Effect of methionine restriction (MR) on DNA methylation was investigated. MR did not alter hepatic global DNA methylation (GM) in young mice (8 weeks). In adults (12 months), MR restored age-related decrease in hepatic GM to the levels observed in young mice. Changes in GM were negatively correlated with S-adenosylhomocysteine levels. Findings suggest that altered GM might be contributing to MR-induced lifespan extension.