Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism

Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during ageing and extends lifespan in diverse species including rodents and rhesus monkeys. However the mechanisms by which DR interacts with the ageing process to improve health at old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR, because it is sensitive to the effects of nutrition and can affect gene expression memory over time. Here we have profiled genome-wide changes in DNA methylation, gene expression and lipidomics in response to DR and ageing in mouse liver. DR strongly retarded age-related changes in DNA methylation. With ageing, DNA methylation became confined to genic elements and was associated with reduced gene expression, particularly of genes involved in lipid metabolism.