Stress resistance by caloric restriction for longevity.

Hardly an aspect of aging is more important than an organism's ability to withstand stress or to resist both internally and externally imposed insults. We know that as organisms loose their ability to resist these insults, aged organisms suffer more than the young. Therefore, a prime strategy for an organism's survival has been the evolutionarily adapted defense systems that guard against insult. For better survivability, an organism's defense system must be maximized to its full effect through well-coordinated networks of diverse biologically responsive elements. Although terms like stress, resistance, and adaptability have long been used in biology, they remain mechanistically and quantitatively poorly defined. In a gerontological context, stress resistance or susceptibility are often discussed in association with an organism's vulnerability to disease and age-related damage. However, to date, there is no clear molecular delineation of cellular and molecular mechanisms for such complex biological phenomena. The life-prolonging action of caloric restriction (CR) seems to offer an excellent opportunity for investigating the interrelationship between stress and the aging process. As an omnipotent intervention, CR provides a unique opportunity to probe the organism's ability to withstand age-related stress as a survival strategy. In this context, the antiaging action of CR can be viewed as "nutritional stress," because the organism's reduced caloric intake seems to be a stimulatory metabolic response for survivability. Recent gerontologic research has provided sufficient experimental data supporting this antiaging property of CR, of which several pertinent, key examples are discussed below.