The goal of this chapter is to critically examine the possible contributions of oxidative damage, exercise, and caloric restriction (CR) to health in later life by defi ning these quantities, discussing experimental studies that suggest their importance for particular measures of health and then evaluating their role in the determination of health span. The timing, duration, and combination of these factors contribute to environment, a major determinant of longevity. Current information indicates that genetic inheritance contributes no more than 35% of an individual' s longevity, implying personal choices in lifestyle greatly impact health and health span. Physical activity is known to promote longevity and health, whereas physical inactivity promotes obesity and augments the risk of endocrine, nutritional, and age-associated diseases. The balance of biomarkers of oxidative stress (such as plasma protein carbonyls, nitrotyrosine, and malondialdehyde) and those of antioxidant status (such as oxygen radical absorbance capacity) may provide some indication of health. Individual differences in the physiological function of the infl ammatory and heat-shock responses may also impact aging and health span. CR is one of the most robust and reliable means of improving health and performance in old age. This regimen of decreasing food intake has been demonstrated to extend longevity and increase vitality in
CELLS TO HOMEOSTATIC SYSTEMS
ANNUAL REVIEW OF GERONTOLOGY AND GERIATRICSa wide range of organisms under laboratory conditions. Preliminary results in monkeys and men and women are encouraging for promoting health span, if not life span. However, recent data indicate that genetic background is important in these effects, suggesting caution should be exercised in applying CR in freeliving men and women. Compounds capable of inducing such effects without the need to reduce feeding recently have been identifi ed and are in the process of widespread testing. Possibilities for extending the health span using exercise and CR-like effects thus appear promising, but undesirable side effects must also be recognized and accommodated.