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Senescence in Health and Disease
Open accessAbstract
Many cellular stresses activate senescence, a persistent hyporeplicative state characterized in part by expression of the p16 INK4a cell-cycle inhibitor. Senescent cell production occurs throughout life and plays beneficial roles in a variety of physiological and pathological processes including embryogenesis, wound healing, host immunity, and tumor suppression. Meanwhile, the steady accumulation of senescent cells with age also has adverse consequences. These non-proliferating cells occupy key cellular niches and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and morbidity. This model suggests that the abundance of senescent cells in vivo predicts "molecular," as opposed to chronologic, age and that senescent cell clearance may mitigate aging-associated pathology.
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“Quiescence is a temporary arrest state with proliferation re-instated by appropriate stimuli; terminal differentiation is the acquisition of specific cellular functions accompanied by a durable cell-cycle arrest mediated by pathways distinct from those of cellular senescence (Figure 2).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The role of senescence in human disease is clear from cellular studies, while in vivo evidence is only now catching up”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Evidence linking senescence to other common age-associated human diseases has recently emerged. These diseases include neurodegenerative disorders, glaucoma, cataract, atherosclerosis and cardiovascular disease, diabetes, osteoarthritis, pulmonary, and renal and liver fibrosis”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In most studies, senescence is assessed in ex vivo cultures or fresh samples by SAb -gal staining or indirect markers in formalin-fixed tissues”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Senescent cells secrete a variety of immunomodulatory and mitogenic cytokines, chemokines, growth, and MMPs [941–943].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [941]
Experimental — accuracy not yet measured
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In the citing paper
“In contrast to the beneficial effects of SASP in the living body, long‐term survival of senescent cells also drives age‐related diseases, such as atherosclerosis, neuropsychiatric disorders, chronic nephritis and cancer.42”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [42]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The drug causes massive apoptosis of senescent cells, which may lead to tissue atrophy [114].”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [114]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This inflammatory signature of potentially senescent-like microglia has been identified in most tissues of all ages in human and mice, but their number increases with age”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as He and Sharpless, 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This initiates and maintains cellular senescence, a key contributor to organismal ageing and multiple age-related diseases6,7.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“In humans, mice and some other species, cellular senescence has been shown to contribute to various physiological and pathological processes1.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“This cell-cycle withdrawal differs from quiescence and terminal differentiation (He and Sharpless, 2017).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
The cited source says what the claim attributes to it.
In the citing paper
“Quiescence is a temporary arrest state with proliferation re-instated by appropriate stimuli; terminal differentiation is the acquisition of specific cellular functions accompanied by a durable cell-cycle arrest mediated by pathways distinct from those of cellular senescence (Figure 2).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as He and Sharpless, 2017
The cited source says what the claim attributes to it.
In the citing paper
“Although such a senescence-associated secretory phenotype (SASP) appears to be involved in the immunological clearance of senescent cells, it also affects the biology of neighboring cells with an intact proliferative potential (and this has major implications for senescence-inducing anticancer agents) [941–945].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [941]
The cited source says what the claim attributes to it.
In the citing paper
“Accumulation of senescent cells is causally linked to functional decline in aging tissues.”
From Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging (2024) · cites this paper as [25]
The cited source says what the claim attributes to it.
In the citing paper
“Senescent cells accumulate inside the body during aging4,8”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [8]
In the citing paper
“However, expression of p21WAF1/CIP1 does not persist in senescent cells as it is mainly required for induction of senescence (Stein et al., 1999; Sharpless and Sherr, 2015; He and Sharpless, 2017; Song et al., 2020).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as He and Sharpless, 2017
In the citing paper
“At the biochemical level, cellular senescence is often characterized by: (1) increased lysosomal galactosidase beta 1 (GLB1) activity; (2) inhibition of multiple cyclin-dependent kinases (CDKs) and consequent dephosphorylation of various members of the retinoblastoma (RB) protein family—including RB transcriptional corepressor 1 (RB1), RB transcriptional corepressor like 1 (RB1L; best known as p”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [941]
In the citing paper
“Mounting evidence, however, indicates that senescent cells accumulate during organismal aging due to their increased generation coupled to inefficient clearance [935, 941, 960, 961].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [941]
In the citing paper
“Senescent cells exhibit a senescence-associated secretory phenotype (SASP) characterized by an overproduction of proinflammatory molecules such as IL6, TGFβ, IL8, MCP-1, extracellular matrix remodeling enzymes (MMPs), serine/cysteine proteinase inhibitors (serpins), and tissue inhibitors of metalloproteinases (61).”
From Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 (2021) · cites this paper as [61]
In the citing paper
“Ageing is arguably primarily characterised by the accumulation of cells which have undergone the process of permanent cell cycle arrest, termed senescence (9).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [9]
In the citing paper
“Cellular senescence, which was initially described by Leonard Hayflick and colleagues in 1961,1 plays crucial roles in a variety of physiological and pathological processes, including embryonic development, cancer, aging, and multiple other diseases.2,3,4,5,6,7”
From Identifying specific functional roles for senescence across cell types (2024) · cites this paper as [3]
In the citing paper
“Not only is this condition in common for regenerating tissues in the early phase, but it also somehow mimics the senescence-associated secretory phenotype (SASP) of presenescent and senescent cells. It appears to be beneficial if intermittent, but it causes pathology if chronically active.”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [126]
In the citing paper
“These studies demonstrated that senescence is one of the major drivers of aging and that clearing senescent cells is a promising approach to treat age-related diseases and improve physical function.6,10”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [10]
In the citing paper
“Senescence was traditionally considered an innate anti-cancer mechanism as it can serve to eliminate damaged cells,3,5 whereby activation of the senescence programme in cells harbouring oncogenic mutations serves as a tumour suppressor mechanism, preventing the expansion of these mutated cells and progression into malignancies.3,5”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [3]
In the citing paper
“Cells undergoing damage-induced senescence are often cleared by the immune system, as several SASP factors are cytokines and chemokines that can modulate the local immune environment.2,3,5,70,71”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [3]
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Citations
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
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Mutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419
Genome-wide methylation profiles reveal quantitative views of human aging rates
Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., Gao, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.016 · Cited by 4,270
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
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
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954
Naturally 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 2,876
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Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
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
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Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
Cellular 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
Senolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098
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Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
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Fane, M., & Weeraratna, A. T. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0222-9 · Cited by 849
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Coryell, P. R., Diekman, B. O., & Loeser, R. F. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-00533-7 · Cited by 761
Telomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754
mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review
Weichhart, T. (2018) · Gerontology · doi:10.1159/000484629 · Cited by 596
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631
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
Banales, J. M., Huebert, R. C., Karlsen, T., Strazzabosco, M., LaRusso, N. F., & Gores, G. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0125-y · Cited by 517
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499
Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk
Chia, C. W., Egan, J. M., & Ferrucci, L. (2018) · Circulation Research · doi:10.1161/circresaha.118.312806 · Cited by 454
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Geirsdottir, L., David, E., Keren-Shaul, H., Weiner, A., Bohlen, S. C., Neuber, J., Balic, A., Giladi, A., Sheban, F., Dutertre, C.-A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.010 · Cited by 461
Endothelial cell senescence in aging-related vascular dysfunction
Jia, G., Aroor, A. R., Jia, C., & Sowers, J. R. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.008 · Cited by 454
Novais, E. J., Tran, V. A., Johnston, S. N., Darris, K. R., Roupas, A. J., Sessions, G. A., Shapiro, I. M., Diekman, B. O., & Risbud, M. V. (2021) · Nature Communications · doi:10.1038/s41467-021-25453-2 · Cited by 440
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
Johmura, Y., Yamanaka, T., Omori, S., Wang, T.-W., Sugiura, Y., Matsumoto, M., Suzuki, N., Kumamoto, S., Yamaguchi, K., Hatakeyama, S., et al. (2021) · Science · doi:10.1126/science.abb5916 · Cited by 440
Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442
Source of chronic inflammation in aging
Sanada, F., Taniyama, Y., Muratsu, J., Otsu, R., Shimizu, H., Rakugi, H., & Morishita, R. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00012 · Cited by 413
Biomarkers of cellular senescence and skin aging
Wang, A. S., & Dreesen, O. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00247 · Cited by 404
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408
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
TGF-β Signaling in Cellular Senescence and Aging-Related Pathology
Tominaga, K., & Suzuki, H. I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205002 · Cited by 393
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03555-8 · Cited by 350
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
Elyahu, Y., Hekselman, I., Eizenberg-Magar, I., Berner, O., Strominger, I., Schiller, M., Mittal, K., Nemirovsky, A., Eremenko, E., Vital, A., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw8330 · Cited by 324
The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice
Xu, Q., Fu, Q., Li, Z., Liu, H., Wang, Y., Lin, X., He, R., Zhang, X., Ju, Z., Campisi, J., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00491-8 · Cited by 341
Borghesan, M., Fafián-Labora, J., Eleftheriadou, O., Carpintero-Fernández, P., Paez-Ribes, M., Vizcay-Barrena, G., Swisa, A., Kolodkin-Gal, D., Ximénez-Embún, P., Lowe, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.095 · Cited by 315
“In fact, an enrichment in the number of senescent cells has been observed in vivo during both biological and pathological processes such as development, cancer, fibrosis, and wound healing (He and Sharpless, 2017; Muñoz-Espı́n and Serrano, 2014).”
