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Decline in skeletal muscle mitochondrial function with aging in humans
Kevin R Short1, Maureen L Bigelow, Jane Kahl
1Endocrine Research Unit and Department of Laboratory Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Summary
Aging leads to decreased mitochondrial DNA (mtDNA) and impaired mitochondrial function in human skeletal muscle. This age-related decline is linked to reduced aerobic capacity and glucose tolerance, supporting the oxidative damage theory of aging.
Area of Science:
- Gerontology
- Mitochondrial Biology
- Skeletal Muscle Physiology
Background:
- Mitochondrial DNA (mtDNA) damage accumulates with age.
- mtDNA mutations can accelerate aging processes in animal models.
- Age-related changes in skeletal muscle mitochondria are not fully understood in humans.
Purpose of the Study:
- To investigate if aging increases DNA oxidative damage in human skeletal muscle.
- To determine if aging reduces mitochondrial DNA (mtDNA) abundance and mitochondrial function in human skeletal muscle.
- To explore the relationship between mtDNA abundance, mitochondrial function, and age-related functional declines.
Main Methods:
- Studied 146 healthy men and women aged 18-89 years.
- Assessed mtDNA and mRNA abundance in skeletal muscle.
- Measured mitochondrial ATP production rate, aerobic capacity, and glucose tolerance.
- Analyzed the content of mitochondrial proteins and levels of 8-oxo-deoxyguanosine (an oxidative DNA lesion).
Main Results:
- mtDNA and mRNA abundance declined with advancing age.
- Mitochondrial ATP production rate decreased in older individuals.
- Reduced mtDNA abundance correlated positively with ATP production, aerobic capacity, and glucose tolerance.
- Older muscles showed reduced mitochondrial protein content and increased 8-oxo-deoxyguanosine levels.
Conclusions:
- Aging is associated with reduced mtDNA abundance and impaired mitochondrial function in human skeletal muscle.
- Age-related mitochondrial dysfunction contributes to decreased aerobic capacity and glucose tolerance.
- Increased oxidative DNA damage (8-oxo-deoxyguanosine) supports the oxidative damage theory of aging in muscle mitochondria.