Role of Oxidative Stress in Aging

Abstract

The question of why we age has given rise to many different theories over the last decades. One of the most popular and long-lasting hypothesis is the free radical theory of aging. It postulates that endogenously generated reactive oxygen species (ROS) accumulate over time, causing damage to cellular macromolecules and eventually leading to physiological decline, disease, aging, and death. Over the years, a multitude of correlative evidence has been collected in favor of this aging theory, including the discovery that aging and many age-related diseases are accompanied by substantial cellular oxidative damage. However, genetic manipulation of components of cellular antioxidant defense systems in model organisms, like Caenorhabditis elegans, Drosophila melanogaster or mice have generated conflicting results and suggested a more complex interplay between endogenous oxidants, antioxidants, and lifespan. The fact that ROS play important roles as second messengers in signaling processes, in hormesis, and during the oxidative burst in innate immune cells, likely contributes to the complexity of this issue. In this chapter, we present an overview of the most crucial experiments conducted to address the free radical theory of aging. Our conclusion is that ROS are major players involved in lifespan and aging but likely not (only) in their role as cytotoxic agents but as regulators of essential physiological processes in the cell.