BackgroundFerrucci, L., Levine, M. E., Kuo, P.-L., & Simonsick, E. M. (2018) · Circulation Research · doi:10.1161/circresaha.118.312816 · Cited by 303
Cells exhibiting strong p16 INK4a promoter activation in vivo display features of senescence
Liu, J.-Y., Souroullas, G. P., Diekman, B. O., Krishnamurthy, J., Hall, B. M., Sorrentino, J. A., Parker, J. S., Sessions, G. A., Gudkov, A. V., & Sharpless, N. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818313116 · Cited by 306
Self-citationThe influence of evolutionary history on human health and disease
Benton, M. L., Abraham, A., LaBella, A. L., Abbot, P., Rokas, A., & Capra, J. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00305-9 · Cited by 291
Aging of the cells: Insight into cellular senescence and detection Methods.
Mohamad Kamal, N. S., Safuan, S., Shamsuddin, S., & Foroozandeh, P. (2020) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2020.151108 · Cited by 287
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275
Ito, T., Teo, Y. V., Evans, S. A., Neretti, N., & Sedivy, J. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.002 · Cited by 265
Cellular senescence and Alzheimer disease: the egg and the chicken scenario
Saez-Atienzar, S., & Masliah, E. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0325-z · Cited by 257
Zhu, Y., Liu, X., Ding, X., Wang, F., & Geng, X. (2019) · Biogerontology · doi:10.1007/s10522-018-9769-1 · Cited by 255
Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer
Haston, S., Gonzalez-Gualda, E., Morsli, S., Ge, J., Reen, V., Calderwood, A., Moutsopoulos, I., Panousopoulos, L., Deletic, P., Carreno, G., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.004 · Cited by 251
D’Agnillo, F., Walters, K.-A., Xiao, Y., Sheng, Z.-M., Scherler, K., Park, J., Gygli, S., Rosas, L. A., Sadtler, K., Kalish, H., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abj7790 · Cited by 237
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232
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Senescent cell turnover slows with age providing an explanation for the Gompertz law
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Diekman, B. O., Sessions, G. A., Collins, J. A., Knecht, A. K., Strum, S. L., Mitin, N. K., Carlson, C. S., Loeser, R. F., & Sharpless, N. E. (2018) · Aging Cell · doi:10.1111/acel.12771 · Cited by 158
Self-citationHistone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence
Sen, P., Lan, Y., Li, C. Y., Sidoli, S., Donahue, G., Dou, Z., Frederick, B., Chen, Q., Luense, L. J., Garcia, B. A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.021 · Cited by 164
Ritzel, R. M., Doran, S. J., Glaser, E. P., Meadows, V. E., Faden, A. I., Stoica, B. A., & Loane, D. J. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.02.010 · Cited by 156
Muñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124716 · Cited by 162
Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160
Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
Ma, S., Ji, Z., Zhang, B., Geng, L., Cai, Y., Nie, C., Li, J., Zuo, Y., Sun, Y., Xu, G., et al. (2024) · Cell · doi:10.1016/j.cell.2024.10.019 · Cited by 162
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153
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
Poblocka, M., Bassey, A. L., Smith, V. M., Falcicchio, M., Manso, A. S., Althubiti, M., Sheng, X., Kyle, A., Barber, R., Frigerio, M., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99852-2 · Cited by 137
Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019) · Nature Reviews Chemistry · doi:10.1038/s41570-019-0108-0 · Cited by 140
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
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
Cell senescence contributes to tissue regeneration in zebrafish
Da Silva‐Álvarez, S., Guerra‐Varela, J., Sobrido‐Cameán, D., Quelle, A., Barreiro‐Iglesias, A., Sánchez, L., & Collado, M. (2020) · Aging Cell · doi:10.1111/acel.13052 · Cited by 126
Mouse Models to Disentangle the Hallmarks of Human Aging
Folgueras, A. R., Freitas-Rodríguez, S., Velasco, G., & López-Otín, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312204 · Cited by 113
