Effects of Aging and Methionine Restriction on Rat Kidney Metabolome

Abstract

Methionine restriction (MetR) in animal models extends maximum longevity and seems to promote renoprotection by attenuating kidney injury. MetR has also been proven to affect several metabolic pathways including lipid metabolism. However, there is a lack of studies about the effect of MetR at old age on the kidney metabolome. In view of this, a mass spectrometry-based high-throughput metabolomic and lipidomic profiling was undertaken of renal cortex samples of three groups of male rats—An 8-month-old Adult group, a 26-month-old Aged group, and a MetR group that also comprised of 26-month-old rats but were subjected to an 80% MetR diet for 7 weeks. Additionally, markers of mitochondrial stress and protein oxidative damage were analyzed by mass spectrometry. Our results showed minor changes during aging in the renal cortex metabolome, with less than 59 differential metabolites between the Adult and Aged groups, which represents about 4% of changes in the kidney metabolome. Among the compounds identified are glycerolipids and lipid species derived from arachidonic acid metabolism. MetR at old age preferentially induces lipid changes affecting glycerophospholipids, docosanoids, and eicosanoids. No significant differences were observed between the experimental groups in the markers of mitochondrial stress and tissue protein damage. More than rejuvenation, MetR seems to induce a metabolic reprogramming.