title: Clinical strategies and animal models for developing senolytic agents.
abstract: Aging is associated with increasing predisposition to multiple chronic diseases. One fundamental aging process that is often operative at sites of the pathology underlying chronic age-related diseases is cellular senescence. Small molecule senolytic agents are being developed. For successful drug development: 1) appropriate animal models of human age-related diseases need to be devised. 2) Models have to be made in which it can be proven that beneficial phenotypic effects are actually caused through clearing senescent cells by putative senolytic agents, as opposed to "off-target" effects of these agents on non-senescent cells. 3) Models are needed to test efficacy of drugs and to uncover potential side effects of senolytic agents. Development of the optimal animal models and clinical trial paradigms for senolytic agents warrants an intensive effort, since senolytic agents, if successful in delaying, preventing, alleviating, or reversing age-related diseases as a group would be transformative.
authors.affiliation: Mayo Clinic Robert and Arlene Kogod Center on Aging, 200 First Street, S.W., Rochester, MN 55905, United States. Electronic address: Kirkland.james@mayo.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.affiliation: Mayo Clinic Robert and Arlene Kogod Center on Aging, 200 First Street, S.W., Rochester, MN 55905, United States.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tchkonia
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D016922:Cellular Senescence / Q000187:drug effects; D002908:Chronic Disease; D006233:Persons with Disabilities; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D023421:Models, Animal
keywords: Cellular senescence; Healthspan; Senescence-associated secretory phenotype; Senolytic