A sustained state of
methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously
methionine-restricted rodents have less age-related pathology and are up to 45% longer-lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that
methionine-restricted individuals may receive similar benefits to rodents. However, long-term adherence to a
methionine-restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan-extending interventions (i.e., intermittent fasting and the cyclic
ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR. Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved
glucose homeostasis and protection against diet-induced
obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the
hormones IGF-1,
FGF-21,
leptin, and
adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.