Ryu, Y. S., Kang, K. A., Piao, M. J., Ahn, M. J., Yi, J. M., Bossis, G., Hyun, Y.-M., Park, C. O., & Hyun, J. W. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0305-4 · Cited by 119
Ye, G., Xie, Z., Zeng, H., Wang, P., Li, J., Zheng, G., Wang, S., Cao, Q., Li, M., Liu, W., et al. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-02993-x · Cited by 115
Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models
Dai, H., Zhu, C., Huai, Q., Xu, W., Zhu, J., Zhang, X., Zhang, X., Sun, B., Xu, H., Zheng, M., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.034 · Cited by 114
Xu, P., Wang, M., Song, W.-M., Wang, Q., Yuan, G.-C., Sudmant, P. H., Zare, H., Tu, Z., Orr, M. E., & Zhang, B. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00507-7 · Cited by 114
Cell senescence in liver diseases: pathological mechanism and theranostic opportunity
Sanfeliu-Redondo, D., Gibert-Ramos, A., & Gracia-Sancho, J. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00913-4 · Cited by 117
Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis
Liu, X., Chai, Y., Liu, G., Su, W., Guo, Q., Lv, X., Gao, P., Yu, B., Ferbeyre, G., Cao, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22131-1 · Cited by 116
Targeting 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
Abdul-Aziz, A. M., Sun, Y., Hellmich, C., Marlein, C. R., Mistry, J., Forde, E., Piddock, R. E., Shafat, M. S., Morfakis, A., Mehta, T., et al. (2019) · Blood · doi:10.1182/blood-2018-04-845420 · Cited by 105
Hepatic senescence, the good and the bad
Huda, N., Liu, G., Hong, H., Yan, S., Khambu, B., & Yin, X.-M. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i34.5069 · Cited by 100
Tsuji, S., Minami, S., Hashimoto, R., Konishi, Y., Suzuki, T., Kondo, T., Sasai, M., Torii, S., Ono, C., Shichinohe, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00170-7 · Cited by 84
Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2
Cheng, N., Kim, K.-H., & Lau, L. F. (2022) · JCI Insight · doi:10.1172/jci.insight.158207 · Cited by 87
Bacterial induction of B cell senescence promotes age-related changes in the gut microbiota
Kawamoto, S., Uemura, K., Hori, N., Takayasu, L., Konishi, Y., Katoh, K., Matsumoto, T., Suzuki, M., Sakai, Y., Matsudaira, T., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01145-5 · Cited by 91
Short-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80
Is exercise a senolytic medicine? A systematic review
Chen, X., Yi, Z., Wong, G. T., Hasan, K. M. M., Kwan, J. S., Ma, A. C., & Chang, R. C. (2021) · Aging Cell · doi:10.1111/acel.13294 · Cited by 88
Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2018) · Biogerontology · doi:10.1007/s10522-018-9762-8 · Cited by 84
ATF3 drives senescence by reconstructing accessible chromatin profiles
Zhang, C., Zhang, X., Huang, L., Guan, Y., Huang, X., Tian, X., Zhang, L., & Tao, W. (2021) · Aging Cell · doi:10.1111/acel.13315 · Cited by 84
“Senescent cells play intricate roles in many biological processes including tumor suppression, embryogenesis, tissue repair, host immunity, aging and age-related disorders(Chou & Effros, 2013; He & Sharpless, 2017; Jun & Lau, 2010; Munoz-Espin et al., 2013; Reddel, 2009; Storer et al., 2013).”
BackgroundCellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review
Amaya-Montoya, M., Pérez-Londoño, A., Guatibonza-García, V., Vargas-Villanueva, A., & Mendivil, C. O. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01287-0 · Cited by 82
A Blueprint for Characterizing Senescence
Roy, A. L., Sierra, F., Howcroft, K., Singer, D. S., Sharpless, N., Hodes, R. J., Wilder, E. L., & Anderson, J. M. (2020) · Cell · doi:10.1016/j.cell.2020.10.032 · Cited by 81
Self-citationInvariant natural killer T cells coordinate removal of senescent cells
Arora, S., Thompson, P. J., Wang, Y., Bhattacharyya, A., Apostolopoulou, H., Hatano, R., Naikawadi, R. P., Shah, A., Wolters, P. J., Koliwad, S., et al. (2021) · Med · doi:10.1016/j.medj.2021.04.014 · Cited by 77
Wlaschek, M., Singh, K., Sindrilaru, A., Crisan, D., & Scharffetter-Kochanek, K. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.036 · Cited by 76
“portant molecular mechanism in physiological wound healing and development [111,112].”
