Aging rate indicators and the search for anti-aging drugs.

Evidence that drugs, diets, and single-gene mutations can slow aging and extend the healthy lifespan of mammals has begun to convert biogerontology from an observational science into one based on interventions that could provide people with additional years of healthy, productive life. However, the research and development of anti-aging drugs is hampered by the lack of instantaneous and continuous measures of the rate of aging itself. This article presents recent work on anti-aging drugs that are effective in mice, provides evidence for candidate "aging rate indicators" (ARIs), and outlines a roadmap for translating these into clinical research to slow aging in humans. Thus far, 14 agents or combinations have significantly increased the lifespan of mice in studies conducted under the Interventions Testing Program (ITP) of the National Institute on Aging, often when initiated in late adulthood. Recent evidence suggests that many, perhaps all, interventions that slow aging in mice induce common, shared changes in physiological status and molecular pathways. We have proposed 12 such mechanisms as candidate ARIs, i.e., measurable outcomes that reflect a slow-aging state and that could discriminate between normal mice (and perhaps humans) and those exposed to effective anti-aging interventions-thereby accelerating research. Research priorities now include testing the robustness of these ARIs, extending them to include plasma constituents, elucidating the mechanisms through which diverse interventions alter them, uncovering the links between the ARIs and late-life diseases, and extending research to dogs, non-human primates, and humans. The growing recognition of the legitimacy and promise of evidence-based interventions resulting from aging biology should elevate this field to a level of urgency and respect comparable to that of current research on individual age-related conditions.