Rapamycin Joins the Aging Fray: Maybe Ponce de Leon Visited Rapa Nui, not Florida

Extract

FINDING methods for extending healthy life—life span—is a major goal of gerontologists. For a long time, the only method we knew of was caloric restriction. Although in many strains of mice and rats caloric restriction extends both life span and healthspan (in most but not all parameters measured), it is quite obvious that caloric restriction will not be widely applicable to humans unless the molecular mechanisms involved are identified and mimetics developed. Then, in the 1990s, spurred in part by the development of the Longevity Assurance Gene initiative of the National Institute on Aging (NIA), there was a significant interest in genetic manipulations that extend life span. Hundreds of such manipulations have been described in lower organisms, and they comprise a core of our current understanding of the aging process. However, applicability to humans again hinges on our ability to devise pharmacological modulators of the pathways identified. More recently, two such pathways, sirtuins and the mammalian target of rapamycin (mTOR), have led to the development of small molecule modulators that hold the promise of extending the life span, healthspan, or both. Namely, these are the sirtuin activator resveratrol and the mTOR inhibitor rapamycin.