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.
Bibliographical noteFunding Information:
L.J.N. is supported by NIH/NIAP01 AG043376 and a sponsored research agreement from Aldabra Biosciences. J.L.K is supported by NIHAG13925, AG044396, and DK50456, the Connor Group, the Noaber, Ellison, and Glenn Foundations, and the American Federation for Aging Research. W.L. is supported by NIHR24 AG047115.
© 2016 Elsevier B.V.
- Aging endpoints
- Biological age
- Molecular pathology
- Surrogate markers of aging
- Translational biomarkers of aging