Impact of Senescent Cell Subtypes on Tissue Dysfunction and Repair: Importance and Research Questions
Open accessAbstract
Cellular senescence, first observed and defined through cell culture studies, is a cell fate associated with essentially permanent cell cycle arrest and that can be triggered by a variety of inducers. Emerging evidence suggests senescence is a dynamic process with diverse functional characteristics. Depending on the tissue, type of inducer, and time since induction, senescent cells can promote tissue repair and re-modeling, prevent tumor development, or contribute to age-related disorders and chronic diseases, including cancers. Senescent cell characteristics appear to depend on multiple factors and be influenced by the milieu and other senescent cells locally and at a distance. We review diverse phenotypes of senescent cells originating from different cell types, senescence inducers over time since induction of senescence, and across conditions and diseases. This background is essential to inform further understanding about senescent cell subtypes and will point towards rational senescence-modulating strategies for achieving therapeutic benefit.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Transient senescent cells can have beneficial functions: their SASPs can orchestrate tissue remodeling, induce immune responses during infection or injury, promote parturition via placental senescent cells, and attract immune cells to clear pro-inflammatory senescent cells.
“If senescent cells are present transiently, beneficial functions of both the proapoptotic and pro-growth types of SASP can orchestrate tissue remodeling”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [61]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn the other 30-70% of senescent cells, the SASP appears to contain growth and regenerative factors, may cause less apoptosis, tissue destruction, and fibrosis, and can contribute to tissue repair via factors such as VEGF-A and PDGF-AA.
“In the other 30–70% of senescent cells, the SASP appears to comprise growth and other regenerative factors, potentially causing less apoptosis, tissue destruction and fibrosis than proapoptotic, pro-inflammatory senescent cells and can even contribute to tissue repair (for example, through the growth factors VEGF-A and PDGF-AA)61,65.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [61]
In “Anti-apoptotic defenses vary among senescent cells” (page unavailable), the paper estimates that deleterious cells may comprise 30–70% of senescent cells and says the remaining helper cells release fewer pro-apoptotic factors and might aid wound healing through PDGF-AA. “Type of inducers” (page unavailable) also describes VEGF secretion by senescent fibroblasts, but does not identify those fibroblasts as helper cells. The paper does not specifically say that helper cells cause less fibrosis than deleterious cells. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn 30-70% of senescent cells, the SASP contains pro-inflammatory, proapoptotic, and pro-fibrotic factors, some of which can make previously non-senescent cells senescent locally and at a distance through endocrine action.
“In 30–70% of senescent cells, this SASP entails pro-inflammatory, proapoptotic and pro-fibrotic factors7,31,40,59–64, some of which can cause previously non-senescent cells to become senescent both locally and at a distance in an endocrine manner24,39,47.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [61]
The “Anti-apoptotic defenses vary among senescent cells” section says pro-inflammatory and pro-apoptotic D-senescent cells may comprise about 30–70% of senescent cells, based on unpublished observations; it does not include pro-fibrotic factors in that description. The “Endocrine and paracrine impact of the SASP” section says SASP factors can spread senescence to previously normal cells locally and in distant organs. The claim is therefore supported in part, but states the tentative percentage more firmly and adds an unsupported pro-fibrotic component. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSASP factors, senescence markers, and markers of other aging processes such as α-Klotho can be assayed in body fluids including urine, saliva, blood, and cerebrospinal fluid.
“SASP factors, senescence markers and markers of other fundamental aging processes (for example, α-Klotho) can be assayed in body fluids such as urine, saliva, blood or cerebrospinal fluid7,19,48,59,61,64,132,133.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [61]
The sections on SASP differences and endocrine effects (page unavailable) discuss SASP factors and senescence markers, but do not say they can be assayed in body fluids. Searches for urine, saliva, blood, cerebrospinal fluid, α-Klotho, and circulating biomarkers found no passage addressing the claimed assays. (LLM, conf=0.73)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · see citing works
The 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 7× · see citing works
“Dasatinib targets, among others, dependence receptor/Src kinase SCAPs, while quercetin targets the BCL-2/BCL-xL, PI3K/ AKT, and p53/p21 CIP1 /serpine SCAPs [5].”
