Decline in skeletal muscle mitochondrial function with aging in humans

Kevin R. Short, Maureen L. Bigelow, Jane Kahl, Ravinder Jit Singh, Jill Coenen-Schimke, Sreekumar Raghavakaimal, K Sreekumaran Nair

Research output: Contribution to journalArticle

612 Citations (Scopus)

Abstract

Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18-89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly.

Original languageEnglish (US)
Pages (from-to)5618-5623
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number15
DOIs
StatePublished - Apr 12 2005

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Mitochondrial DNA
Skeletal Muscle
Muscles
Adenosine Triphosphate
Deoxyguanosine
Mitochondrial Proteins
DNA Damage
Glucose
Mutation
DNA

Keywords

  • Mitochondrial proteins
  • mRNA
  • mtDNA
  • Oxidative damage
  • Sarcopenia

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Decline in skeletal muscle mitochondrial function with aging in humans. / Short, Kevin R.; Bigelow, Maureen L.; Kahl, Jane; Singh, Ravinder Jit; Coenen-Schimke, Jill; Raghavakaimal, Sreekumar; Nair, K Sreekumaran.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 15, 12.04.2005, p. 5618-5623.

Research output: Contribution to journalArticle

Short, Kevin R. ; Bigelow, Maureen L. ; Kahl, Jane ; Singh, Ravinder Jit ; Coenen-Schimke, Jill ; Raghavakaimal, Sreekumar ; Nair, K Sreekumaran. / Decline in skeletal muscle mitochondrial function with aging in humans. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 15. pp. 5618-5623.
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