Decline in skeletal muscle mitochondrial function with aging in humans.
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.
Short
Kevin R
KR
Endocrine Research Unit and Department of Laboratory Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Bigelow
Maureen L
ML
Kahl
Jane
J
Singh
Ravinder
R
Coenen-Schimke
Jill
J
Raghavakaimal
Sreekumar
S
Nair
K Sreekumaran
KS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006262:Health; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*; D012313:RNA / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D000077278:RNA, Mitochondrial
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase; D003849:Deoxyguanosine