Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 70, Issue 11, Pages 1409-1417Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glv086
Keywords
Mitochondrial DNA; Aging; SIRT3; Oxidative capacity; Acetylated protein; Skeletal muscle
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Funding
- National Institutes of Health [R01 AG09531]
- CTSA from the National Center for Advancing Translational Science (NCATS) [UL1 TR000135]
- Mayo Clinic Metabolomics Resource Core from the National Institute of Diabetes and Digestive and Kidney Diseases [U24DK100469]
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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.
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