Age-related base excision repair activity in mouse brain and liver nuclear extracts

To assess DNA repair activity relative to age, in vitro base excision repair assays were performed using brain and liver nuclear extracts prepared from mice of various ages. An 85 % decline in repair activity was observed in brain nuclear extracts and a 50 % decrease in liver nuclear extracts prepared from old mice compared with 6-day-old mice. Brain nuclear extracts prepared from old mice showed a decreased abundance of DNA polymerase-b, but the addition of purified protein did not restore base excision repair activity. Abundances of other tested base excision repair proteins did not change relative to age. The conclusion is that, during aging, a decline in DNA repair could contribute to increased levels of DNA damage and mutagenesis. WHILE it is clear that organisms age and develop age-related pathologies such as cancer, conclusive identification of the mechanisms involved in aging remain elusive.More than 40 years ago, Failla (1) and Szilard (2) pro-posed the Somatic Mutation Theory of Aging. The theory proposes that a gradual accumulation of mutations occurs with increasing age, thereby leading to cellular dysfunction and a breakdown of homeostasis. A role for genetic in