Longer Lived Mammals Exhibit a Downregulated Methionine Metabolism
Long term restriction of dietary methionine intake is known to extend life in short-lived mammals. Methionine sensing is one of the triggers for the calorie restriction response, improving cell maintenance and adjusting metabolism into a state more resilient to the ongoing generation of molecular damage that contributes to degenerative aging. Researchers here note that methionine levels are lower in the heart tissue of longer-lived mammals, suggesting that altered methionine metabolism, maintaining lower levels of methionine in and around cells, is one of the adaptations that allows long-lived mammals to be long-lived. This may also go some way towards explaining why calorie restriction and related strategies such as methionine restriction have a lesser effect on life span in longer-lived species. Calorie restriction can increase mouse life span by as much as 40%, but cannot add more than a few years to human life span.
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. Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity. 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.