Methionine Metabolism Is Down-Regulated in Heart of Long-Lived Mammals

SIMPLE SUMMARY: Long-lived species have evolved by reducing the rate of aging, which is an inherent consequence of oxidative metabolism. Hence, species that live longer benefit from more efficient intracellular metabolic pathways, including lipid, protein, and carbohydrate metabolism. The aim of this work is to determine whether the content of proteins’ building blocks, named amino acids, are related with mammalian longevity. This was accomplished by analyzing the amino acid content in the hearts of seven mammalian species with a longevity ranging from 3.8 to 57 years. Our findings demonstrate that the heart’s content of amino acids differs between species and is globally lower in long-lived species. Moreover, long-lived species have lower content of amino acids containing sulfur, such as methionine and its related metabolites. Our results support the existence of metabolic adaptations in terms of sulfur-containing amino acids. As has been described previously, our work supports the idea that the human population could benefit from reduced calorie intake, which would lead to reduced age-related diseases and healthier aging. ABSTRACT: Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolite and amino acid profiles using an LC-MS/MS platform in the hearts of seven mammalian species with a longevity ranging from 3.8 to 57 years. Our findings demonstrate the existence of species-specific heart phenotypes associated with high longevity characterized by: (i) low concentration of methionine and its related sulphur-containing metabolites; (ii) low amino acid pool; and (iii) low choline concentration. Our results support the existence of heart metabotypes characterized by a down-regulation in long-lived species, supporting the idea that in longevity, less is more.