Current issues concerning the role of oxidative stress in aging: a perspective.

The main tenet of the oxidative stress hypothesis of aging is that accrual of molecular oxidative damage is the principal causal factor in the senescence-related loss of ability to maintain homeostasis. This hypothesis has garnered a considerable amount of supportive correlational evidence, which is now being extended experimentally in transgenic Drosophila over-expressing antioxidative defense enzymes. Some of these studies have reported extensions of life span, while others have not. Interpretation of life spans in poikilotherms is complicated by a number of factors, including the interrelationship between metabolic rate and longevity. The life spans of poikilotherms can be extended multi-fold by reducing the metabolic rate but without affecting the metabolic potential, i.e., the total amount of energy expended during life. A hypometabolic state in poikilotherms also enhances stress resistance and activities of antioxidative enzymes. It is emphasized that extension of life span without simultaneously increasing metabolic potential is of questionable biological significance.