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 - Funding Information:
This work was supported by the Robert and Arlene Kogod Professorship (RJP); National Institutes of Health P01 AG062413 (S.K., J.L.K., T.T., R.J.P.), P01 AG004875 (S.K.), R01 AG048792 (S.K.), R37 AG 013925 (J.L.K.), and R33 061456 (J.L.K.), as well as the Connor Group (J.L.K.), Robert and Theresa Ryan Foundation (J.L.K.), the Noaber Foundation (J.L.K.), and the Ted Nash Foundatio n (J.F.P.).
Funding Information:
This work was supported by the Robert and Arlene Kogod Professorship (RJP); National Institutes of Health P01 AG062413 (S.K. J.L.K. T.T. R.J.P.), P01 AG004875 (S.K.), R01 AG048792 (S.K.), R37 AG 013925 (J.L.K.), and R33 061456 (J.L.K.), as well as the Connor Group (J.L.K.), Robert and Theresa Ryan Foundation (J.L.K.), the Noaber Foundation (J.L.K.), and the Ted Nash Foundation (J.F.P.). J.L.K. and T.T. have a financial interest related to this opinion piece. Patents on senolytic drugs are held by Mayo Clinic. Research findings cited in this opinion piece were previously reviewed by the Mayo Clinic Conflict of Interest Review Board and were conducted in compliance with Mayo Clinic Conflict of Interest policies. No conflicts of interest, financial or otherwise, are declared by the other authors.
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.
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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
VL - 26
SP - 630
EP - 638
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 7
ER -