Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Open accessAbstract
Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions.
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?
The paper states that p16 is a key trigger of cellular senescence and has been proposed as a biomarker of mammalian aging.
“p16 is a key trigger of cellular senescence16, and its expression increases with aging in several rodent and primate tissues17–19, suggesting its potential use as a biomarker of mammalian aging.”
From Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial (2024) · cites this paper as [16]
The Cellular senescence section (page unavailable) says that senescence-inducing insults activate the p16INK4a pathway, which helps initiate a senescence response. The References section (page unavailable) lists work describing Ink4a/Arf expression as a biomarker of aging. The paper does not itself establish the more specific claim that p16 expression rises with age across several rodent and primate tissues; it also describes p16 as a pathway activated by triggers, rather than as the trigger itself. (LLM, conf=0.82)
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 [64]
The SASP and Figure 2 passages describe inflammatory SASP factors and suggest that senescence can spread to neighboring cells. They do not establish the 30–70% figure, characterize SASP factors as proapoptotic or pro-fibrotic, or show that they induce senescence at a distance through endocrine action; the paper also frames spreading senescence as a possibility needing further investigation. Page numbers were not available in our copy. (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 [64]
The Research issues section (page unavailable) proposes blood biomarkers of senescent-cell burden based on detecting SASP products. It does not establish that such assays are available, or address α-Klotho or assays in urine, saliva, or cerebrospinal fluid. Searches for those fluids and α-Klotho found no supporting passage. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCellular senescence is one fundamental aging mechanism that contributes to many age-related diseases.
“One fundamental aging mechanism that underlies numerous age-related diseases is cellular senescence (5).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [5]
The Cellular senescence section calls senescence a basic process that may contribute to age-related dysfunction and reports evidence that senescent cells drive multiple age-related pathologies. But it limits the clear experimental evidence to a progeroid mouse model and says it remains to be tested in chronologically aged models. The citing sentence states the broader role without those qualifications. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSenescent cells secrete SASP, which alters the extracellular matrix, impairs stem cell functions, promotes transdifferentiation, can spread senescence to surrounding cells, and causes systemic chronic inflammation.
“Importantly, senescent cells secrete a complex set of pro-inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). This alters the composition of the extracellular matrix, impairs stem cell functions, promotes cell transdifferentiation and can spread the senescence phenotype to surrounding cells, thereby causing systemic chronic inflammation12.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [12]
The Figure 2 passage links the SASP to extracellular-matrix degradation and says it appears to spread between cells. The SASP section says its cytokines can cause epithelial-to-mesenchymal transitions, but describes systemic inflammation as potential and context-dependent. Figure 2 attributes removal from the progenitor/stem-cell pool to senescence, not specifically to SASP-mediated impairment of stem-cell function. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Cellular senescence is associated with cardiovascular dysfunction in humans.
“Cellular senescence is associated with cardiovascular dysfunction in humans (Tchkonia et al., 2013; Kirkland & Tchkonia, 2014), a major cause of morbidity and mortality in the elderly.”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Tchkonia et al., 2013
The References section names a study of senescence in endothelial cells from patients with atherosclerosis, supporting a human cardiovascular association. The Cellular senescence section discusses age-related dysfunction more broadly, but the review does not explicitly establish an association with cardiovascular dysfunction in humans generally. No page is available for these passages in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe accumulation of senescent cells contributes to tissue and organismal aging and is a well-known aging hallmark.
“The accumulation of senescent cells contributes to tissue and organismal aging and is a well-known aging hallmark.56”
From Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging (2024) · cites this paper as [66]
The Cellular senescence section says senescent cells increase in multiple tissues with chronological aging and describes evidence that they drive age-related pathologies. But it limits the evidence from clearing senescent cells to a progeroid mouse model and says the finding remains to be tested in chronologically aged models. The claim states their contribution to tissue and organismal aging more definitively than the source does. (LLM, conf=0.85)
Experimental — accuracy not yet measuredInterventions that reduce the burden of senescent cells could ameliorate age-related disabilities and chronic diseases as a group.
“Thus, interventions that reduce the burden of senescent cells could ameliorate age-related disabilities and chronic diseases as a group (Tchkonia et al., 2013; Kirkland & Tchkonia, 2014).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Tchkonia et al., 2013
Cellular senescence likely contributes to chronic diseases and age-related dysfunction.
“A fundamental aging mechanism that likely contributes to chronic diseases and age-related dysfunction is cellular senescence (Kirkland, 2013b,a; Tchkonia et al., 2013; Kirkland & Tchkonia, 2014).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Tchkonia et al., 2013
As senescent cells do not divide, drug resistance would be expected to be less likely than with antibiotics or cancer treatment, in which cells proliferate and can acquire resistance.
“as senescent cells do not divide, drug resistance would be expected to be less likely than is the case with antibiotics or cancer treatment, in which cells proliferate and so can acquire resistance”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Tchkonia et al., 2013
Senescent cells have been identified at sites of pathology in multiple diseases and disabilities or may have systemic effects that predispose to others.
“Senescent cells have been identified at sites of pathology in multiple diseases and disabilities or may have systemic effects that predispose to others (Tchkonia et al., 2013; Kirkland & Tchkonia, 2014).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Tchkonia et al., 2013
Senescent cells can initiate a deleterious positive feedback mechanism by promoting the spread of senescence to nearby cells.
“Senescent cells can also initiate a deleterious positive feedback mechanism by promoting the spread of senescence to nearby cells (17–19).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [18]
Senescent cells express and secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, a set collectively called the senescence-associated secretory phenotype (SASP).
