Dataset Information

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.

SUBMITTER: Pradas I

PROVIDER: S-EPMC6918429 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Effects of Aging and Methionine Restriction on Rat Kidney Metabolome.

Pradas Irene I Jové Mariona M Cabré Rosanna R Ayala Victoria V Mota-Martorell Natalia N Pamplona Reinald R

Metabolites 20191114 11

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-mont ...[more]

PMID: 31739579

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Project description:Methionine restriction (MR) extends lifespan in various model organisms, and understanding the molecular effectors of MR could expand the repertoire of tools targeting the aging process. Here, we address to what extent the biochemical pathway responsible for redox metabolism of methionine plays in regulating the effects of MR on lifespan and health span. Aerobic organisms have evolved methionine sulfoxide reductases to counter the oxidation of the thioether group contained in the essential amino acid methionine. Of these enzymes, methionine sulfoxide reductase A (MsrA) is ubiquitously expressed in mammalian tissues and has subcellular localization in both the cytosol and mitochondria. Loss of MsrA increases sensitivity to oxidative stress and has been associated with increased susceptibility to age-associated pathologies including metabolic dysfunction. We rationalized that limiting the available methionine with MR may place increased importance on methionine redox pathways, and that MsrA may be required to maintain available methionine for its critical uses in cellular homeostasis including protein synthesis, metabolism, and methylation. Using a genetic mutant mouse lacking MsrA, we tested the requirement for this enzyme in the effects of MR on longevity and markers of healthy aging late in life. When initiated in adulthood, we found that MR had minimal effects in males and females regardless of MsrA status. MR had minimal effect on lifespan with the exception of wild-type males where loss of MsrA slightly increased lifespan on MR. We also observed that MR drove an increase in body weight in wild-type mice only, but mice lacking MsrA tended to maintain more stable body weight throughout their lives. We also found that MR had greater benefit to males than females in terms of glucose metabolism and some functional health span assessments, but MsrA generally had minimal impact on these metrics. Frailty was also found to be unaffected by MR or MsrA in aged animals. We found that in general, MsrA was not required for the beneficial effects of MR on longevity and health span.

Dataset Information

Effects of Aging and Methionine Restriction on Rat Kidney Metabolome.

Publications

Effects of Aging and Methionine Restriction on Rat Kidney Metabolome.

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