by 129 · see citing works
Rapamycin protects chondrocytes against IL-18-induced apoptosis and ameliorates rat osteoarthritis
Bao, J., Chen, Z., Xu, L., Wu, L., & Xiong, Y. (2020) · Aging · doi:10.18632/aging.102937 · Cited by 126 · see citing works
Metformin; an old antidiabetic drug with new potentials in bone disorders
Bahrambeigi, S., Yousefi, B., Rahimi, M., & Shafiei‐Irannejad, V. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.032 · Cited by 122 · see citing works
Chkhotua, A. B., Gabusi, E., Altimari, A., D’Errico, A., Yakubovich, M., Vienken, J., Stefoni, S., Chieco, P., Yussim, A., & Grigioni, W. F. (2003) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(03)00363-9 · Cited by 120 · cited 1× · see citing works
“Increased senescence of tubular kidney cells has been associated with CKD as well as chronic allograft nephropathy in both mouse models and humans [79].”
BackgroundSatellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H
Kudryashova, E., Kramerova, I., & Spencer, M. J. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59581 · Cited by 119 · see citing works
Weiss, T., Arnesen, H., & Seljeflot, I. (2013) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2013.01.019 · Cited by 109 · see citing works
Bigot, A., Klein, A., Gasnier, E., Jacquemin, V., Ravassard, P., Butler-Browne, G., Mouly, V., & Furling, D. (2009) · American Journal of Pathology · doi:10.2353/ajpath.2009.080560 · Cited by 106 · see citing works
Ritschka, B., Knauer-Meyer, T., Gonçalves, D. S., Mas, A., Plassat, J.-L., Durik, M., Jacobs, H., Pedone, E., Di Vicino, U., Cosma, M. P., et al. (2020) · Genes & Development · doi:10.1101/gad.332643.119 · Cited by 105 · see citing works
Wei, Z., Chen, X.-C., Song, Y., Pan, X.-D., Dai, X.-M., Zhang, J., Cui, X.-L., Wu, X.-L., & Zhu, Y.-G. (2016) · Chinese Medical Journal · doi:10.4103/0366-6999.186646 · Cited by 89 · see citing works
Gao, S., Zeng, C., Li, L., Luo, W., Zhang, F., Tian, J., Cheng, C., Tu, M., Xiong, Y., Jiang, W. H., et al. (2013) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.12096 · Cited by 87 · see citing works
Wolstein, J. M., Lee, D. H., Michaud, J., Buot, V., Stefanchik, B., & Plotkin, M. D. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00378.2010 · Cited by 83 · see citing works
Transcriptome signature of cellular senescence
Casella, G., Munk, R., Kim, K. M., Piao, Y., De, S., Abdelmohsen, K., & Gorospe, M. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz879 · Cited by 83 · see citing works
Frailty index as a biomarker of lifespan and healthspan: Focus on pharmacological interventions
Palliyaguru, D. L., Moats, J. M., Germanio, C. D., Bernier, M., & de Cabo, R. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.03.005 · Cited by 72 · see citing works
Aging Fits the Disease Criteria of the International Classification of Diseases
Khaltourina, D. A., Matveyev, Y., Alekseev, A., Cortese, F., & Ioviţă, A. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111230 · Cited by 71 · see citing works
Rocha, L. R., Nguyen Huu, V. A., Palomino La Torre, C., Xu, Q., Jabari, M., Krawczyk, M., Weinreb, R. N., & Skowronska‐Krawczyk, D. (2020) · Aging Cell · doi:10.1111/acel.13089 · Cited by 68 · see citing works
Singh, M., Jensen, M. D., Lerman, A., Kushwaha, S. S., Rihal, C., Gersh, B. J., Behfar, A., Tchkonia, T., Thomas, R. J., Lennon, R. J., et al. (2016) · The Journal of Frailty & Aging · doi:10.14283/jfa.2016.112 · Cited by 62 · see citing works
Martin-Ruiz, C. M., Williams‐Gray, C. H., Yarnall, A. J., Boucher, J. J., Lawson, R. A., Wijeyekoon, R., Barker, R. A., Kolenda, C., Parker, C., Burn, D. J., et al. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191724 · Cited by 61 · see citing works
Gayle, S. S., Sahni, J. M., Webb, B. M., Weber-Bonk, K. L., Shively, M. S., Spina, R., Bar, E. E., Summers, M. K., & Keri, R. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004712 · Cited by 60 · see citing works
Fali, T., Fabre-Mersseman, V., Yamamoto, T., Bayard, C., Papagno, L., Fastenackels, S., Zoorab, R., Koup, R. A., Boddaert, J., Sauce, D., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.95319 · Cited by 55 · see citing works
Cao, X., Luo, P., Huang, J., Liang, C., He, J., Wang, Z., Shan, D., Peng, C., & Song, W. C. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1193-1 · Cited by 53 · see citing works
Espinoza, S. E., Musi, N., Wang, C.-P., Michalek, J. E., Orsak, B., Romo, T. Q., Powers, B., Conde, A., Moris, M., Bair‐Kelps, D., et al. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz078 · Cited by 52 · see citing works
Barbouti, A., Evangelou, K., Pateras, I. S., Papoudou-Bai, A., Patereli, A., Stefanaki, K., Rontogianni, D., Muñoz-Espín, D., Kanavaros, P., & Gorgoulis, V. G. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.02.005 · Cited by 44 · see citing works
