The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
The role of senescent cells in ageing
Open accessAbstract
Cellular senescence has historically been viewed as an irreversible cell-cycle arrest mechanism that acts to protect against cancer, but recent discoveries have extended its known role to complex biological processes such as development, tissue repair, ageing and age-related disorders. New insights indicate that, unlike a static endpoint, senescence represents a series of progressive and phenotypically diverse cellular states acquired after the initial growth arrest. A deeper understanding of the molecular mechanisms underlying the multi-step progression of senescence and the development and function of acute versus chronic senescent cells may lead to new therapeutic strategies for age-related pathologies and extend healthy lifespan.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Cellular senescence is an evolutionarily conserved state of stable replicative arrest induced by pro-ageing stressors also implicated in IPF pathogenesis, including telomere attrition, oxidative stress, DNA damage and proteome instability.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [8]
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
“Through secretion of the senescence-associated secretory phenotype (SASP), a broad repertoire of cytokines, chemokines, matrix remodelling proteases and growth factors, senescent cells paracrinely promote proliferation and tissue deterioration8.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [8]
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
“These data establish that inhibition of STING, both in cells and in human tissue, can block the inflammatory response of senescent cells—major contributors to inflammation during ageing8.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [8]
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
“Both proliferating and post-mitotic cells (e.g., fully differentiated cells) can be induced to senescence,3,4”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [4]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies1–3, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP)4–6.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Senescent cells accumulated in different tissues of aged mice,4,40,41 which was consistent with our observation that SA-β-gal-positive cells increased in aged livers, kidneys and lungs (Supplementary information, Fig. S5a–c).”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Senescence is triggered by stressors such as telomere shortening, DNA damage, oxidative stress, and oncogenic signals5,6,7,8”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Senescent cells, which have been implicated in the etiology of aging35”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [35]
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 [4]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, most studies analyze senescent phenotypes 7–10 days after applying the senescence inducers [36, 37].”
From Unmasking Transcriptional Heterogeneity in Senescent Cells (2017) · cites this paper as [37]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“When AP was administered during wound closure, healing was delayed with similar kinetics as 4- or 18-month-old ATTAC mice without prior AP treatment, indicating that acute senescence mechanisms are preserved with aging and not influenced by constitutive clearance of senescent cells 3 .”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We and others have previously described a role of the cGAS–STING pathway in the regulation of cellular senescence—a hallmark of ageing5–8.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [8]
Experimental — accuracy not yet measuredIn the citing paper
“Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Van Deursen, 2014
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 [935]
In the citing paper
“cellular senescence, driven by telomere dysfunction, has been shown to be a causal driver of ageing and age-related pathology (van Deursen, 2014).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as van Deursen, 2014
In the citing paper
“Among these aging hallmarks, cellular senescence plays a crucial role in brain aging, neurodegeneration, and dementia 36 through the SASP, which represents a major source of inflammation. 37”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [37]
In the citing paper
“It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response.”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [52]
In the citing paper
“Many types of chemotherapy cause DNA damage (DNA strand breaks or cross linking), which can, if severe, cause cell death via the DNA damage response, or they may trigger a non-lethal DDR, leading to acute or chronic senescence, depending on the extent and duration of the stimulus [52].”
From Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies (2020) · cites this paper as [52]
In the citing paper
“As senescent cells accumulate during aging, causing chronic inflammation (van Deursen, 2014)”
From Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway (2017) · cites this paper as van Deursen, 2014
In the citing paper
“While the limit to the extent of proliferation of cells that have damaged DNA is considered to be a natural defense against malignancy, the accumulation of senescent cells is associated with the ageing of tissues [17, 18].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [18]
In the citing paper
“In addition, the secretion of chemoattractants including IL-8 and MIP-1 recruit immune cells to ageing tissue [18]”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [18]
In the citing paper
“Senescent cells accumulate with age throughout the body and, although playing a protective role by preventing the appearance of cancer cells, they eventually promote tissue deterioration, producing a low-grade but chronic inflammatory context and acquiring a phenotype that prevents their clearance from the tissue in which they reside [14, 114].”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [114]
In the citing paper
“Mounting evidence from human samples and preclinical animal models shows that the excessive presence of senescent cells is a contributing cause of ageing, which is featured by a functional decline in multiple physiological systems [39,40].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [39]
In the citing paper
“Accumulation of senescent cells in tissues contributes to age-related diseases [[3], [4], [5], [6], [7]].”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [4]
In the citing paper
“Our results demonstrate that PPARα ligands selectively eliminate senescent chondrocytes via cell death through apoptosis [4].”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [4]
In the citing paper
“It is widely accepted that cellular senescence plays a crucial role in aging and age-related diseases (36).”
