Greater Mitochondrial Fragmentation Correlates with Loss of Muscle Function
Every cell contains hundreds of mitochondria, descended from ancient symbiotic bacteria. Mitochondrial dynamics are like those of bacteria, in that they constantly divide, fuse together, and swap component parts. Mitochondria are vital to cell function, their primary purpose being to manufacture the chemical energy store molecule adenosine triphosphate (ATP) that powers cell processes. The balance between fission and fusion of mitochondria is known to alter with age, and imbalance generates inflammation and is associated with loss of mitochondrial function. In tissues that require a great deal of energy, such as muscle, mitochondrial dysfunction is likely important in age-related declines.
Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals.
Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle-aged: 99 ± 27 pmol O2/s/mg) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle-aged: 5.68 ± 1.48%), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle-aged: 1.55 ± 0.15 A.U.), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle-aged: 13.55 ± 4.10%) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle-aged: 13.92 ± 4.95%). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density.
Collectively, our work highlights the critical role of skeletal muscle mitochondria in age-associated declines in physical function.