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Reducing Senescent Cell Burden in Aging and Disease.

ABSTRACT: Cellular senescence is a primary aging process and tumor suppressive mechanism characterized by irreversible growth arrest, apoptosis resistance, production of a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and alterations in DNA and chromatin. In preclinical aging models, accumulation of senescent cells is associated with multiple chronic diseases and disorders, geriatric syndromes, multimorbidity, and accelerated aging phenotypes. In animals, genetic and pharmacologic reduction of senescent cell burden results in the prevention, delay, and/or alleviation of a variety of aging-related diseases and sequelae. Early clinical trials have thus far focused on safety and target engagement of senolytic agents that clear senescent cells. We hypothesize that these pharmacologic interventions may have transformative effects on geriatric medicine.

SUBMITTER: Pignolo RJ

PROVIDER: S-EPMC7857028 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Reducing Senescent Cell Burden in Aging and Disease.

Pignolo Robert J RJ Passos João F JF Khosla Sundeep S Tchkonia Tamara T Kirkland James L JL

Trends in molecular medicine 20200417 7

Cellular senescence is a primary aging process and tumor suppressive mechanism characterized by irreversible growth arrest, apoptosis resistance, production of a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and alterations in DNA and chromatin. In preclinical aging models, accumulation of senescent cells is associated with multiple chronic diseases and disorders, geriatric syndromes, multimorbidity, and accelerated aging phenotypes. In animals, genetic and pharmac ...[more]

PMID: 32589933

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