From Senolytic Combination of Dasatinib and Quercetin Alleviates Intestinal Senescence and Inflammation and Modulates the Gut Microbiome in Aged Mice (2021) · cites this paper as [36]
In the citing paper
“One major hallmark of aging is the chronic accumulation of cellular senescence, a permanent state of cell-cycle arrest in response to various damaging stimuli.3,4”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [4]
In the citing paper
“Senescent cells accumulate with age [23, 157, 175], neurodegenerative disease and cognitive decline [15], neuropsychiatric disorders [33], and have recently been discovered to accumulate after TBI [3, 123, 131, 132, 151].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [157]
In the citing paper
“Senescent MEFs remain viable (Fig. S1B) and can be metabolically active in culture for many months [2].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [2]
In the citing paper
“Activation of the senescence programme leads to cellular and molecular changes such as proliferation arrest, chromatin remodelling, elevated expression of cell cycle inhibitors (such as p16INK4A or p21CIP1), activation of a DNA damage response, enlargement of the lysosomal compartment, and activation of a senescence-associated secretory phenotype (SASP).5,6”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
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
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
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
Oxidative stress shortens telomeres
von Zglinicki, T. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(02)02110-2 · Cited by 2,524
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287
Cited by
Sorted by citations
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
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690
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
“All studies described using ATTAC mice were performed on transgenic line 3, which contains 13 copies of the transgene inserted into a single locus (data available upon request).”
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
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
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309
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
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
Senescence in Health and Disease
He, S., & Sharpless, N. E. (2017) · Cell · doi:10.1016/j.cell.2017.05.015 · Cited by 1,766
Mechanisms 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
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
Jeon, 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
Autophagy 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
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Humphreys, B. D. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034227 · Cited by 1,263
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232
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
“Interestingly, despite the immediate activation of multiple stress pathways, the emergence of the SASP is considered as a relatively late event in the development of senescence – usually requiring multiple days to arise 45.”
Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure
Gellersen, B., & Brosens, J. J. (2014) · Endocrine Reviews · doi:10.1210/er.2014-1045 · Cited by 1,176
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
cGAS–STING drives ageing-related inflammation and neurodegeneration
Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V. V., Favre, L., Mangeat, B., Kroese, L. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06373-1 · Cited by 1,104
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059
Oxidative Stress in Aging Human Skin
Rinnerthaler, M., Bischof, J., Streubel, M., Trost, A., & Richter, K. (2015) · Biomolecules · doi:10.3390/biom5020545 · Cited by 1,053
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,082
Reactive Oxygen Species: Drivers of Physiological and Pathological Processes
Checa, J., & Aran, J. M. (2020) · Journal of Inflammation Research · doi:10.2147/jir.s275595 · Cited by 1,068
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
“However, most studies analyze senescent phenotypes 7–10 days after applying the senescence inducers [36, 37].”
BackgroundAn aged immune system drives senescence and ageing of solid organs
Yousefzadeh, M. J., Flores, R. R., Zhu, Y., Schmiechen, Z. C., Brooks, R. W., Trussoni, C. E., Cui, Y., Angelini, L., Lee, K.-A., McGowan, S. J., et al. (2021) · Nature · doi:10.1038/s41586-021-03547-7 · Cited by 972
Epigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956
Senescence and apoptosis: dueling or complementary cell fates?
