Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan?

Abstract

With few exceptions, nutritional and dietary interventions generally impact upon both old-age quality of life and longevity. The life prolonging effects, commonly observed with dietary restriction reportedly are linked to alterations in protein intake and specifically limiting the dietary intake of certain essential amino acids. There is however a paucity of data methodically evaluating the various essential amino acids on health- and lifespan and the mechanisms involved. Rodent diets containing either lower methionine content, or tryptophan, than that found in commercially available chow, appear to elicit beneficial effects. It is unclear whether all of these favorable effects associated with restricted intake of methionine and tryptophan are due to their specific unique properties or if restriction of other essential amino acids, or proteins in general, may produce similar results. Considerably more work remains to be done to elucidate the mechanisms by which limiting these vital molecules may delay the onset of age-associated diseases and improve quality of life at older ages.

l‐Methionine activates Nrf2‐ARE pathway to induce endogenous antioxidant activity for depressing ROS‐derived oxidative stress in growing rats

“…Some studies examining aging‐related outcomes and longevity in rodents consuming methionine‐deficient diets have shown beneficial effects of methionine restriction on metabolic health and lifespan . It appeared that methionine restriction may itself directly activate Nrf2, and that a methionine‐restricted diet enhances the activity of antioxidant enzymes, and reduces ROS production and oxidative stress damage . In this study, we did not investigate whether the oral administration of l ‐ methionine could influence the lifespan extension.…”

Short‐term methionine deprivation improves metabolic health via sexually dimorphic, mTORCI‐independent mechanisms

“…Dietary MR produces many beneficial effects on metabolic health in both rodents and humans, preventing weight gain and fat accretion, and improving control of blood glucose (10, 18, 43, 44). However, humans have significant difficulties in remaining compliant with severe dietary alterations.…”

“…The mechanisms by which MR promotes metabolic health and longevity have been investigated at length but remain poorly understood (18). Many of the metabolic benefits of MR have been attributed to increased levels of the hormone fibroblast growth factor (Fgf)-21, which promotes hepatic insulin sensitivity and increases energy expenditure.…”

Factors that affect the translation of dietary restriction into a longer life

“…Nevertheless, studies performed in a number of animal species have shown that protein restriction increases both lifespan and healthy lifespan, implying that these effects involve evolutionarily conserved mechanisms that might also be operational in humans . The positive effects on lifespan achieved using diets with low protein or amino acid content can also be achieved by reductions in specific amino acids, with substantial restriction of methionine being most effective . Moreover, this reduction in methionine levels changes the cellular metabolism and has a supportive effect in cancer treatment .…”