Age-related decline in cellular response to oxidative stress: links to growth factor signaling pathways with common...

Accumulation of oxidative damage is believed to be a major contributor to the decline in physiologic function that characterizes mammalian aging, and recent studies suggest that how well you respond to acute oxidative stress is an important factor in determining longevity. Oxidant injury elicits a wide spectrum of responses ranging from proliferation to cell death. The particular outcome observed largely reflects the severity of the stress encountered and the relative degree of activation of various signal transduction pathways aimed at enhancing survival or inducing cell death. Herein we examine the relationship between pathways important in supporting cell survival in response to oxidant injury and those involved in regulating proliferation. We review evidence indicating that [Curr. Opin. Cell Biol. 10 (1998) 248] common pathways are indeed involved in regulating these responses, and [Physiol. Rev. 82 (2002) 47] alterations in shared signaling events likely account for the age-related decline in the ability of cells to respond to both proliferative signals and oxidant stimuli.