Plasma methionine metabolic profile is associated with longevity in mammals

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.

Methionine metabolism is down-regulated in heart of long-lived mammals

“…Signi cantly, different ndings seem to indicate that the compositional observation at protein level can be extended to the free methionine form. Thus, available evidences related to free methionine and longevity demonstrate lower concentrations of free plasma methionine in long-lived species [47] and exceptionally longevous animal species like naked-mole rat [17,42]. In this context, our study reported the existence of a species-speci c tissue (heart) pro les and association with longevity for metabolites belonging to the methionine metabolism.…”

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

“…Significantly, different findings seem to indicate that the compositional observation at the protein level can be extended to the free methionine form. Thus, available evidence related to free methionine and longevity demonstrates lower concentrations of free plasma methionine in long-lived species [ 23 ] and exceptionally longevous animal species like the naked mole rat [ 19 , 36 ]. In this context, our study reported the existence of species-specific tissue (heart) profiles and association with longevity for metabolites belonging to methionine metabolism.…”

“…Heart metabolite extraction was performed based on a previously described method [ 23 ]. Briefly, 10 µL of sample homogenates were added to 30 µL of cold methanol containing 1 μg/mL of Phe- 13 C as an internal standard and 1 μM BHT as an antioxidant.…”

“…The individual conditions for the detection and quantification of heart metabolites are listed in Table A1 ( Appendix A ). For non-sulphur-containing metabolites, 2 µL of extracted sample was injected based on the method described [ 23 ]. Chromatographic separation was achieved on a reversed-phase column (Zorbax SB-Aq 2.1 × 50 mm, 1.8 µm particle size, Agilent Technologies, Barcelona, Spain) equipped with a pre-column (Zorba-SB-C8 Rapid Resolution Cartridge, 2.1 × 30 mm, 3.5 µm particle size, Agilent Technologies, Barcelona, Spain) with a column temperature of 60 °C.…”

One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

“…Genetic manipulations leading to methionine restriction yield similar results [ 56 , 57 , 58 , 69 ]. Interestingly, a comparative study of plasma methionine metabolic profile among 11 mammalian species whose lifespans range from 3.5 to 120 years revealed a correlation of longevity with reduced methionine and cystathionine levels [ 106 ]. Methionine restriction (MR) is proposed to reproduce some of the metabolic consequences of CR.…”