The effects of aging and oxidative stress on learning behavior in C. elegans.

Oxidative stress is associated with age-related declines of biological functions. However, the nervous system is preserved during aging in Caenorhabditis elegans and, thus, it is not well explored whether aging and oxidative stress affect nervous functions. Here we report that age-related decline can be observed in a type of associative-learning behavior, referred to as isothermal tracking. We also report the effects of mutants with altered sensitivity to oxidative stress on learning behavior and motor activity in young adults. The isp-1 and clk-1 mutants are members of the Clk class of mutants and have deficits in the function of the mitochondrial respiratory chain, leading to reduced levels of oxidative stress, increased longevity, delayed rhythmic behaviors and other phenotypes. Both the Clk mutations and pretreatment with a metabolic antioxidant, alpha-lipoic acid (LA), increased the ability to show isothermal tracking and modestly reduced motor activity. Mutants with increased oxidative stress showed severely impaired learning behavior and modestly reduced motor activity. Therefore, physiological levels of oxidative stress may be too high for learning behavior but, perhaps, not for motor activity. We discuss the relevance of oxidative stress to the aging and evolution of behaviors.