Aging and Genome Maintenance: Lessons from the Mouse?

Recent progress in the science of aging is driven largely by the use of model systems, ranging from yeast and nematodes to mice. These models have revealed conserva-tion in genetic pathways that balance energy production and its damaging by-products with pathways that preserve somatic maintenance. Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for under-standing the molecular basis of aging in humans. The accumulation of somatic damage is now considered a main cause of the aging process in species varying from nematodes and insects to mice and humans. Among the various sources of somatic damage, reactive oxygen species (ROS), the natural by-products of oxidative en-ergy metabolism, are often considered as the ultimate cause of aging (1). However, free rad