title: Molecular pathology endpoints useful for aging studies.
abstract: The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints.
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, United States. Electronic address: lniedern@scripps.edu.
authors.forename: L J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: J L
authors.initials: JL
authors.lastname: Kirkland
authors.affiliation: Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: W
authors.initials: W
authors.lastname: Ladiges
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology / Q000523:psychology; D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D008017:Life Expectancy; D008136:Longevity / Q000502:physiology*; D057089:Pathology, Molecular / Q000379:methods
chemical_list: D015415:Biomarkers
keywords: Aging endpoints; Biological age; Geropathology; Molecular pathology; Surrogate markers of aging; Translational biomarkers of aging