InfluentialSelf-citationSenolytics 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
Self-citationAn 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
Clearance 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
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 1× · see citing works
“Similarly, the chemokine receptor CXCR2 and its ligand, GRO-α , can be upregulated in senescent cells, contributing to the formation of a network that reinforces growth arrest in a p53-dependent manner [55].”
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
Self-citationMechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · 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
“…6) improved pulmonary function and reduced pulmonary fibrosis in mice with bleomycin-induced lung damage, a model of idiopathic pulmonary fibrosis [71]; 7) improved physical function and increased median lifespan in old mice [53, 73]; 8) improved cardiac ejection fraction and fractional…”
Self-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
Programmed cell senescence during mammalian embryonic development
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.019 · Cited by 1,428 · see citing works
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255 · see citing works
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Senolytic drugs: from discovery to translation
Kirkland, J. L., & Tchkonia, T. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13141 · Cited by 1,227 · see citing works
Self-citationRapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity
Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199 · see citing works
Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
Glück, S., Guey, B., Gulen, M. F., Wolter, K., Kang, T.-W., Schmacke, N. A., Bridgeman, A., Rehwinkel, J., Zender, L., & Ablasser, A. (2017) · Nature Cell Biology · doi:10.1038/ncb3586 · Cited by 1,196 · cited 1× · see citing works
“An intracellular IL-1 α / miR-146a/b/ IL-6/ C/EBP-β loop [41] and related p38/NF-κ B [42], cGAS/STING [43], and mTOR-mediated pathways [44] appear to contribute to the changes in gene expression that result in the SASP [2].”
Senescent 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
Laberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., Pirtskhalava, T., Giorgadze, N., Johnson, K. O., Giles, C. B., et al. (2016) · Aging Cell · doi:10.1111/acel.12445 · Cited by 1,148 · see citing works
Self-citationCellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044 · see citing works
Self-citationFreund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · cited 1× · see citing works
“An intracellular IL-1 α / miR-146a/b/ IL-6/ C/EBP-β loop [41] and related p38/NF-κ B [42], cGAS/STING [43], and mTOR-mediated pathways [44] appear to contribute to the changes in gene expression that result in the SASP [2].”
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
Self-citationFeedback 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 1× · see citing works
“The growth arrest of senescent cells is related to increased p16 INK4A or p21 CIP1 , which are inhibitors of the cyclin/cyclin-dependent kinase (CDK) complexes that mediate cell cycle progression, and this may or may not involve activation of p53 [39].”
Alcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13742 · Cited by 1,008 · see citing works
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · 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
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 1× · see citing works
“JAK-STAT3 inhibition leads to reprogramming of the SASP, which decreases frailty and bone loss in old animals [50].”
Self-citationA crucial role for adipose tissue p53 in the regulation of insulin resistance
Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., et al. (2009) · Nature Medicine · doi:10.1038/nm.2014 · Cited by 891 · 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
Self-citationRoos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., Hagler, M., Jurk, D., Smith, L. A., Casaclang‐Verzosa, G., et al. (2016) · Aging Cell · doi:10.1111/acel.12458 · Cited by 738 · see citing works
Self-citationIdentification 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
Self-citationLucas, C. L., Kuehn, H. S., Zhao, F. R., Niemela, J. E., Deenick, E. K., Palendira, U., Avery, D. T., Moens, L., Cannons, J. L., Biancalana, M., et al. (2013) · Nature Immunology · doi:10.1038/ni.2771 · Cited by 677 · 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-citationOrjalo, A. V., Bhaumik, D., Gengler, B. K., Scott, G. K., & Campisi, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905299106 · Cited by 654 · see citing works
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654 · see citing works
The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.
Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., Sansom, O. J., Zender, L., & Keyes, W. M. (2017) · Genes & Development · doi:10.1101/gad.290635.116 · Cited by 650 · see citing works
Senescent cells as a source of inflammatory factors for tumor progression
Davalos, A. R., Coppe, J.-P., Campisi, J., & Desprez, P.-Y. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9220-9 · Cited by 636 · see citing works
Secretion 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
Targeting senescent cells enhances adipogenesis and metabolic function in old age
Xu, M., Palmer, A. K., Ding, H., Weivoda, M. M., Pirtskhalava, T., White, T. A., Sepe, A., Johnson, K. O., Stout, M. B., Giorgadze, N., et al. (2015) · eLife · doi:10.7554/elife.12997 · Cited by 604 · see citing works
Self-citationJurk, D., Wang, C., Miwa, S., Maddick, M., Korolchuk, V., Tsolou, A., Gonos, E. S., Thrasivoulou, C., Jill Saffrey, M., Cameron, K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00870.x · Cited by 598 · 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
Self-citationLength-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 2× · see citing works
“…fate that entails an essentially permanent cell cycle arrest in response to multiple factors, including repeated replication, potentially oncogenic mutations and activated oncogenes, DNA damage, metabolic insults, damage/danger signals, neutrophils, radiation, and cytotoxic and other drugs [1–4].”
Self-citationThe role of cellular senescence in ageing and endocrine disease
Khosla, S., Farr, J. N., Tchkonia, T., & Kirkland, J. L. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0335-y · Cited by 523 · see citing works
Self-citationBhaumik, D., Scott, G. K., Schokrpur, S., Patil, C. K., Orjalo, A. V., Rodier, F., Lithgow, G. J., & Campisi, J. (2009) · Aging · doi:10.18632/aging.100042 · Cited by 500 · see citing works
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · see citing works
Self-citation(1995) · PubMed · Cited by 496 · see citing works
Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
Bitto, A., Ito, T. K., Pineda, V. V., LeTexier, N. J., Huang, H. Z., Sutlief, E., Tung, H., Vizzini, N., Chen, B., Smith, K., et al. (2016) · eLife · doi:10.7554/elife.16351 · Cited by 474 · see citing works
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415 · see citing works
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I. I., et al. (2017) · Aging · doi:10.18632/aging.101268 · Cited by 407 · see citing works
Ogrodnik, M., Evans, S. A., Fielder, E., Victorelli, S., Kruger, P., Salmonowicz, H., Weigand, B. M., Patel, A. D., Pirtskhalava, T., Inman, C. L., et al. (2021) · Aging Cell · doi:10.1111/acel.13296 · Cited by 405 · see citing works
Self-citationThe senescence-associated secretome as an indicator of age and medical risk
Schafer, M. J., Zhang, X., Kumar, A., Atkinson, E. J., Zhu, Y., Jachim, S., Mazula, D. L., Brown, A. K., Berning, M., Aversa, Z., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.133668 · Cited by 401 · see citing works
Cai, 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
Dimri, G. P., Itahana, K., Acosta, M., & Campisi, J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.273-285.2000 · Cited by 393 · 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
Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism
Wang, R., Yu, Z., Sunchu, B., Shoaf, J., Dang, I., Zhao, S., Caples, K., Bradley, L., Beaver, L. M., Ho, E., et al. (2017) · Aging Cell · doi:10.1111/acel.12587 · Cited by 360 · 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 · cited 1× · see citing works
“In drug screens using models of oncogene-induced senescence in normal cells vs. therapy-induced senescent cells, cardiac glycosides (CGs) were identified as a class of senolytics [67, 68].”
