For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
97
views
140
references
 Top references
cited by
476
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      864
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Senescent cells: an emerging target for diseases of ageing

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.

          Related collections

          Most cited references140

          • Record: found
          • Abstract: found
          • Article: found

          Aging, Cellular Senescence, and Cancer

          Judith Campisi (2013)
          For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action.
          Article 0 comments Cited 1129 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cellular senescence in aging and age-related disease: from mechanisms to therapy.

            Bennett Childs, Matej Durik, Darren J. Baker … (2015)
            Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.
            Article 0 comments Cited 880 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

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

              Yi-Yi Zhu, Tamara Tchkonia, Tamar Pirtskhalava … (2015)
              The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1 −/Δ mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1 −/Δ mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.
              Article 0 comments Cited 873 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101124171
                Journal ID (pubmed-jr-id): 29776
                Journal ID (nlm-ta): Nat Rev Drug Discov
                Journal ID (iso-abbrev): Nat Rev Drug Discov
                Title: Nature reviews. Drug discovery
                ISSN (Print): 1474-1776
                ISSN (Electronic): 1474-1784
                Publication date Nihms-submitted: 19 April 2018
                Publication date (Electronic): 21 July 2017
                Publication date (Print): October 2017
                Publication date PMC-release: 09 May 2018
                Volume: 16
                Issue: 10
                Pages: 718-735
                Affiliations
                [1 ]Departments of Biochemistry and Molecular Biology, Mayo Clinic
                [2 ]Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905, USA
                [3 ]Unity Biotechnology, 3280 Bayshore Boulevard Suite 100, Brisbane, California 94005, USA
                Author notes
                Correspondence to J.M.v.D. vanDeursen.Jan@ 123456mayo.edu
                Article
                Accession ID: PMC5942225 Pmcid ID: PMC5942225 Pmc-uid ID: 5942225 Manuscript ID: nihpa960772
                DOI: 10.1038/nrd.2017.116
                PMC ID: 5942225
                PubMed ID: 28729727
                SO-VID: 0e857c9d-d9df-44eb-b999-fe1a69a4b328
                History
                Categories
                Subject: Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content864

                See all similar

                Cited by468

                See all cited by

                Most referenced authors4,205

                See all reference authors