Mitochondrial thioredoxin reductase 2 is elevated in long-lived primate as well as rodent species and extends fly mean lifespan

Andrew M. Pickering, Marcus Lehr, Christi M. Gendron, Scott D. Pletcher, Richard A. Miller

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In a survey of enzymes related to protein oxidation and cellular redox state, we found activity of the redox enzyme thioredoxin reductase (TXNRD) to be elevated in cells from long-lived species of rodents, primates, and birds. Elevated TXNRD activity in long-lived species reflected increases in the mitochondrial form, TXNRD2, rather than the cytosolic forms TXNRD1 and TXNRD3. Analysis of published RNA-Seq data showed elevated TXNRD2 mRNA in multiple organs of longer-lived primates, suggesting that the phenomenon is not limited to skin-derived fibroblasts. Elevation of TXNRD2 activity and protein levels was also noted in liver of three different long-lived mutant mice, and in normal male mice treated with a drug that extends lifespan in males. Overexpression of mitochondrial TXNRD2 in Drosophila melanogaster extended median (but not maximum) lifespan in female flies with a small lifespan extension in males; in contrast, overexpression of the cytosolic form, TXNRD1, did not produce a lifespan extension.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalAging cell
Volume16
Issue number4
DOIs
StatePublished - Aug 2017

Keywords

  • Drosophila
  • TXN
  • TXNRD2
  • Trxr2
  • aging
  • lifespan
  • mice
  • mitochondria
  • oxidative stress
  • primates
  • rodents
  • thioredoxin

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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