Human longevity is influenced by both inherited and environmental factors. Alterations in gene function that are related to inherited genetic mutations and polymorphisms can explain some features of aging and age-related diseases. However, in addition to inherited genetic factors, aging is influenced by the gradual accumulation of molecular alterations after birth. Epigenetic changes can influence gene function during aging without inherited and acquired DNA sequence alterations. In particular, promoter DNA methylation changes and associated gene silencing are epigenetic changes that are prominent in some cells and age-related diseases. Here, we review genetic approaches to understand aging, and discuss the potential role of epigenetic mechanisms in human aging and age-related diseases.