“senescent cells display extensive changes in gene expression, including the expression and secretion of many proinflammatory cytokines, chemokines, growth factors, and proteases; collectively these features are termed the senescence-associated secretory phenotype (SASP) (2, 7–10).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [10]
The SASP does not depend on p53 or p16INK4a, suggesting that it is controlled by a separate branch of the senescence regulatory network.
“the SASP does not depend on either p53 or p16INK4a, which suggests that it is controlled by an independent branch of the senescence regulatory network (2, 10, 20, 26).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [10]
Factors secreted by senescent cells may promote chronic inflammation, which is thought to be a major factor in many age-related diseases.
“factors secreted by senescent cells may directly or indirectly promote chronic inflammation that is thought to be a major factor in many, if not all, age-related diseases (2, 9, 10).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [10]
Accumulation of senescent cells as organisms age is thought to promote aging-related phenotypes and diseases, including cancer and neurodegeneration, in a cell-nonautonomous manner.
“the accumulation of senescent cells as organisms age is thought to promote aging-related phenotypes and aging-associated diseases, including cancer and neurodegeneration, in a cell-nonautonomous manner (2, 3, 10).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [10]
These inflammatory cytokines promote senescence locally in a paracrine manner and perhaps at a systemic level.
“These inflammatory cytokines promote senescence locally in a paracrine manner30 and perhaps, at a systemic level.111”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [111]
Activation of the p38 pathway is directly involved in loss of telomerase activity and proliferative capacity, as well as increased production of inflammatory cytokines similar to the senescence-associated secretory phenotype in fibroblasts.
“Activation of the p38 pathway is directly involved in the loss of telomerase activity and of proliferative capacity, as well as the increased production of inflammatory cytokines similar to the senescence-associated secretory phenotype in fibroblasts”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Tchkonia et al., 2013
The senescence associated secretory phenotype is considered important for remodelling of ageing tissues.
“This is known as the senescence associated secretory phenotype or SASP and is considered to be important for remodelling of ageing tissues [41, 42].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [42]
Cellular senescence can cause chronic inflammation through the SASP, and this chronic non-microbial sterile inflammation is thought to be the prime cause of many age-related disorders such as atherosclerosis, autoimmunity, cancers and dementias.
“Cellular senescence can cause chronic inflammation through the SASP and this chronic nonmicrobial (sterile) inflammation is thought to be the prime cause of many age-related disorders such as atherosclerosis, autoimmunity, cancers and dementias [42].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [42]
Cellular senescence is marked by permanent cell-cycle arrest, altered gene expression, activation of tumour suppression, chromatin changes, apoptosis resistance, and higher protein synthesis.
“Cellular senescence is characterized by an irreversible cell cycle arrest, changes in gene expression, tumour suppression activation, altered chromatin, resistance to apoptosis and increased protein synthesis89.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [89]
The accumulation of senescent cells during aging is implicated as a causal factor in aging-associated inflammation and disruptions of ECM.
“Because of this the accumulation of senescent cells during aging is implicated as a causal factor in aging-associated inflammation and disruptions of ECM.”
From Programmed cell death in aging (2015) · cites this paper as Tchkonia et al., 2013
The composition and intensity of the SASP response can be affected by the senescence-inducing mechanism, cell type, and time since senescence initiation, indicating that there is no singular SASP.
“The composition and intensity of the SASP response can be affected by several factors including the senescence-inducing mechanism, cell type, and the amount of time passed since senescence initiation, indicating that there is no singular SASP.12–17”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [17]
Dysregulation or inappropriate activation of senescence contributes to tumour progression and malignancy.
“There is mounting evidence that dysregulation or inappropriate activation of senescence contributes to tumour progression and malignancy.5,7,17”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [17]
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
Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Self-citationC-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Self-citationAssociations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.
Howren, M. B., Lamkin, D. M., & Suls, J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181907c1b · Cited by 2,766 · see citing works
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 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
Self-citationPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Self-citationFranceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · see citing works
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038 · see citing works
Senescence of activated stellate cells limits liver fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.06.049 · Cited by 2,029 · see citing works
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · cited 2× · see citing works
“The SASP can cause local and potentially systemic inflammation, disrupt tissue architecture, and stimulate growth of nearby malignant cells when the SASP is both pronounced or persistent, as in old age, massive obesity, or pro-gerias (65, 84–88).”
Self-citationChemokine 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
“The SASP cytokines, IL-6 and IL-8, also reinforce the senescence growth arrest, at least in some senescent cells (62, 63), which is beneficial in defense against cancer.”
Kirkwood, T. B. L., & Austad, S. N. (2000) · Nature · doi:10.1038/35041682 · Cited by 1,774 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621 · see citing works
Walston, J., Hadley, E. C., Ferrucci, L., Guralnik, J. M., Newman, A. B., Studenski, S. A., Ershler, W. B., Harris, T., & Fried, L. P. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00745.x · Cited by 1,605 · see citing works
Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes
Spranger, J., Kroke, A., Möhlig, M., Hoffmann, K., Bergmann, M. M., Ristow, M., Boeing, H., & Pfeiffer, A. F. H. (2003) · Diabetes · doi:10.2337/diabetes.52.3.812 · Cited by 1,493 · see citing works
Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly
Harris, T. B., Ferrucci, L., Tracy, R. P., Corti, M. C., Wacholder, S., Ettinger, W. H., Heimovitz, H., Cohen, H. J., & Wallace, R. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00066-2 · Cited by 1,488 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Inflammatory networks during cellular senescence: causes and consequences.
Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.003 · Cited by 1,354 · see citing works
Self-citationThe DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
Gasser, S., Orsulic, S., Brown, E. J., & Raulet, D. H. (2005) · Nature · doi:10.1038/nature03884 · Cited by 1,308 · see citing works
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220 · see citing works
Phenotype of frailty: characterization in the women's health and aging studies
Bandeen-Roche, K., Xue, Q.-L., Ferrucci, L., Walston, J., Guralnik, J. M., Chaves, P., Zeger, S. L., & Fried, L. P. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.3.262 · Cited by 1,215 · see citing works
Molecular inflammation: Underpinnings of aging and age-related diseases
Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., Carter, C., Yu, B. P., & Leeuwenburgh, C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2008.07.002 · Cited by 1,203 · see citing works
Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women
Pai, J. K., Pischon, T., Ma, J., Manson, J. E., Hankinson, S. E., JOSHIPURA, K. J., Curhan, G. C., Rifai, N., Cannuscio, C. C., Stampfer, M. J., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040967 · Cited by 1,174 · see citing works
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101 · see citing works
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · 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
“61–64 , 92– 94 ).”
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 process is reinforced by an intracellular signaling loop including ROS linked to DNA damage responses (DDRs), NF κ B, and transforming growth factor-β , as well as an IL-1 α , IL-6, and CCAAT enhancer binding protein-β (C/EBP-β ) loop (59, 61–64).”
Frailty Defined by Deficit Accumulation and Geriatric Medicine Defined by Frailty
Rockwood, K. J., & Mitnitski, A. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.008 · Cited by 1,001 · see citing works
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · see citing works
Walston, J. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.20.2333 · Cited by 940 · see citing works
Cellular senescence as a tumor-suppressor mechanism
Campisi, J. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02151-1 · Cited by 936 · see citing works
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
Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis
Sparmann, A., & Bar‐Sagi, D. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.028 · Cited by 854 · see citing works
Serum IL‐6 Level and the Development of Disability in Older Persons
Ferrucci, L., Harris, T. B., Guralnik, J. M., Tracy, R. P., Corti, M., Cohen, H. J., Penninx, B., Pahor, M., Wallace, R., & Havlik, R. J. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb01583.x · Cited by 809 · see citing works
Inflammatory Markers and Risk of Developing Type 2 Diabetes in Women
Hu, F. B., Meigs, J. B., Li, T. Y., Rifai, N., & Manson, J. E. (2004) · Diabetes · doi:10.2337/diabetes.53.3.693 · Cited by 788 · see citing works
A senescent cell bystander effect: senescence‐induced senescence
Nelson, G., Wordsworth, J., Wang, C., Jurk, D., Lawless, C., Martin‐Ruiz, C., & von Zglinicki, T. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00795.x · Cited by 755 · see citing works
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Naugler, W. E., & Karin, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.007 · Cited by 730 · see citing works
With TOR, Less Is More: A Key Role for the Conserved Nutrient-Sensing TOR Pathway in Aging
Kapahi, P., Chen, D., Rogers, A. N., Katewa, S. D., Li, P. W.-L., Thomas, E., & Kockel, L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.001 · Cited by 663 · see citing works
Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways
Schetter, A. J., Heegaard, N. H. H., & Harris, C. C. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp272 · Cited by 659 · see citing works
Orjalo, 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
Self-citationIn Search of Methuselah: Estimating the Upper Limits to Human Longevity
Olshansky, S. J., Carnes, B. A., & Cassel, C. (1990) · Science · doi:10.1126/science.2237414 · Cited by 645 · see citing works
Parrinello, S., Coppe, J.-P., Krtolica, A., & Campisi, J. (2005) · Journal of Cell Science · doi:10.1242/jcs.01635 · Cited by 631 · see citing works
Self-citationAge-related inflammatory cytokines and disease
Brüünsgaard, H., & Pedersen, B. K. (2003) · Immunology and Allergy Clinics of North America · doi:10.1016/s0889-8561(02)00056-5 · Cited by 608 · see citing works
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571 · see citing works
Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice
Krimpenfort, P., Quon, K. C., Mooi, W. J., Loonstra, A., & Berns, A. (2001) · Nature · doi:10.1038/35092584 · Cited by 568 · see citing works
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553 · see citing works
Self-citationFried, L. P., Xue, Q.-L., Cappola, A. R., Ferrucci, L., Chaves, P., Varadhan, R., Guralnik, J. M., Leng, S. X., Semba, R. D., Walston, J. D., et al. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp076 · Cited by 539 · see citing works
Guerra, C., Collado, M., Navas, C., Schuhmacher, A. J., Hernández-Porras, I., Cañamero, M., Rodriguez-Justo, M., Serrano, M., & Barbacid, M. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.05.011 · Cited by 516 · see citing works
Coppé, J.-P., Rodier, F., Patil, C. K., Freund, A., Desprez, P.-Y., & Campisi, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257071 · Cited by 506 · 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
Self-citationLiu, D., & Hornsby, P. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3452 · Cited by 499 · see citing works
Rockwood, K., Mitnitski, A., Song, X., Steen, B., & Skoog, I. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00738.x · Cited by 481 · see citing works
Inflammatory networks in ageing, age-related diseases and longevity
Vasto, S., Candore, G., Balistreri, C. R., Caruso, M., Colonna‐Romano, G., Grimaldi, M. P., Listı̀, F., Nuzzo, D., Lio, D., & Caruso, C. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.015 · Cited by 481 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P.-Y., & Campisi, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009188 · Cited by 455 · see citing works
Self-citationInflammation and frailty in older women
Leng, S. X., Xue, Q., Tian, J., Walston, J. D., & Fried, L. P. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01186.x · Cited by 425 · see citing works
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
Ancrile, B., Lim, K.-H., & Counter, C. M. (2007) · Genes & Development · doi:10.1101/gad.1549407 · Cited by 422 · see citing works
Cellular senescence: a link between cancer and age-related degenerative disease?
Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.09.001 · Cited by 421 · see citing works
Self-citationOpposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency
Baker, D. J., Perez-Terzic, C., Jin, F., Pitel, K. S., Niederländer, N. J., Jeganathan, K., Yamada, S., Reyes, S., Rowe, L., Hiddinga, H. J., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1744 · Cited by 408 · cited 1× · see citing works
“The abundance of senescent cells increases in multiple tissues with chronological aging and in progeroid syndromes (43, 47, 50, 52–55).”
Many roads lead to oncogene-induced senescence
Courtois-Cox, S., Jones, S. L., & Cichowski, K. (2008) · Oncogene · doi:10.1038/sj.onc.1210950 · Cited by 397 · see citing works
The role of chondrocyte senescence in osteoarthritis
Price, J. S., Waters, J. G., Darrah, C., Pennington, C., Edwards, D. R., Donell, S. T., & Clark, I. M. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00008.x · Cited by 386 · see citing works
Cellular senescence: putting the paradoxes in perspective
Campisi, J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.005 · Cited by 368 · see citing works
Self-citationCellular senescence and organismal aging
Jeyapalan, J. C., & Sedivy, J. M. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.04.001 · Cited by 347 · see citing works
Elevated levels of tumor necrosis factor alpha and mortality in centenarians
Bruunsgaard, H., Andersen-Ranberg, K., Hjelmborg, J. V. B., Pedersen, B. K., & Jeune, B. (2003) · The American Journal of Medicine · doi:10.1016/s0002-9343(03)00329-2 · Cited by 325 · see citing works
Leukocyte Count as a Predictor of Cardiovascular Events and Mortality in Postmenopausal Women
Margolis, K. L. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.5.500 · Cited by 310 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 2× · see citing works
“…cells from the progenitor/stem cell pool, senescence may contribute to tissue dysfunction and chronic disease predisposition through the SASP and associated chronic sterile inflammation and degradation of the extracellular matrix. including MCP-1, are prominent components of the SASP (64, 81).”
Self-citationCesari, M., Penninx, B. W. J. H., Newman, A. B., Kritchevsky, S. B., Nicklas, B. J., Sutton-Tyrrell, K., Tracy, R. P., Rubin, S. M., Harris, T. B., & Pahor, M. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00718-5 · Cited by 302 · see citing works
Weyemi, U., Lagente-Chevallier, O., Boufraqech, M., Prenois, F., Courtin, F., Caillou, B., Talbot, M., Dardalhon, M., Al Ghuzlan, A., Bidart, J.-M., et al. (2012) · Oncogene · doi:10.1038/onc.2011.327 · Cited by 285 · see citing works
Oncogene-Induced Senescence: Putting the Brakes on Tumor Development
Braig, M., & Schmitt, C. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4006 · Cited by 274 · see citing works
Srikrishna, G., & Freeze, H. H. (2009) · Neoplasia · doi:10.1593/neo.09284 · Cited by 274 · see citing works
The number of p16INK4a positive cells in human skin reflects biological age
Waaijer, M. E. C., Parish, W. E., Strongitharm, B. H., van Heemst, D., Slagboom, P. E., de Craen, A. J. M., Sedivy, J. M., Westendorp, R. G. J., Gunn, D. A., & Maier, A. B. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00837.x · Cited by 264 · see citing works
Cellular senescence in vivo: a barrier to tumorigenesis
Prieur, A., & Peeper, D. S. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.01.007 · Cited by 260 · see citing works
Cellular senescence controls fibrosis in wound healing
Jun, J.-I., & Lau, L. F. (2010) · Aging · doi:10.18632/aging.100201 · Cited by 255 · see citing works
Hoenicke, L., & Zender, L. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs124 · Cited by 248 · see citing works
Nagabhushanam, V., Solache, A., Ting, L.-M., Escaron, C. J., Zhang, J. Y., & Ernst, J. D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4750 · Cited by 247 · see citing works
Brown, D. W., Giles, W. H., & Croft, J. B. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(00)00296-1 · Cited by 241 · see citing works
Interleukin-6 Causes Endothelial Barrier Dysfunction via the Protein Kinase C Pathway
Desai, T. R., Leeper, N. J., Hynes, K. L., & Gewertz, B. L. (2002) · Journal of Surgical Research · doi:10.1006/jsre.2002.6415 · Cited by 235 · see citing works
Tuomisto, K., Jousilahti, P., Sundvall, J., Pajunen, P., & Salomaa, V. V. (2006) · Thrombosis and Haemostasis · doi:10.1160/th05-08-0571 · Cited by 231 · see citing works
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
Self-citationSuram, A., Kaplunov, J., Patel, P. L., Ruan, H., Cerutti, A., Boccardi, V., Fumagalli, M., Di Micco, R., Mirani, N., Gurung, R. L., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.132 · Cited by 227 · see citing works
Sitte, N., Merker, K., von Zglinicki, T., Grune, T., & Davies, K. J. A. (2000) · The FASEB Journal · doi:10.1096/fj.00-0209com · Cited by 213 · see citing works
Guerrero, A., Uchida, K., Nakajima, H., Watanabe, S., Nakamura, M., Johnson, W. E., & Baba, H. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-40 · Cited by 196 · see citing works
Badache, A., & Hynes, N. E. (2001) · PubMed · Cited by 189 · see citing works
What Can Progeroid Syndromes Tell Us About Human Aging?