Childs, B. G., Baker, D. J., Kirkland, J. L., Campisi, J., & van Deursen, J. M. (2014) · The EMBO Reports · doi:10.15252/embr.201439245 · Cited by 915
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Mechanisms and therapeutic implications of cellular senescence in osteoarthritis
Coryell, P. R., Diekman, B. O., & Loeser, R. F. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-00533-7 · Cited by 761
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
Aging and age‐related diseases: from mechanisms to therapeutic strategies
Li, Z., Zhang, Z., Ren, Y., Wang, Y., Fang, J., Yue, H., Ma, S., & Guan, F. (2021) · Biogerontology · doi:10.1007/s10522-021-09910-5 · Cited by 702
The effects of aging in the hippocampus and cognitive decline
Bettio, L. E. B., Rajendran, L., & Gil‐Mohapel, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.030 · Cited by 700
Role of p53 in the Regulation of Cellular Senescence
Mijit, M., Caracciolo, V., Melillo, A., Amicarelli, F., & Giordano, A. (2020) · Biomolecules · doi:10.3390/biom10030420 · Cited by 639
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
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630
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
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
Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases
Barnes, P. J., Baker, J. R., & Donnelly, L. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201810-1975tr · Cited by 571
Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition
Pereira, B. I., Devine, O. P., Vukmanovic-Stejic, M., Chambers, E. S., Subramanian, P., Patel, N., Virasami, A., Sebire, N. J., Kinsler, V., Valdovinos, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10335-5 · Cited by 556
Mitochondria as playmakers of apoptosis, autophagy and senescence
Abate, M., Festa, A., Falco, M., Lombardi, A., Luce, A., Grimaldi, A., Zappavigna, S., Sperlongano, P., Irace, C., Caraglia, M., et al. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.022 · Cited by 552
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
Chinta, 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
Inflammation and immunity in IPF pathogenesis and treatment
Heukels, P., Moor, C. C., von der Thüsen, J. H., Wijsenbeek, M. S., & Kool, M. (2019) · Respiratory Medicine · doi:10.1016/j.rmed.2018.12.015 · Cited by 549
Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration
Wang, F., Cai, F., Shi, R., Wang, X.-H., & Wu, X. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.09.019 · Cited by 528
Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives
Baker, D. J., & Petersen, R. C. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95145 · Cited by 514
Calder, P. C., Bosco, N., Bourdet‐Sicard, R., Capuron, L., Delzenne, N. M., Dore, J. M., Franceschi, C., Lehtinen, M. J., Recker, T., Salvioli, S., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.09.001 · Cited by 524
Chung, H. Y., Kim, D. H., Lee, E. K., Chung, K. W., Chung, S., Lee, B., Seo, A. Y., Chung, J. H., Jung, Y. S., Im, E., et al. (2018) · Aging and Disease · doi:10.14336/ad.2018.0324 · Cited by 512
Renal Aging: Causes and Consequences
O’Sullivan, E. D., Hughes, J., & Ferenbach, D. A. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121308 · Cited by 484
The quest to slow ageing through drug discovery
Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0067-7 · Cited by 468
Van Meter, M., Kashyap, M., Rezazadeh, S., Geneva, A. J., Morello, T. D., Seluanov, A., & Gorbunova, V. (2014) · Nature Communications · doi:10.1038/ncomms6011 · Cited by 456
“Senescent cells, which have been implicated in the etiology of aging 35 , exhibited a 3.1 fold increase in L1 mRNA levels (Fig.”
