Context‐dependent roles of cellular senescence in normal, aged, and disease states

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors

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The Hallmarks of Aging

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The serial cultivation of human diploid cell strains

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A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

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A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.

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Cellular Senescence: Defining a Path Forward

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Osteoarthritis: A disease of the joint as an organ

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ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

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Aging, Cellular Senescence, and Cancer

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Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

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Cellular senescence: from physiology to pathology

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The role of senescent cells in ageing

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Hallmarks of Cellular Senescence

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The Achilles' heel of senescent cells: from transcriptome to senolytic drugs

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Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

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Senolytics improve physical function and increase lifespan in old age

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Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence

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A complex secretory program orchestrated by the inflammasome controls paracrine senescence

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Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion

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Idiopathic pulmonary fibrosis

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An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA

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Senescence of activated stellate cells limits liver fibrosis

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Senescence of Activated Stellate Cells Limits Liver Fibrosis

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Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice

Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819 · see citing works

Multiple Sclerosis: An Immune or Neurodegenerative Disorder?

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Pathology of Neurodegenerative Diseases

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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

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 · see citing works

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment

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 · see citing works

Ink4a/Arf expression is a biomarker of aging

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Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454 · see citing works

Senescence-associated β-galactosidase is lysosomal β-galactosidase.

Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444 · see citing works

Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016

Xie, Y., Bowe, B. C., Mokdad, A. H., Xian, H., Yan, Y., Li, T., Maddukuri, G. S., Tsai, C.-Y., Floyd, T., & Al‐Aly, Z. (2018) · Kidney International · doi:10.1016/j.kint.2018.04.011 · Cited by 1,397 · see citing works

Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease

Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.069 · Cited by 1,383 · see citing works

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 · see citing works

A proteomic atlas of senescence-associated secretomes for aging biomarker development

Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., Holtz, A., Shah, S., Sharma, V., Ferrucci, L., et al. (2020) · PLOS Biology · doi:10.1371/journal.pbio.3000599 · Cited by 1,348 · see citing works

Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury

Yang, L., Besschetnova, T. Y., Brooks, C. R., Shah, J. V., & Bonventre, J. V. (2010) · Nature Medicine · doi:10.1038/nm.2144 · Cited by 1,333 · see citing works

Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline

Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018) · Nature · doi:10.1038/s41586-018-0543-y · Cited by 1,289 · see citing works

Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study

Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.12.052 · Cited by 1,261 · see citing works

NAD ⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice

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Senescence and aging: Causes, consequences, and therapeutic avenues

McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233 · see citing works

Mechanisms and functions of cellular senescence

Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works

Senescent intimal foam cells are deleterious at all stages of atherosclerosis

Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016) · Science · doi:10.1126/science.aaf6659 · Cited by 1,195 · see citing works

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

Forging a signature of in vivo senescence

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Senolytic CAR T cells reverse senescence-associated pathologies

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Endothelial Cell Senescence in Human Atherosclerosis: Role of Telomere in Endothelial Dysfunction

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The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

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Lamin B1 loss is a senescence-associated biomarker

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Geriatric muscle stem cells switch reversible quiescence into senescence

Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A. L., et al. (2014) · Nature · doi:10.1038/nature13013 · Cited by 1,010 · see citing works

The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing

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In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.

Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., Li, M., Lam, D., Kurita, M., Beyret, E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.052 · Cited by 988 · see citing works

Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model

Zhang, P., Kishimoto, Y., Grammatikakis, I., Gottimukkala, K., Cutler, R. G., Zhang, S., Abdelmohsen, K., Bohr, V. A., Misra Sen, J., Gorospe, M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0372-9 · Cited by 977 · see citing works

Unmasking Transcriptional Heterogeneity in Senescent Cells

Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972 · see citing works

An aged immune system drives senescence and ageing of solid organs

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JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age

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

Immunosenescence: emerging challenges for an ageing population

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Non-Cell-Autonomous Tumor Suppression by p53

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Identification of HSP90 inhibitors as a novel class of senolytics

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Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance

Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., Meldrum, E., Sanders, Y. Y., & Thannickal, V. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008182 · Cited by 686 · see citing works

Rejuvenation of the muscle stem cell population restores strength to injured aged muscles

Cosgrove, B. D., Gilbert, P. M., Porpiglia, E., Mourkioti, F., Lee, S. P., Corbel, S. Y., Llewellyn, M. E., Delp, S. L., & Blau, H. M. (2014) · Nature Medicine · doi:10.1038/nm.3464 · Cited by 677 · see citing works

The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.

Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., Sansom, O. J., Zender, L., & Keyes, W. M. (2017) · Genes & Development · doi:10.1101/gad.290635.116 · Cited by 650 · see citing works

Senescence impairs successful reprogramming to pluripotent stem cells

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Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors

Gandhi, L., Camidge, D. R., Ribeiro de Oliveira, M., Bonomi, P., Gandara, D., Khaira, D., Hann, C. L., McKeegan, E. M., Litvinovich, E., Hemken, P. M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.6208 · Cited by 603 · see citing works

Tau protein aggregation is associated with cellular senescence in the brain

Musi, N., Valentine, J. M., Sickora, K. R., Baeuerle, E., Thompson, C. S., Shen, Q., & Orr, M. E. (2018) · Aging Cell · doi:10.1111/acel.12840 · Cited by 595 · see citing works

Tissue damage and senescence provide critical signals for cellular reprogramming in vivo

Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R. M., Chondronasiou, D., Rovira, M., Fernandez-Marcos, P. J., Muñoz-Martin, M., Blanco-Aparicio, C., Pastor, J., et al. (2016) · Science · doi:10.1126/science.aaf4445 · Cited by 589 · see citing works

Impaired immune surveillance accelerates accumulation of senescent cells and aging

Ovadya, Y., Landsberger, T., Leins, H., Vadai, E., Gal, H., Biran, A., Yosef, R., Sagiv, A., Agrawal, A., Shapira, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07825-3 · Cited by 578 · see citing works

T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

Desdín-Micó, G., Soto-Heredero, G., Aranda, J. F., Oller, J., Carrasco, E., Gabandé-Rodríguez, E., Blanco, E. M., Alfranca, A., Cussó, L., Desco, M., et al. (2020) · Science · doi:10.1126/science.aax0860 · Cited by 572 · see citing works

Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state

Lapasset, L., Milhavet, O., Prieur, A., Besnard, E., Babled, A., Aït-Hamou, N., Leschik, J., Pellestor, F., Ramirez, J.-M., De Vos, J., et al. (2011) · Genes & Development · doi:10.1101/gad.173922.111 · Cited by 570 · see citing works

Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective

Zaccardi, F., Webb, D. R., Yates, T. E., & Davies, M. J. (2015) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133281 · Cited by 570 · 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

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 · see citing works

Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums

Ravichandran, K. S. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20101157 · Cited by 547 · see citing works

Length-independent telomere damage drives post-mitotic cardiomyocyte senescence

Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · see citing works

Cellular Senescence Is Induced by the Environmental Neurotoxin Paraquat and Contributes to Neuropathology Linked to Parkinson’s Disease

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 · see citing works

Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis

Yao, C., Guan, X., Carraro, G., Parimon, T., Liu, X., Huang, G., Mulay, A., Soukiasian, H. J., David, G., WEIGT, S. S., et al. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202004-1274oc · Cited by 527 · see citing works

NOTCH1 mediates a switch between two distinct secretomes during senescence

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Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice

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Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells

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Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells

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p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes

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Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

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Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency

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Whole‐body senescent cell clearance alleviates age‐related brain inflammation and cognitive impairment in mice

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Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis <i>ex vivo</i>

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Senescent cells and osteoarthritis: a painful connection

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Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

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Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice

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Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability

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NKG2D ligands mediate immunosurveillance of senescent cells

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Cellular senescence: at the nexus between ageing and diabetes

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The role of cellular senescence in cardiac disease: basic biology and clinical relevance

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Metformin limits osteoarthritis development and progression through activation of AMPK signalling

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Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity

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Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

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Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice

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Cellular senescence in development, regeneration and disease

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Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle

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p21 produces a bioactive secretome that places stressed cells under immunosurveillance

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Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice

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Cellular Senescence in Neurodegenerative Diseases

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Characterization of bone marrow-derived mesenchymal stem cells in aging

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Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity

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Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model

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TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence

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Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction

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Essential role for premature senescence of myofibroblasts in myocardial fibrosis

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Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis

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Aging and the Burden of Multimorbidity: Associations With Inflammatory and Anabolic Hormonal Biomarkers

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Granule exocytosis mediates immune surveillance of senescent cells

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Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair

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Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells

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A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells

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Review: a meta‐analysis of GWAS and age‐associated diseases

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Quercetin Enhances Ligand-induced Apoptosis in Senescent Idiopathic Pulmonary Fibrosis Fibroblasts and Reduces Lung Fibrosis <i>In Vivo</i>

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Senescent Cardiac Fibroblast Is Critical for Cardiac Fibrosis after Myocardial Infarction

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Cellular senescence in the glaucomatous outflow pathway

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A comparative analysis of the cell biology of senescence and aging

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Local intra-articular injection of rapamycin delays articular cartilage degeneration in a murine model of osteoarthritis

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Senescence cell–associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers

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p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle

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Senescence promotes in vivo reprogramming through p16<scp>^INK</scp>^4a and <scp>IL</scp>‐6

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Cellular Senescence Limits Regenerative Capacity and Allograft Survival

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Apoptosis signal-regulating kinase 1 mediates cellular senescence induced by high glucose in endothelial cells

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Systemic clearance of p16 INK4a ‐positive senescent cells mitigates age‐associated intervertebral disc degeneration

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Doxorubicin induces senescence and impairs function of human cardiac progenitor cells

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Nrf2-Mediated Fibroblast Reprogramming Drives Cellular Senescence by Targeting the Matrisome

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The diagnosis of primary biliary cirrhosis

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Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia

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Paracrine cellular senescence exacerbates biliary injury and impairs regeneration

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Expression of p16<scp>^INK</scp>^4a is a biomarker of chondrocyte aging but does not cause osteoarthritis

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Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy

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Increased Expression of Senescence-Associated Cell Cycle Inhibitor p16 in Deteriorating Renal Transplants and Diseased Native Kidney

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Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence

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IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity

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Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice

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Direct reprogramming 101

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