Long Lived Mammals Exhibit Lower Plasma Methionine Levels
Mechanisms to sense levels of the essential amino acid methionine are one of the more important triggers for the beneficial calorie restriction response in mammals. Since the body doesn't manufacture methionine, it must come from the diet. Either a low calorie diet or a low methionine diet produce broadly similar effects of improved metabolism, health, and longevity, though different in the fine details. Short-lived species, however, have a much larger gain in life span than is the case in longer-lived species. Calorie restriction can make mice live 40% longer, but it certainly doesn't add more than a few years in humans.
Why this is the case, when short-term metabolic responses and benefits appear broadly similar in both short-lived and long-lived mammals, is an open question. In this context, the research here is quite interesting. If background levels of methionine are lower in long-lived species, perhaps the shared trigger mechanisms relating to methionine are less capable of producing sizable effects in long-term health - though again, a detailed understanding of exactly how this happens has yet to be established.
All living organisms use the same 20 amino acids for protein synthesis. Interestingly, the protein compositional content of the sulfur amino acids methionine and cysteine is species-specific and is associated with animal longevity. Thus, long-lived animal species show the lower methionine and cysteine protein content, surely as adaptive response to the low rate of endogenous damage and highly resistant macromolecular components also present in longevous species. Reinforcing these observations, the free tissue methionine content is also lower in diverse long-lived animal species; and the pro-longevity effects of nutritional (methionine restriction, MetR) and pharmacological (metformin) interventions are mediated by changes in methionine metabolism.
In addition to its role in several intracellular processes, methionine is the core of a complex metabolic network which can be divided in three parts: methionine cycle, the transsulfuration pathway, and polyamine biosynthesis. Significantly, manipulation of each of these branches affects longevity in diverse experimental animal models. Consequently, available findings point to the metabolism of methionine as a key target to study the molecular adaptive mechanisms underlying differences in animal longevity.
The present study follows a comparative approach to analyse the plasma methionine metabolic profile from 11 mammalian species with a longevity ranging from 3.5 to 120 years. Our findings demonstrate the existence of a species-specific plasma profile for methionine metabolism associated with longevity characterised by: i) reduced methionine, cystathionine and choline; ii) increased non-polar amino acids; iii) reduced succinate and malate; and iv) increased carnitine. Our results support the existence of plasma longevity features that might respond to an optimised energetic metabolism and intracellular structures found in long-lived species.