InfluentialMasaldan, S., Clatworthy, S. A. S., Gamell, C., Meggyesy, P. M., Rigopoulos, A.-T., Haupt, S., Haupt, Y., Denoyer, D., Adlard, P. A., Bush, A. I., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2017.08.015 · Cited by 452
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 450
Focus on the Contribution of Oxidative Stress in Skin Aging
Papaccio, F., D’Arino, A., Caputo, S., & Bellei, B. (2022) · Antioxidants · doi:10.3390/antiox11061121 · Cited by 452
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424
Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity
Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L. (2015) · Diabetes · doi:10.2337/db14-1820 · Cited by 423
Stem cell competition orchestrates skin homeostasis and ageing
Liu, N., Matsumura, H., Kato, T., Ichinose, S., Takada, A., Namiki, T., Asakawa, K., Morinaga, H., Mohri, Y., De Arcangelis, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1085-7 · Cited by 422
Shahmirzadi, A. A., Edgar, D., Liao, C., Hsu, Y.-M., Lucanic, M., Shahmirzadi, A. A., Wiley, C. D., Gan, G., Kim, D. E., Kasler, H. G., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.08.004 · Cited by 429
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
“Accordingly, disruption of senescence regulators can promote cancer or impair wound healing, and the elimination of senescent cells from tissues can enhance lifespan in mice (17, 18).”
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413
Telomeres and cell senescence—size matters not
Victorelli, S., & Passos, J. F. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.03.027 · Cited by 413
Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19
Cervia, C., Nilsson, J., Zurbuchen, Y., Valaperti, A., Schreiner, J., Wolfensberger, A., Raeber, M. E., Adamo, S., Weigang, S., Emmenegger, M., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.10.040 · Cited by 411
The 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
A multidimensional systems biology analysis of cellular senescence in aging and disease
Avelar, R. A., Ortega, J. G., Tacutu, R., Tyler, E. J., Bennett, D., Binetti, P., Budovsky, A., Chatsirisupachai, K., Johnson, E., Murray, A., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-01990-9 · Cited by 399
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
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 402
Recurrent turnover of senescent cells during regeneration of a complex structure
Yun, M. H., Davaapil, H., & Brockes, J. P. (2015) · eLife · doi:10.7554/elife.05505 · Cited by 385
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
Molecular mechanisms of biological aging in intervertebral discs
Vo, N. V., Hartman, R. A., Patil, P. R., Risbud, M. V., Kletsas, D., Iatridis, J. C., Hoyland, J. A., Maitre, C. L. L., Sowa, G., & Kang, J. D. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23195 · Cited by 386
Tissue homeostasis and inflammation
Meizlish, M. L., Franklin, R. A., Zhou, X., & Medzhitov, R. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053734 · Cited by 364
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
Vizioli, M. G., Liu, T., Miller, K. N., Robertson, N. A., Gilroy, K., Lagnado, A. B., Perez-Garcia, A., Kiourtis, C., Dasgupta, N., Lei, X., et al. (2020) · Genes & Development · doi:10.1101/gad.331272.119 · Cited by 359
The integration of inflammaging in age-related diseases
Fülöp, T., Witkowski, J. M., Olivieri, F., & Larbi, A. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2018.09.003 · Cited by 368
Senescent cells and osteoarthritis: a painful connection
Jeon, O. H., David, N. E., Campisi, J., & Elisseeff, J. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95147 · Cited by 359
Hallmarks of senescence and aging
Dodig, S., Čepelak, I., & Pavić, I. (2019) · Biochemia Medica · doi:10.11613/bm.2019.030501 · Cited by 373
Role of immune cells in the removal of deleterious senescent cells
Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00187-9 · Cited by 351
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351
Ogrodnik, M. (2021) · Aging Cell · doi:10.1111/acel.13338 · Cited by 349
Cellular senescence in renal ageing and disease
Sturmlechner, I., Durik, M., Sieben, C. J., Baker, D. J., & van Deursen, J. M. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.183 · Cited by 345
Manufacturing of primed mesenchymal stromal cells for therapy
Yin, J. Q., Zhu, J., & Ankrum, J. A. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0325-8 · Cited by 349
Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice
Yousefzadeh, M. J., Zhao, J., Bukata, C., Wade, E. A., McGowan, S. J., Angelini, L. A., Bank, M. P., Gurkar, A. U., McGuckian, C. A., Calubag, M. F., et al. (2020) · Aging Cell · doi:10.1111/acel.13094 · Cited by 331
Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging
Paul, B. D., Snyder, S. H., & Bohr, V. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.008 · Cited by 336
Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium
Brighton, P. J., Maruyama, Y., Fishwick, K., Vrljicak, P., Tewary, S., Fujihara, R., Muter, J., Lucas, E. S., Yamada, T., Woods, L., et al. (2017) · eLife · doi:10.7554/elife.31274 · Cited by 323
Molecular and biological hallmarks of ageing
Aunan, J. R., Watson, M. M., Hagland, H. R., & Søreide, K. (2016) · British journal of surgery · doi:10.1002/bjs.10053 · Cited by 341
The role of cellular senescence in cardiac disease: basic biology and clinical relevance
Mehdizadeh, M., Aguilar, M., Thorin, E., Ferbeyre, G., & Nattel, S. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00624-2 · Cited by 304
New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary
Schmauck-Medina, T., Molière, A., Lautrup, S., Zhang, J., Chlopicki, S., Madsen, H. B., Cao, S., Soendenbroe, C., Mansell, E., Vestergaard, M. B., et al. (2022) · Aging · doi:10.18632/aging.204248 · Cited by 319
Orr, M., Gonzales, M., Garbarino, V., Kautz, T., Palavicini, J., Lopez-Cruzan, M., Dehkordi, S. K., Mathews, J., Zare, H., Xu, P., et al. (2023) · doi:10.21203/rs.3.rs-2809973/v1 · Cited by 319
Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial
Gonzales, M. M., Garbarino, V. R., Kautz, T. F., Palavicini, J. P., Lopez-Cruzan, M., Dehkordi, S. K., Mathews, J. J., Zare, H., Xu, P., Zhang, B., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02543-w · Cited by 334
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 323
Cellular senescence in brain aging
Sikora, E., Bielak-Zmijewska, A., Dudkowska, M., Krzystyniak, A., Mosieniak, G., Wesierska, M., & Wlodarczyk, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.646924 · Cited by 304
“Moreover, accumulation of senescent cells have been observed in age and they are the culprit of many age-related diseases (van Deursen, 2014).”
BackgroundÖzcan, S., Alessio, N., Acar, M. B., Mert, E., Omerli, F., Peluso, G., & Galderisi, U. (2016) · Aging · doi:10.18632/aging.100971 · Cited by 295
p21 produces a bioactive secretome that places stressed cells under immunosurveillance
Sturmlechner, I., Zhang, C., Sine, C. C., van Deursen, E.-J., Jeganathan, K. B., Hamada, N., Grasic, J., Friedman, D., Stutchman, J. T., Can, I., et al. (2021) · Science · doi:10.1126/science.abb3420 · Cited by 295
“Cells that fail to recuperate—for instance, because of severe or prolonged stresses—engage programs that execute regulated cell death or cellular senescence, thereby limiting the risk of neoplastic transformation (2, 3).”
BackgroundCellular Senescence in the Kidney
Docherty, M.-H., O’Sullivan, E. D., Bonventre, J. V., & Ferenbach, D. A. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121251 · Cited by 291
Franceschi, C., Salvioli, S., Garagnani, P., de Eguileor, M., Monti, D., & Capri, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00982 · Cited by 290
Targeting senescent cells in translational medicine
Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
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
Metadata
- Authors
- van Deursen, J. M.
- Venue
- Nature
- Published
- 2014-05-21
- Volume
- 509
- Issue
- 7501
- Pages
- 439-446
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4214092
- OpenAlex
- W2130458932
- Cited by
- 2,623
- References
- 99
- Citations by year
- 2026: 160 · 2025: 217 · 2024: 251 · 2023: 295 · 2022: 285 · 2021: 364 · 2020: 272 · 2019: 203 · 2018: 195 · 2017: 132 · 2016: 140 · 2015: 83 · 2014: 24
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Foundation for the National Institutes of Health
- Glenn Foundation for Medical Research
- National Institute on Aging (AG41122-01P2, P01AG041122)
- National Cancer Institute (R01CA166347, R01CA096985, R01CA96985)
- 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, aging, senolytics, age-related diseases, tissue repair, cancer prevention, growth arrest, healthspan, senolytic therapy
- MeSH terms
- Aging, Animals, Disease, Humans, Longevity, Mitosis, 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
