title: Strategies and Challenges in Clinical Trials Targeting Human Aging.
abstract: Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study.
authors.affiliation: Division of Geriatrics, University of California San Francisco.
authors.forename: John C
authors.initials: JC
authors.lastname: Newman
authors.affiliation: Department of Medicine, Division of Endocrinology and.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Milman
authors.affiliation: Department of Hematology and Transplant Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Shahrukh K
authors.initials: SK
authors.lastname: Hashmi
authors.affiliation: Department of Biology, University of Alabama at Birmingham.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Austad
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.affiliation: Geriatrics Center and Institute of Gerontology, University of Michigan, Ann Arbor.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Halter
authors.affiliation: Department of Medicine, Division of Endocrinology and nir.barzilai@einstein.yu.edu.|Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D035843:Biomedical Research; D002986:Clinical Trials as Topic; D003226:Congresses as Topic; D004195:Disease Models, Animal; D004341:Drug Evaluation; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D012107:Research Design; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin; D020909:Acarbose; D020123:Sirolimus
keywords: Acarbose; Aging; Clinical trials; Metformin; Rapamycin