Kipling, D., Davis, T., Ostler, E. L., & Faragher, R. (2004) · Science · doi:10.1126/science.1102587 · Cited by 182 · see citing works
Inflammation, Coagulation, and the Pathway to Frailty
Kanapuru, B., & Ershler, W. B. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.01.030 · Cited by 163 · see citing works
Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease
O’Connor, P. M. J., Lapointe, T. K., Beck, P. L., & Buret, A. G. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21217 · Cited by 151 · see citing works
Loss of Proliferative Capacity and Induction of Senescence in Oxidatively Stressed Human Fibroblasts
Chen, J., Stoeber, K., Kingsbury, S. R., Ozanne, S. E., Williams, G. H., & Hales, C. N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409153200 · Cited by 148 · see citing works
Adult-onset, short-term dietary restriction reduces cell senescence in mice
Wang, C., Maddick, M., Miwa, S., Jurk, D., Czapiewski, R., Saretzki, G., Langie, S. A. S., Godschalk, R. W. L., Cameron, K., & von Zglinicki, T. (2010) · Aging · doi:10.18632/aging.100196 · Cited by 142 · see citing works
Voghel, G., Thorin‐Trescases, N., Farhat, N., Nguyen, A. Q., Villeneuve, L. R., Mamarbachi, A. M., Fortier, A., Perrault, L. P., Carrier, M., & Thorin, É. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.09.006 · Cited by 141 · see citing works
Cellular senescence, ageing and disease
Burton, D. G. A. (2008) · AGE · doi:10.1007/s11357-008-9075-y · Cited by 135 · see citing works
Golde, T. E., & Miller, V. M. (2009) · Alzheimer's Research & Therapy · doi:10.1186/alzrt5 · Cited by 98 · see citing works
Healthspan, Translation, and New Outcomes for Animal Studies of Aging
Kirkland, J. L., & Peterson, C. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gln063 · Cited by 98 · see citing works
Self-citationBajada, S., Marshall, M. J. E., Wright, K. T., Richardson, J. B., & Johnson, W. E. B. (2009) · Bone · doi:10.1016/j.bone.2009.06.015 · Cited by 97 · see citing works
Measuring Systemic Inflammatory Regulation in Older Adults: Evidence and Utility
Bandeen-Roche, K., Walston, J. D., Huang, Y., Semba, R. D., & Ferrucci, L. (2009) · Rejuvenation Research · doi:10.1089/rej.2009.0883 · Cited by 94 · see citing works
Fülöp, T., Franceschi, C., Hirokawa, K., & Pawelec, G. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9 · Cited by 92 · see citing works
Unexpected Pieces to the Senescence Puzzle
Cichowski, K. M., & Hahn, W. C. (2008) · Cell · doi:10.1016/j.cell.2008.05.027 · Cited by 80 · see citing works
Qu, T., Walston, J. D., Yang, H., Fedarko, N. S., Xue, Q.-L., Beamer, B. A., Ferrucci, L., Rose, N. R., & Leng, S. X. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.10.005 · Cited by 61 · see citing works
Ohtani, N., Yamakoshi, K., Takahashi, A., & Hara, E. (2010) · Cell Division · doi:10.1186/1747-1028-5-1 · Cited by 61 · see citing works
Walston, J. D., Matteini, A. M., Nievergelt, C. M., Lange, L. A., Fallin, D., Barzilai, N., Ziv, E., Pawlikowska, L., Kwok, P., Cummings, S., et al. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.02.004 · Cited by 51 · see citing works
Cell-adhesion-disrupting action of interleukin 6 in human ductal breast carcinoma cells.
Tamm, I., Kikuchi, T., Cardinale, I., & Krueger, J. G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3329 · Cited by 47 · see citing works
Cecco, M. D., Jeyapalan, J. C., Zhao, X., Tamamori‐Adachi, M., & Sedivy, J. M. (2011) · Aging · doi:10.18632/aging.100372 · Cited by 47 · see citing works
Ferrucci, L., Blè, A., Bandinelli, S., Lauretani, F., Suthers, K., & Guralnik, J. M. (2004) · Aging Clinical and Experimental Research · doi:10.1007/bf03327390 · Cited by 39 · see citing works
New insights into oncogenic stress
Haigis, K. M., & Sweet-Cordero, A. (2011) · Nature Genetics · doi:10.1038/ng0311-177 · Cited by 36 · see citing works
An index of self-rated health deficits in relation to frailty and adverse outcomes in older adults
Lucicesare, A., Hubbard, R. E., Searle, S. D., & Rockwood, K. J. (2010) · Aging Clinical and Experimental Research · doi:10.1007/bf03324805 · Cited by 35 · see citing works
Książek, K., Mikuła-Pietrasik, J., Olijslagers, S. J., Jörres, A., von Zglinicki, T., & Witowski, J. (2009) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.90451.2008 · Cited by 33 · see citing works
Molecular and Cellular Aspects of Macrophage Aging
Sebastián, C., Lloberas, J., & Celada, A. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_46 · Cited by 24 · see citing works
Yevsa, T., Kang, T.-W., & Zender, L. (2012) · OncoImmunology · doi:10.4161/onci.19128 · Cited by 24 · see citing works
Kipling, D., Jones, D. L., Smith, S. K., Giles, P. J., Jennert-Burston, K., Ibrahim, B., Sheerin, A. N. P., Evans, A. J. C., Rhys-Willams, W., & Faragher, R. G. A. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2008.11.030 · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [64]64. Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev. 2010;24(22):2463-2479.
Cited by
Sorted by citations
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · see citing works
Self-citationThe role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Self-citationThe Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,562 · see citing works
“examined in animalmodels of other conditionsor diseases towhich cellular senescence may contribute to pathogenesis, including diabetes, neurodegenerative disorders, osteoarthritis, chronic pulmonary disease, renal diseases, and others (Tchkonia et al., 2013; Kirkland & Tchkonia, 2014).”
BackgroundInfluentialSelf-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-citationClearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · see citing works
Self-citationSarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797 · see citing works
Self-citationA proteomic atlas of senescence-associated secretomes for aging biomarker development
Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., Ferrucci, L., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000599 · Cited by 1,348 · see citing works
Self-citationThe twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · 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 · see citing works
“A prominent hallmark of senescent cells is the secretion of inflammatory mediators, including various cytokines, chemokines, extracellular matrix proteins and growth factors, collectively referred to as the senescence-associated secretory phenotype (SASP)3 4.”
