TY - JOUR
T1 - Reducing Senescent Cell Burden in Aging and Disease
AU - Pignolo, Robert J.
AU - Passos, João F.
AU - Khosla, Sundeep
AU - Tchkonia, Tamara
AU - Kirkland, James L.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083319416&partnerID=8YFLogxK
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U2 - 10.1016/j.molmed.2020.03.005
DO - 10.1016/j.molmed.2020.03.005
M3 - Review article
C2 - 32589933
AN - SCOPUS:85083319416
SN - 1471-4914
VL - 26
SP - 630
EP - 638
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 7
ER -