Methionine restriction and mimetics to ameliorate human aging and disease

Methionine restriction (MetR) attenuates the severity of numerous age-related diseases and extends lifespan across multiple species. Implementing MetR in humans remains challenging due to the low palatability of MetR diets, unfavorable side effects associated with continuous dietary MetR, and interindividual variation in factors that can diminish its efficacy, including microbiota activity, compensatory effects from cysteine, and methionine transfer from neighboring cells. Several novel approaches that target methionine metabolism have been developed - including small molecules, synthetic biotics, and xenotopic tools - with some already translated into early-stage clinical trials. In this review, we discuss a variety of approaches that either produce or mimic MetR, as well as their potential applications for human healthspan improvement.