Mitochondrial Aging and Physical Decline: Insights From Three Generations of Women

Sadie L. Hebert, Perrine Marquet-De Rougé, Ian R. Lanza, Shelly K. McCrady-Spitzer, James A. Levine, Sumit Middha, Rickey E. Carter, Katherine A. Klaus, Terry M. Therneau, Edward W. Highsmith, K. Sreekumaran Nair

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Decline in mitochondrial DNA (mtDNA) copy number, function, and accumulation of mutations and deletions have been proposed to contribute to age-related physical decline, based on cross sectional studies in genetically unrelated individuals. There is wide variability of mtDNA and functional measurements in many population studies and therefore we assessed mitochondrial function and physical function in 18 families of grandmothers, mothers, and daughters who share the same maternally inherited mtDNA sequence. A significant age-related decline in mtDNA copy number, mitochondrial protein expression, citrate synthase activity, cytochrome c oxidase content, and VO2 peak were observed. Also, a lower abundance of SIRT3, accompanied by an increase in acetylated skeletal muscle proteins, was observed in grandmothers. Muscle tissue-based full sequencing of mtDNA showed greater than 5% change in minor allele frequency over a lifetime in two locations, position 189 and 408 in the noncoding D-loop region but no changes were noted in blood cells mtDNA. The decline in oxidative capacity and muscle function with age in three generations of women who share the same mtDNA sequence are associated with a decline in muscle mtDNA copy number and reduced protein deacetylase activity of SIRT3.

Original languageEnglish (US)
Pages (from-to)1409-1417
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume70
Issue number11
DOIs
StatePublished - Nov 2015

Keywords

  • Acetylated protein
  • Aging
  • Mitochondrial DNA
  • Oxidative capacity
  • SIRT3
  • Skeletal muscle

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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