Methionine restriction beyond life-span extension

Dietarymethionine restriction (MR) extends life span across species via various intracellular regulatory mechanisms. In rodents, MRinduces resistance against adiposity, improves hepatic glucose metabolism, preserves cardiac function, and reduces body size, all of which can affect the onset of age-related diseases. Recent studies have shown that MR-affected biomarkers, suchas fibroblast growth factor 21, adiponectin, leptin, cystathionine beta synthase, andinsulin-like growth factor 1, can potentially alter physiology. The beneficial effects ofMRcould be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed thatMR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that eitherMRor the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such asmethylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.