TY - JOUR
T1 - Mitochondrial Aging and Physical Decline
T2 - Insights From Three Generations of Women
AU - Hebert, Sadie L.
AU - Marquet-De Rougé, Perrine
AU - Lanza, Ian R.
AU - McCrady-Spitzer, Shelly K.
AU - Levine, James A.
AU - Middha, Sumit
AU - Carter, Rickey E.
AU - Klaus, Katherine A.
AU - Therneau, Terry M.
AU - Highsmith, Edward W.
AU - Nair, K. Sreekumaran
N1 - Publisher Copyright:
© 2015 The Author.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
KW - Acetylated protein
KW - Aging
KW - Mitochondrial DNA
KW - Oxidative capacity
KW - SIRT3
KW - Skeletal muscle
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U2 - 10.1093/gerona/glv086
DO - 10.1093/gerona/glv086
M3 - Article
C2 - 26297939
AN - SCOPUS:84946606510
SN - 1079-5006
VL - 70
SP - 1409
EP - 1417
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 11
ER -