TY - JOUR
T1 - Decline in skeletal muscle mitochondrial function with aging in humans
AU - Short, Kevin R.
AU - Bigelow, Maureen L.
AU - Kahl, Jane
AU - Singh, Ravinder
AU - Coenen-Schimke, Jill
AU - Raghavakaimal, Sreekumar
AU - Nair, K. Sreekumaran
PY - 2005/4/12
Y1 - 2005/4/12
N2 - 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.
AB - 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.
KW - Mitochondrial proteins
KW - Oxidative damage
KW - Sarcopenia
KW - mRNA
KW - mtDNA
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U2 - 10.1073/pnas.0501559102
DO - 10.1073/pnas.0501559102
M3 - Article
C2 - 15800038
AN - SCOPUS:17244363631
SN - 0027-8424
VL - 102
SP - 5618
EP - 5623
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -