Caloric restriction regulates epigenetic pathways. Caloric restriction (CR) influences epigenetic processes via two primary mechanisms: DNA methylation and histone modification. DNA methylation regulation during CR involves DNMT activation, resulting in silencing the expression of target genes such as p16
INK4a and Ras due to hypermethylation of these genes. CR-induced histone remodeling primarily includes histone acetylation and methylation. Deacetylation effects due to activation of SIRT1 and HDAC1 by CR lead to expression changes of key genes such as p53, Foxo, Ku70, PGC-1α and p16
INK4a. Histone methylation also plays a role in the regulation of key gene expression, including hTERT and p16
INK4a. As a result, epigenetic regulation actively reverses aberrant gene expression during CR, which contributes to CR-associated aging delay and lifespan extension.