title: Mitochondrial Aging and Physical Decline: Insights From Three Generations of Women.
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.
authors: Mayo Clinic, Division of Endocrinology and.
authors: Sadie L
authors: SL
authors: Hebert
authors: Mayo Clinic, Division of Endocrinology and.
authors: Perrine
authors: P
authors: Marquet-de Rougé
authors: Mayo Clinic, Division of Endocrinology and.
authors: Ian R
authors: IR
authors: Lanza
authors: Mayo Clinic, Division of Endocrinology and.
authors: Shelly K
authors: SK
authors: McCrady-Spitzer
authors: Mayo Clinic, Division of Endocrinology and.
authors: James A
authors: JA
authors: Levine
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, 200 First Street SW, Joseph 5-194, Rochester, Minnesota 55905.
authors: Sumit
authors: S
authors: Middha
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, 200 First Street SW, Joseph 5-194, Rochester, Minnesota 55905.
authors: Rickey E
authors: RE
authors: Carter
authors: Mayo Clinic, Division of Endocrinology and.
authors: Katherine A
authors: KA
authors: Klaus
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, 200 First Street SW, Joseph 5-194, Rochester, Minnesota 55905.
authors: Terry M
authors: TM
authors: Therneau
authors: Mayo Clinic, Division of Endocrinology and.
authors: Edward W
authors: EW
authors: Highsmith
authors: Mayo Clinic, Division of Endocrinology and nair.sree@mayo.edu.
authors: K Sreekumaran
authors: KS
authors: Nair
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D004272:DNA, Mitochondrial / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D057185:Sedentary Behavior; D017422:Sequence Analysis, DNA; D056566:Sirtuin 3 / Q000378:metabolism; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: Acetylated protein; Aging; Mitochondrial DNA; Oxidative capacity; SIRT3; Skeletal muscle