Cellular senescence in tissue repair: every cloud has a silver lining
Yun, M. H. (2018) · The International Journal of Developmental Biology · doi:10.1387/ijdb.180081my · Cited by 42 · see citing works
Wang, P., Teng, S., Chengyu, Z., Cui, Z. G., Ma, C., Yu, Y., Lei, Z., Min, M., Zongyi, W., Yang, M., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.05.017 · Cited by 42 · see citing works
Chen, L., Wang, G., Wang, Q., et al. (2019) · PubMed · Cited by 37 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Islam, M. T., Tuday, E., Allen, S., Kim, J., Trott, D. W., Holland, W. L., Donato, A. J., & Lesniewski, L. A. (2023) · Aging Cell · doi:10.1111/acel.13767 · Cited by 313 · see citing works
Algorithmic assessment of cellular senescence in experimental and clinical specimens
Kohli, J., Wang, B., Brandenburg, S. M., Basisty, N., Evangelou, K., Varela-Eirin, M., Campisi, J., Schilling, B., Gorgoulis, V., & Demaria, M. (2021) · Nature Protocols · doi:10.1038/s41596-021-00505-5 · Cited by 196 · see citing works
Self-citationLee, K. S., Lin, S., Copland, D. A., Dick, A. D., & Liu, J. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02088-0 · Cited by 150 · see citing works
Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators
Tao, W., Yu, Z., & Han, J.-D. J. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.009 · Cited by 147 · see citing works
Role of Cellular Senescence in Type II Diabetes
Narasimhan, A., Flores, R. R., Robbins, P. D., & Niedernhofer, L. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab136 · Cited by 133 · see citing works
Recent advances in the discovery of senolytics
Zhang, L., Pitcher, L. E., Prahalad, V., Niedernhofer, L. J., & Robbins, P. D. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111587 · Cited by 115 · see citing works
Age-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice
Liu, J., Zhang, J., Lin, X., Boyce, B. F., Zhang, H., & Xing, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148073 · Cited by 112 · see citing works
GLP1 Receptor Agonists—Effects beyond Obesity and Diabetes
Wilbon, S. S., & Kolonin, M. G. (2023) · Cells · doi:10.3390/cells13010065 · Cited by 101 · see citing works
Novel insights from a multiomics dissection of the Hayflick limit
Chan, M., Yuan, H., Soifer, I., Maile, T. M., Wang, R. Y., Ireland, A., O'Brien, J. J., Goudeau, J., Chan, L. J., Vijay, T., et al. (2022) · eLife · doi:10.7554/elife.70283 · Cited by 99 · see citing works
“Clinical trials for senolytics targeting fibrotic diseases, osteoporosis, frailty, and metabolic syndromes are currently underway ( Borghesan et al., 2020 ).”
Aging conundrum: A perspective for ovarian aging
Wu, J., Liu, Y., Song, Y., Wang, L., Ai, J., & Li, K. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.952471 · Cited by 73 · see citing works
The struggle of a good friend getting old: cellular senescence in viral responses and therapy
Kohli, J., Veenstra, I., & Demaria, M. (2021) · The EMBO Reports · doi:10.15252/embr.202052243 · Cited by 52 · see citing works
Self-citationWang, X., Li, X., Zhou, J., Lei, Z., & Yang, X. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.110890 · Cited by 40 · see citing works
Senopathies-Diseases Associated with Cellular Senescence
Lushchak, O., Schosserer, M., & Grillari, J. (2023) · Biomolecules · doi:10.3390/biom13060966 · Cited by 35 · see citing works
Wang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28 · see citing works
ATP-dependent chromatin remodelers in ageing and age-related disorders
Swer, P. B., & Sharma, R. (2021) · Biogerontology · doi:10.1007/s10522-020-09899-3 · Cited by 25 · see citing works
Research progress on interferon and cellular senescence
Wang, D., Chen, K., Wang, Z., Wu, H., & Li, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202400808rr · Cited by 23 · see citing works
- Authors
- Borghesan, M., Hoogaars, W. M. H., Varela-Eirin, M., Talma, N., & Demaria, M.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Demaria, M.
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 30
- Issue
- 10
- Pages
- 777-791
- ISSN
- 0962-8924 (ISSN-L)
- OpenAlex
- W3048953874
- Cited by
- 267
- References
- 146
- Citations by year
- 2026: 28 · 2025: 67 · 2024: 47 · 2023: 31 · 2022: 46 · 2021: 43 · 2020: 5
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, aging, senescence-associated secretory phenotype, age-related diseases, senotherapeutics, senolytics, therapeutic target, inflammatory cytokines, clinical translation
- MeSH terms
- Animals, Clinical Trials as Topic, Disease, Disease Models, Animal, Humans, Longevity, Models, Biological, Cellular Senescence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
