Decline in skeletal muscle mitochondrial function with aging in humans

TLDR

Accumulating mtDNA damage and mutations are linked to accelerated aging in animals. The study examined whether aging increases DNA oxidative damage and decreases mtDNA abundance and mitochondrial function in human skeletal muscle. In 146 adults aged 18–89, mtDNA and mRNA levels, mitochondrial ATP production, and several mitochondrial proteins declined with age, while oxidative DNA damage increased, linking reduced mtDNA to impaired mitochondrial function, aerobic capacity, and glucose tolerance.

Abstract

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.