BackgroundEmbryonic senescent cells re-enter cell cycle and contribute to tissues after birth
Li, Y., Zhao, H., Huang, X., Tang, J., Zhang, S., Li, Y., Liu, X., He, L., Ju, Z., Lui, K. O., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0050-6 · Cited by 71
Characterization of cellular senescence in doxorubicin-induced aging mice
Sun, T., Zhang, L., Feng, J., Bao, L., Wang, J., Song, Z., Mao, Z., Li, J., & Hu, Z. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111800 · Cited by 73
Miyata, K., Imai, Y., Hori, S., Nishio, M., Loo, T. M., Okada, R., Yang, L., Nakadai, T., Maruyama, R., Fujii, R., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025647118 · Cited by 74
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
Cellular Senescence in Idiopathic Pulmonary Fibrosis
Kellogg, D. L., Kellogg, D. L., Musi, N., & Nambiar, A. M. (2021) · Current Molecular Biology Reports · doi:10.1007/s40610-021-00145-4 · Cited by 67
Fatt, M. P., Tran, L. M., Vetere, G., Storer, M. A., Simonetta, J. V., Miller, F. D., Frankland, P. W., & Kaplan, D. R. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.12.010 · Cited by 58
“First, western blot analysis of similar cultures showed that P16INK4A levels were increased 4.1 ± 0.4-fold with camptothecin (Figures 3C and 3D).”
BackgroundInfluentialBientinesi, E., Lulli, M., Becatti, M., Ristori, S., Margheri, F., & Monti, D. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111689 · Cited by 61
Cytoplasmic chromatin fragments-from mechanisms to therapeutic potential.
Miller, K. N., Dasgupta, N., Liu, T., Adams, P. D., & Vizioli, M. G. (2021) · eLife · doi:10.7554/elife.63728 · Cited by 55
Azazmeh, N., Assouline, B., Winter, E., Ruppo, S., Nevo, Y., Maly, A., Meir, K., Witkiewicz, A. K., Cohen, J., Rizou, S. V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16475-3 · Cited by 57
Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
Alessio, N., Squillaro, T., Di Bernardo, G., Galano, G., De Rosa, R., Melone, M. A., Peluso, G., & Galderisi, U. (2020) · eLife · doi:10.7554/elife.54523 · Cited by 51
Kaur, G., Muthumalage, T., & Rahman, I. (2023) · Aging Cell · doi:10.1111/acel.13850 · Cited by 53
Martini, H., Iacovoni, J. S., Maggiorani, D., Dutaur, M., Marsal, D. J., Roncalli, J., Itier, R., Dambrin, C., Pizzinat, N., Mialet‐Perez, J., et al. (2019) · Aging Cell · doi:10.1111/acel.13015 · Cited by 51
Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain
Santoro, A., Spinelli, C. C., Martucciello, S., Nori, S. L., Capunzo, M., Puca, A. A., & Ciaglia, E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0118-003r · Cited by 50
Metadata
- Authors
- He, S., & Sharpless, N. E.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Sharpless, Norman E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 169
- Issue
- 6
- Pages
- 1000-1011
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5643029
- OpenAlex
- W2620914886
- Cited by
- 1,766
- References
- 107
- Citations by year
- 2026: 173 · 2025: 232 · 2024: 240 · 2023: 266 · 2022: 228 · 2021: 225 · 2020: 157 · 2019: 128 · 2018: 102 · 2017: 14
- FWCI
- 13.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Glenn Foundation
- Breast Cancer Research Foundation
- Burroughs Wellcome Foundation
- NIH (CA203023, AG024379)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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, senolytics, senescent cell clearance, aging, age-related diseases, inflammatory cytokines, tumor suppression, wound healing, embryonic development, host immunity, cell cycle inhibitors
- MeSH terms
- Aging, Animals, Cell Cycle, Humans, Neoplasms, Wound Healing, Cellular Senescence
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