Targeting cellular senescence prevents age-related bone loss in mice
Farr, J. N., Xu, M., Weivoda, M. M., Monroe, D. G., Fraser, D. G., Onken, J. L., Negley, B. A., Sfeir, J. G., Ogrodnik, M. B., Hachfeld, C. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4385 · Cited by 1,182 · see citing works
Self-citationZhu, 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 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-citationA new gene set identifies senescent cells and predicts senescence-associated pathways across tissues
Saul, D., Kosinsky, R. L., Atkinson, E. J., Doolittle, M. L., Zhang, X., LeBrasseur, N. K., Pignolo, R. J., Robbins, P. D., Niedernhofer, L. J., Ikeno, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32552-1 · Cited by 1,060 · see citing works
Self-citationFisetin 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-citationCellular senescence: a translational perspective
Kirkland, J. L., & Tchkonia, T. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.013 · Cited by 1,013 · see citing works
Self-citationThe DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Kang, C., Xu, Q., Martin, T. D., Li, M. Z., Demaria, M., Aron, L., Lu, T., Yankner, B. A., Campisi, J., & Elledge, S. J. (2015) · Science · doi:10.1126/science.aaa5612 · Cited by 982 · see citing works
Self-citationThe Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates
Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., & Salvioli, S. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00061 · Cited by 945 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · 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 · see citing works
Self-citationChronic inflammation induces telomere dysfunction and accelerates ageing in mice
Jurk, D., Wilson, C., Passos, J. F., Oakley, F., Correia-Melo, C., Greaves, L., Saretzki, G., Fox, C., Lawless, C., Anderson, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms5172 · Cited by 814 · see citing works
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 · see citing works
Mitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796 · see citing works
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788 · see citing works
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 · see citing works
Identification of HSP90 inhibitors as a novel class of senolytics
Fuhrmann-Stroissnigg, H., Ling, Y. Y., Zhao, J., McGowan, S. J., Zhu, Y., Brooks, R. W., Grassi, D., Gregg, S. Q., Stripay, J. L., Dorronsoro, A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00314-z · Cited by 701 · see citing works
Self-citationRole of Telomeres and Telomerase in Aging and Cancer
Shay, J. W. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0062 · Cited by 668 · see citing works
The Role of Inflammation in Age-Related Sarcopenia
Dalle, S., Rossmeislova, L., & Koppo, K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.01045 · Cited by 668 · see citing works
Age and immunity: What is “immunosenescence”?
Pawelec, G. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.024 · Cited by 606 · see citing works
Interventions to slow aging in humans: are we ready?
Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., Curiel, T. J., Cabo, R., Franceschi, C., Gems, D., et al. (2015) · Aging Cell · doi:10.1111/acel.12338 · Cited by 592 · 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-citationVascular smooth muscle cell death, autophagy and senescence in atherosclerosis
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy007 · Cited by 606 · see citing works
Identification of senescent cells in the bone microenvironment
Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2892 · Cited by 562 · see citing works
Self-citationObesity-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-citationThe Clinical potential of Senolytic Drugs
Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14969 · Cited by 539 · see citing works
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-citationMechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506 · see citing works
Strategies for targeting senescent cells in human disease
Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021) · Nature Aging · doi:10.1038/s43587-021-00121-8 · Cited by 501 · see citing works
Self-citationSenescent 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-citationAdvances in pathogenesis and therapeutic strategies for osteoporosis
Song, S., Guo, Y., Yang, Y., & Fu, D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108168 · Cited by 476 · see citing works
Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes
Aguayo-Mazzucato, C., Andle, J., Lee, T. B., Midha, A., Talemal, L., Chipashvili, V., Hollister-Lock, J., van Deursen, J., Weir, G., & Bonner-Weir, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.006 · Cited by 469 · see citing works
Self-citationContributions 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 · see citing works
Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan
Grosse, L., Wagner, N., Emelyanov, A., Molina, C., Lacas-Gervais, S., Wagner, K.-D., & Bulavin, D. V. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.05.002 · Cited by 460 · see citing works
Immunology of aging: the birth of inflammaging
Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A. A., Hirokawa, K., Witkowski, J. M., & Franceschi, C. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08899-6 · Cited by 464 · see citing works
Programmed cell death in aging
Tower, J. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.04.002 · Cited by 426 · see citing works
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 · see citing works
Self-citationSource 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 · see citing works
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 · see citing works
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362 · see citing works
Parainflammation, Chronic Inflammation and Age-Related Macular Degeneration
Chen, M., & Xu, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0615-239r · Cited by 381 · see citing works
Inflammaging decreases adaptive and innate immune responses in mice and humans
Frasca, D., & Blomberg, B. B. (2016) · Biogerontology · doi:10.1007/s10522-015-9578-8 · Cited by 357 · see citing works
Cardiac glycosides are broad-spectrum senolytics
Guerrero, A., Herranz, N., Sun, B., Wagner, V., Gallage, S., Guiho, R., Wolter, K., Pombo, J., Irvine, E. E., Innes, A. J., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0122-z · Cited by 359 · see citing works
