Oxidative stress in aging: stayin’ alive?

Abstract

There is still ongoing controversy about the oxidative stress theory of aging, particularly in mammals, after a significant number of studies have been conducted to test this theory. Results generated from the studies strongly indicate that accumulation of oxidative damage alone does not play a significant role as an underlying mechanism of aging, which calls into question that significant modifications to the theory are required to understand the relationship between oxidative stress and aging. To examine the exact role of oxidative stress in aging and age-related diseases, our laboratory has been conducting studies with unique animal models: 1) mice overexpressing or down-regulating thioredoxin (Trx) in the cytosol (Trx1) or in mitochondria (Trx2); and 2) rats overexpressing Cu/Zn superoxide dismutase (SOD). Results generated from these studies strongly indicate that: 1) changes in oxidative stress and redox state could play more important roles in age-related pathological changes, e.g., cancer and metabolic disorders; 2) redox regulation of signaling pathways could play more important roles in aging than accumulation of oxidative damages; 3) the potential benefit of changes in oxidative stress and redox state could be organ/tissue specific; 4) the roles of oxidative stress could vary in different stages of life (i.e., young versus old); and 5) synergetic effects of changes in oxidative stress in multiple cellular compartments may be required to have a significant impact on aging. Therefore, the studies with more careful approach would uncover the exact roles and pathophysiological consequences of oxidative stress during aging. Keywords: Oxidative stress, aging, age-related diseases, cancer, obesity, healthspan