Senolytics reduce coronavirus-related mortality in old mice
Camell, C. D., Yousefzadeh, M. J., Zhu, Y., Prata, L. G. P. L., Huggins, M. A., Pierson, M., Zhang, L., O’Kelly, R. D., Pirtskhalava, T., Xun, P., et al. (2021) · Science · doi:10.1126/science.abe4832 · Cited by 320 · see citing works
Self-citationKim, K.-H., Chen, C.-C., Monzon, R. I., & Lau, L. F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00049-13 · Cited by 261 · see citing works
Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction
Victorelli, S., Lagnado, A., Halim, J., Moore, W., Talbot, D., Barrett, K., Chapman, J., Birch, J., Ogrodnik, M., Meves, A., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2019101982 · Cited by 258 · see citing works
Glucocorticoids suppress selected components of the senescence‐associated secretory phenotype
Laberge, R., Zhou, L., Sarantos, M. R., Rodier, F., Freund, A., de Keizer, P. L. J., Liu, S., Demaria, M., Cong, Y., Kapahi, P., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00818.x · Cited by 229 · see citing works
Biology of premature ageing in survivors of cancer
Cupit-Link, M. C., Kirkland, J. L., Ness, K. K., Armstrong, G. T., Tchkonia, T., LeBrasseur, N. K., Armenian, S. H., Ruddy, K. J., & Hashmi, S. K. (2017) · ESMO Open · doi:10.1136/esmoopen-2017-000250 · Cited by 214 · see citing works
Self-citationIske, J., Seyda, M., Heinbokel, T., Maenosono, R., Minami, K., Nian, Y., Quante, M., Falk, C. S., Azuma, H., Martin, F., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18039-x · Cited by 211 · see citing works
Self-citationNeutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
Lagnado, A., Leslie, J., Ruchaud‐Sparagano, M., Victorelli, S., Hirsova, P., Ogrodnik, M., Collins, A. L., Vizioli, M. G., Habiballa, L., Saretzki, G., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106048 · Cited by 211 · see citing works
Self-citationSenolytics and senostatics as adjuvant tumour therapy
Short, S. C., Fielder, E., Miwa, S., & von Zglinicki, T. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.056 · Cited by 201 · 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
The Signaling of Cellular Senescence in Diabetic Nephropathy
Xiong, Y., & Zhou, L. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/7495629 · Cited by 185 · see citing works
Senescence in Post-Mitotic Cells: A Driver of Aging?
von Zglinicki, T., Wan, T., & Miwa, S. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8048 · Cited by 170 · see citing works
Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions
Pezze, P. D., Nelson, G., Otten, E. G., Korolchuk, V. I., Kirkwood, T. B. L., von Zglinicki, T., & Shanley, D. P. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003728 · Cited by 162 · see citing works
Senescent cell turnover slows with age providing an explanation for the Gompertz law
Karin, O., Agrawal, A., Porat, Z., Krizhanovsky, V., & Alon, U. (2019) · Nature Communications · doi:10.1038/s41467-019-13192-4 · Cited by 151 · see citing works
Ness, K. K., Kirkland, J. L., Gramatges, M. M., Wang, Z., Kundu, M., McCastlain, K., Li-Harms, X., Zhang, J., Tchkonia, T., Pluijm, S. M. F., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.7467 · Cited by 140 · see citing works
Self-citationAlibhai, F. J., Lim, F., Yeganeh, A., DiStefano, P. V., Marvasti, T. B., Belfiore, A., Wlodarek, L., Gustafson, D., Millar, S., Li, S., et al. (2020) · Aging Cell · doi:10.1111/acel.13103 · Cited by 139 · see citing works
Badi, I., Burba, I., Ruggeri, C., Zeni, F., Bertolotti, M., Scopece, A., Pompilio, G., & Raucci, A. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu180 · Cited by 134 · see citing works
Sharma, A. K., Roberts, R. L., Benson, R. D., Pierce, J. L., Yu, K., Hamrick, M. W., & McGee-Lawrence, M. E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00354 · Cited by 131 · cited 1× · see citing works
“Indeed, drugs with single or limited targets, such as navitoclax, have off-target apoptotic effects on multiple nonsenescent cell types, limiting clinical translation or requiring local application rather than systemic delivery, such as oral administration [77].”
