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EBioMedicine. 2017 Jul;21:21-28. doi: 10.1016/j.ebiom.2017.04.013. Epub 2017 Apr 12.

Cellular Senescence: A Translational Perspective.

Author information

1
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States. Electronic address: kirkland.james@mayo.edu.
2
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States.

Abstract

Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

KEYWORDS:

A1155463; A1331852; Dasatinib; Fisetin; Navitoclax; Quercetin; SASP inhibitors; Senescent Cell Anti-apoptotic Pathways (SCAPs); Senolytics

PMID:
28416161
PMCID:
PMC5514381
DOI:
10.1016/j.ebiom.2017.04.013
[Indexed for MEDLINE]
Free PMC Article

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