Age- and tissue-specific changes in mitochondrial and nuclear DNA base excision repair activity in mice: Susceptibility of skeletal muscles to oxidative injury

Bartosz Szczesny, Anne W. Tann, Sankar Mitra

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

In this study, we investigated age- and tissue-dependent changes in the DNA base excision repair (BER) of oxidative lesions in mitochondrial and nuclear extracts by measuring single-nucleotide (SN)- and long-patch (LP)-BER activities in five tissues isolated from 4-, 10- and 20-month-old mice. Age-dependent SN-BER and LP-BER activity was increased in the mitochondria of liver, kidney and heart, but generally decreased in skeletal muscles. In contrast, no significant changes in repair activity were observed in nuclear extracts of the same tissues, except for quadriceps, where the SN-BER activity was higher in the old animals. Moreover, the BER activities in both the nucleus and the mitochondria were significantly lower in skeletal muscles compared to liver or kidney of the same mice. The protein level of three antioxidant enzymes, Mn and Cu/Zn superoxide dismutases (SOD) and catalase, was also significantly lower in skeletal muscle compared to liver or kidney. In addition, we found higher levels of protein carbonylation in the mitochondria of skeletal muscle relative to other tissues. Thus, it appears likely that mouse skeletal muscle is highly susceptible to oxidative stress due to deficiency in both repair of oxidative DNA damage and antioxidant enzymes, contributing to age-dependent muscle loss.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalMechanisms of Ageing and Development
Volume131
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Aging
  • Base excision repair
  • Mitochondria
  • Oxidative stress
  • Sarcopenia

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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