Deterioration of nuclear morphology and architecture: A hallmark of senescence and aging
Pathak, R. U., Soujanya, M., & Mishra, R. K. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101264 · Cited by 119 · see citing works
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence
Parry, A. J., Hoare, M., Bihary, D., Hänsel-Hertsch, R., Smith, S., Tomimatsu, K., Mannion, E., Smith, A., D’Santos, P., Russell, I. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04283-9 · Cited by 102 · see citing works
The role of senescent T cells in immunopathology
Covre, L. P., De Maeyer, R. P. H., Gomes, D. C. O., & Akbar, A. N. (2020) · Aging Cell · doi:10.1111/acel.13272 · Cited by 93 · see citing works
Regulation and Consequences of cGAS Activation by Self-DNA
Zierhut, C., & Funabiki, H. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.05.006 · Cited by 89 · see citing works
MicroRNA‐570 is a novel regulator of cellular senescence and inflammaging
Baker, J. R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P. S., Donnelly, L., Ito, K., & Barnes, P. J. (2018) · The FASEB Journal · doi:10.1096/fj.201800965r · Cited by 88 · see citing works
Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells
Beyne‐Rauzy, O., Récher, C., Dastugue, N., Demur, C., Pottier, G., Laurent, G., Sabatier, L., & Mas, V. M. (2004) · Oncogene · doi:10.1038/sj.onc.1208024 · Cited by 74 · see citing works
Induction and Validation of Cellular Senescence in Primary Human Cells
Hernandez‐Segura, A., Brandenburg, S. M., & Demaria, M. (2018) · Journal of Visualized Experiments · doi:10.3791/57782 · Cited by 58 · see citing works
Čubro, H., Nath, K. A., Suvakov, S. R., Valencia, O. A. G., Parashuram, S., White, W., Weissgerber, T. L., Nath, M. C., Milic, N. M., Sontag, F., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.09.034 · Cited by 23 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Cellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,105 · see citing works
Self-citationTargeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity
Wang, L., Wang, B., Gasek, N. S., Zhou, Y., Cohn, R. L., Martin, D. E., Zuo, W., Flynn, W. F., Guo, C., Jellison, E. R., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.11.002 · Cited by 163 · see citing works
Self-citationTargeting senescent cells for a healthier longevity: the roadmap for an era of global aging
Sun, Y., Li, Q., & Kirkland, J. L. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac030 · Cited by 105 · see citing works
Self-citationRole of senescence in the chronic health consequences of COVID-19
Wissler Gerdes, E. O., Vanichkachorn, G., Verdoorn, B. P., Hanson, G. J., Joshi, A. Y., Murad, M. H., Rizza, S. A., Hurt, R. T., Tchkonia, T., & Kirkland, J. L. (2022) · Translational Research · doi:10.1016/j.trsl.2021.10.003 · Cited by 38 · see citing works
Self-citation
- Authors
- Tripathi, U., Misra, A., Tchkonia, T., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Kirkland, James L.
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 198
- Pages
- 111548
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC8373827
- OpenAlex
- W3193165141
- Cited by
- 104
- References
- 82
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 17 · 2023: 21 · 2022: 10 · 2021: 6
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mechanisms of Ageing and Development (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01 AG62413, R01 AG072301, R01 AG61414, R33 AG61456, R37 AG13925, UH3 AG56933)
- Noaber Foundation
- 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, tissue repair, tissue remodeling, tumor suppression, age-related diseases, chronic disease, paracrine senescence
- MeSH terms
- Senescence-Associated Secretory Phenotype, Aging, Cell Cycle, Cells, Chronic Disease, Humans, Regeneration, 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
