Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice

Adam B. Salmon, Geumsoo Kim, Chengyu Liu, Jonathan D. Wren, Constantin Georgescu, Arlan Richardson, Rodney L. Levine

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA) repairs oxidation of free- and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria. Previous studies in Drosophila have shown that increasing expression of MsrA can extend longevity. Here we test the effects of increasing MsrA on longevity and healthy aging in two transgenic mouse models. We show that elevated expression of MsrA targeted specifically to the cytosol reduces the rate of age-related death in female mice when assessed by Gompertz analysis. However, neither cytosolic nor mitochondrial MsrA overexpression extends lifespan when measured by log-rank analysis. In mice with MsrA overexpression targeted to the mitochondria, we see evidence for improved insulin sensitivity in aged female mice. With these and our previous data, we conclude that the increasing MsrA expression in mice has differential effects on aging and healthy aging that are dependent on the target of its subcellular localization.

Original languageEnglish (US)
Pages (from-to)251-256
Number of pages6
JournalRedox Biology
Volume10
DOIs
StatePublished - Dec 1 2016

Keywords

  • Longevity
  • Metabolism
  • Oxidative stress
  • Proteostasis
  • Redox

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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