DNA Damage and the Aging Epigenome

In mammals, genome instability and aging are intimately linked as illustrated by the growing list of patients with progeroid and animal models with inborn DNA repair defects. Until recently, DNA damage was thought to drive aging by compromising transcription or DNA replication, thereby leading to age-related cellular malfunction and somatic mutations triggering cancer. However, recent evidence suggests that DNA lesions also elicit widespread epigenetic alterations that threaten cell homeostasis as a function of age. In this review, we discuss the functional links of persistent DNA damage with the epigenome in the context of aging and age-related diseases.