Abstract
Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content. The present study follows a comparative approach to analyse plasma methionine metabolic profile using a LC-MS/MS platform 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.
Highlights
Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content
In order to determine whether plasma methionine and its related metabolites concentration differed among mammals, multivariate statistics were applied
The performance of a Random forest (RF) classification algorithm revealed a species overall classification error
Summary
Methionine metabolism arises as a key target to elucidate the molecular adaptations underlying animal longevity due to the negative association between longevity and methionine content. The metabolites detected and quantified were: (1) methionine and its related metabolites, including the intermediates of the transmethylation pathway Sadenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine; betaine as metabolites involved in the regeneration of methionine plasma levels; the intermediates of the transsulfuration pathway cysteine and cystathionine; taurine and glutathione as downstream metabolites of the transsulfuration pathway; and vitamin B6 metabolites pyridoxal and pyridoxamine, as cofactors of the transsulfuration enzymes; (2) additional amino acids including eight non-polar amino acids (alanine, glycine, leucine, isoleucine, phenylalanine, proline, tryptophan and valine), four polar uncharged amino acids (asparagine, serine, threonine and tyrosine), two polar negatively charged amino acid (aspartate and glutamate) and two polar positively charged amino acids (arginine and histidine); (3) TCA cycle metabolites, including pyruvate, citrate, α-ketoglutarate, succinate, fumarate and malate; and (4) methionine-derived lipid intermediates, such as choline and carnitine. The plasma metabolites profile was determined using a LC-MS/MS platform to define specific phenotypic profiles associated with animal longevity
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