Aging has long since been ascribed to the gradual accumulation of DNA mutations in the genome of somatic cells. However, it is only recently that the necessary sophisticated technology has been developed to begin testing this theory and its consequences. Vijg critically reviews the concept of genomic instability as a possible universal cause of aging in the context of a new, holistic understanding of genome functioning in complex organisms resulting from recent advances in functional genomics and systems biology. It provides an up-to-date synthesis of current research, as well as a look ahead...