Cellular Senescence: A Translational Perspective

James L Kirkland, Tamara Tchkonia

Research output: Contribution to journalArticle

140 Citations (Scopus)

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.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Mar 13 2017

Fingerprint

Cell Aging
Aging of materials
Geriatrics
Tissue
Phenotype
Stem cells
Apoptosis
Chronic Disease
Pharmaceutical Preparations
Cell Survival
Stem Cells
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cellular Senescence : A Translational Perspective. / Kirkland, James L; Tchkonia, Tamara.

In: EBioMedicine, 13.03.2017.

Research output: Contribution to journalArticle

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