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I., et al. (2016) · Aging · doi:10.18632/aging.100991 · Cited by 357 · see citing works
Tumour burden and efficacy of immune-checkpoint inhibitors
Dall’Olio, F. G., Marabelle, A., Caramella, C., Garcia, C., Aldea, M., Chaput, N., Robert, C., & Besse, B. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00564-3 · Cited by 350 · see citing works
Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes
Thompson, P. J., Shah, A., Ntranos, V., Van Gool, F., Atkinson, M., & Bhushan, A. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.021 · Cited by 353 · see citing works
Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice
Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., Curran, G. L., Ogrodnik, M., Jurk, D., Johnson, K. O., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw154 · Cited by 352 · see citing works
Self-citationShared molecular and cellular mechanisms of premature ageing and ageing-associated diseases
Kubben, N., & Misteli, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.68 · Cited by 320 · see citing works
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 · see citing works
Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
Robbins, P. D., Jurk, D., Khosla, S., Kirkland, J. L., LeBrasseur, N. K., Miller, J. D., Passos, J. F., Pignolo, R. J., Tchkonia, T., & Niedernhofer, L. J. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-050120-105018 · Cited by 339 · see citing works
Self-citationYang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J., & Weyand, C. M. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130252 · Cited by 334 · see citing works
Arai, Y., Martin-Ruiz, C. M., Takayama, M., Abe, Y., Takebayashi, T., Koyasu, S., Suematsu, M., Hirose, N., & von Zglinicki, T. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.07.029 · Cited by 333 · see citing works
Cellular senescence: at the nexus between ageing and diabetes
Palmer, A. K., Gustafson, B., Kirkland, J. L., & Smith, U. (2019) · Diabetologia · doi:10.1007/s00125-019-4934-x · Cited by 337 · see citing works
Self-citationSenolytics 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-citationAged-senescent cells contribute to impaired heart regeneration
Lewis‐McDougall, F. C., Ruchaya, P. J., Domenjo‐Vila, E., Shin Teoh, T., Prata, L., Cottle, B. J., Clark, J. E., Punjabi, P. P., Awad, W., Torella, D., et al. (2019) · Aging Cell · doi:10.1111/acel.12931 · Cited by 317 · see citing works
Self-citationMitochondria, Oxidative Stress and Innate Immunity
Chen, Y., Zhou, Z., & Min, W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01487 · Cited by 315 · see citing works
“Indeed, our recent unpublished data have also revealed that Trx2-deletion induced mitochondrial dysfunction also lead to endothelial cell senescence and SASP in vivo and in vitro, which might further recruit innate immune cells to augment inflammatory responses.”
InfluentialThe Role of the Microbiota in Inflammation, Carcinogenesis, and Cancer Therapy
Dzutsev, A., Goldszmid, R. S., Viaud, S., Zitvogel, L., & Trinchieri, G. (2015) · European Journal of Immunology · doi:10.1002/eji.201444972 · Cited by 300 · see citing works
Senescence of T Lymphocytes: Implications for Enhancing Human Immunity
Akbar, A. N., Henson, S. M., & Lanna, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.09.002 · Cited by 285 · see citing works
Cellular 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 · see citing works
Nambiar, A., Kellogg, D., Justice, J., Goros, M., Gelfond, J., Pascual, R., Hashmi, S., Masternak, M., Prata, L., LeBrasseur, N., et al. (2023) · eBioMedicine · doi:10.1016/j.ebiom.2023.104481 · Cited by 298 · see citing works
Self-citationDNA damage response and metabolic disease
Shimizu, I., Yoshida, Y., Suda, M., & Minamino, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.008 · Cited by 286 · see citing works
Ke, Y., Li, D., Zhao, M., Liu, C., Liu, J., Zeng, A., Shi, X., Cheng, S., Pan, B., Zheng, L., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.01.007 · Cited by 285 · see citing works
Discovery of piperlongumine as a potential novel lead for the development of senolytic agents
Wang, Y., Chang, J., Liu, X., Zhang, X., Zhang, S., Zhang, X., Zhou, D., & Zheng, G. (2016) · Aging · doi:10.18632/aging.101100 · Cited by 274 · see citing works
Cellular senescence and the senescent secretory phenotype in age-related chronic diseases
Zhu, Y., Armstrong, J. L., Tchkonia, T., & Kirkland, J. L. (2014) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0000000000000065 · Cited by 273 · see citing works
Self-citationPhysiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty
Stout, M. B., Justice, J. N., Nicklas, B. J., & Kirkland, J. L. (2017) · Physiology · doi:10.1152/physiol.00012.2016 · Cited by 272 · see citing works
Self-citationDNA damage-induced type I interferon promotes senescence and inhibits stem cell function
Yu, Q., Katlinskaya, Y. V., Carbone, C. J., Zhao, B., Katlinski, K. V., Zheng, H., Guha, M., Li, N., Chen, Q., Yang, T., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.069 · Cited by 260 · see citing works
Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue
Schafer, M. J., White, T. A., Evans, G., Tonne, J. M., Verzosa, G. C., Stout, M. B., Mazula, D. L., Palmer, A. K., Baker, D. J., Jensen, M. D., et al. (2016) · Diabetes · doi:10.2337/db15-0291 · Cited by 267 · see citing works
Self-citationGrootaert, M. O., da Costa Martins, P. A., Bitsch, N., Pintelon, I., De Meyer, G. R., Martinet, W., & Schrijvers, D. M. (2015) · Autophagy · doi:10.1080/15548627.2015.1096485 · Cited by 267 · see citing works
Farr, J. N., & Khosla, S. (2019) · Bone · doi:10.1016/j.bone.2019.01.015 · Cited by 263 · see citing works
Macrophages in age-related chronic inflammatory diseases
Oishi, Y., & Manabe, I. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.18 · Cited by 262 · see citing works
Immune aging, dysmetabolism, and inflammation in neurological diseases
Deleidi, M., Jäggle, M., & Rubino, G. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00172 · Cited by 260 · see citing works
Telomere-driven diseases and telomere-targeting therapies
Martínez, P., & Blasco, M. A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610111 · Cited by 257 · see citing works
“JCB • Volume 216 • NumBer 4 • 2017876 late during life and secrete factors that influence age-associated diseases (Tchkonia et al., 2013).”
