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Caloric Restriction Mimetics

Metabolic Interventions

^a Department of Medicine, University of Wisconsin, Madison
^b Merck Research Laboratories, West Point, Pennsylvania
^c Centaur Pharmaceuticals, Inc., Sunnyvale, California
^d Department of Medicine, University of Texas Health Science Center, San Antonio
^e National Center for Toxicological Research, Jefferson, Arkansas
^f Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City
^g The Geriatrics Center, University of Michigan, Ann Arbor
^h Wisconsin Regional Primate Research Center, University of Wisconsin, Madison
ⁱ Department of Physiology, University of Texas Health Science Center, San Antonio
^j Molecular Physiology and Genetics Section, Gerontology Research Center, Baltimore, Maryland
^k Department of Biochemistry, University of California, Riverside

Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.

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