BackgroundGeorgilis, A., Klotz, S., Hanley, C. J., Herranz, N., Weirich, B., Morancho, B., Leote, A. C., D'Artista, L., Gallage, S., Seehawer, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.007 · Cited by 237 · see citing works
“Although genes belonging to either group are of biological interest, strategies to repress the SASP while maintaining the senescence growth arrest are appealing to target inflammation-driven tumorigenesis (Coppe et al., 2010; Tchkonia et al., 2013).”
BackgroundSenescent tumor cells lead the collective invasion in thyroid cancer
Kim, Y. H., Choi, Y. W., Lee, J., Soh, E. Y., Kim, J.-H., & Park, T. J. (2017) · Nature Communications · doi:10.1038/ncomms15208 · Cited by 253 · see citing works
Aging Hallmarks: The Benefits of Physical Exercise
Rebelo-Marques, A., De Sousa Lages, A., Andrade, R., Ribeiro, C. F., Mota-Pinto, A., Carrilho, F., & Espregueira-Mendes, J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00258 · Cited by 246 · see citing works
Ong, S.-M., Hadadi, E., Dang, T.-M., Yeap, W.-H., Tan, C. T.-Y., Ng, T.-P., Larbi, A., & Wong, S.-C. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0327-1 · Cited by 233 · see citing works
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · see citing works
Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice
Wong, C. K., Smith, C. A., Sakamoto, K., Kaminski, N., Koff, J. L., & Goldstein, D. R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700397 · Cited by 246 · see citing works
Molecular mechanisms of renal aging
Schmitt, R., & Melk, A. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.036 · Cited by 235 · see citing works
Tabibian, J. H., O'Hara, S. P., Trussoni, C. E., Tietz, P. S., Splinter, P. L., Mounajjed, T., Hagey, L. R., & LaRusso, N. F. (2016) · Hepatology · doi:10.1002/hep.27927 · Cited by 223 · see citing works
“Senescent cell clearance has only recently been explored, but may ultimately hold therapeutic promise in PSC (even in more advanced stages of disease) and other disorders.(44) In summary, by generating the first GF variant of the mdr2 murine model of PSC, we have demonstrated that the absence of the commensal microbio…”
BackgroundBiology 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-citationKiss, T., Nyúl-Tóth, Á., Balasubramanian, P., Tarantini, S., Ahire, C., DelFavero, J., Yabluchanskiy, A., Csipo, T., Farkas, E., Wiley, G., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00177-1 · Cited by 203 · see citing works
Iske, 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-citationThe chromatin accessibility signature of human immune aging stems from CD8+ T cells
Ucar, D., Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Uyar, A., Wu, T.-C., George, J., Stitzel, M. L., Palucka, A. K., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170416 · Cited by 200 · see citing works
Vascular senescence in cardiovascular and metabolic diseases
Katsuumi, G., Shimizu, I., Yoshida, Y., & Minamino, T. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00018 · Cited by 196 · see citing works
Therapeutic interventions for aging: the case of cellular senescence
Soto-Gamez, A., & Demaria, M. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.01.004 · Cited by 192 · see citing works
Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
Song, S., Lam, E. W.-F., Tchkonia, T., Kirkland, J. L., & Sun, Y. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.008 · Cited by 195 · see citing works
“Senescent cells passively accumulate in organs during aging, contributing to tissue dysfunction and pathological conditions [79].”
BackgroundSelf-citationFrailty in childhood cancer survivors
Ness, K. K., Armstrong, G. T., Kundu, M., Wilson, C. L., Tchkonia, T., & Kirkland, J. L. (2015) · Cancer · doi:10.1002/cncr.29211 · Cited by 188 · see citing works
Self-citationReducing Senescent Cell Burden in Aging and Disease
Pignolo, R. J., Passos, J. F., Khosla, S., Tchkonia, T., & Kirkland, J. L. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.005 · Cited by 177 · see citing works
Self-citationStrategies to Prevent Sarcopenia in the Aging Process: Role of Protein Intake and Exercise
Rogeri, P. S., Zanella, R., Martins, G. L., Garcia, M. D. A., Leite, G., Lugaresi, R., Gasparini, S. O., Sperandio, G. A., Ferreira, L. H. B., Souza-Junior, T. P., et al. (2021) · Nutrients · doi:10.3390/nu14010052 · Cited by 181 · see citing works
Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis
Stojanović, S. D., Fiedler, J., Bauersachs, J., Thum, T., & Sedding, D. G. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz919 · Cited by 188 · see citing works
- Authors
- Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Kirkland, James L.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-03-01
- Volume
- 123
- Issue
- 3
- Pages
- 966-972
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3582125
- OpenAlex
- W2108887402
- Cited by
- 1,774
- References
- 112
- Citations by year
- 2026: 129 · 2025: 138 · 2024: 163 · 2023: 150 · 2022: 142 · 2021: 180 · 2020: 162 · 2019: 145 · 2018: 138 · 2017: 122 · 2016: 105 · 2015: 92 · 2014: 72 · 2013: 33 · 2012: 1
- FWCI
- 11.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Ellison Medical Foundation
- Noaber Foundation
- National Institutes of Health (AG041122)
- National Institute on Aging (AG041122, P01AG041122)
- 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, senescence-associated secretory phenotype, aging, chronic inflammation, age-related diseases, frailty, senolytics, senolytic therapy
- MeSH terms
- Aging, Animals, Clinical Trials as Topic, DNA Damage, DNA Repair, Humans, Phenotype, Signal Transduction, Cellular Senescence, Inflammation Mediators, Molecular Targeted Therapy
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
