Early-Skeletal Muscle Mitochondrial Impairment Is Associated with Reduced Life Expectancy in Rats with Low Intrinsic Exercise Capacity

Objectives: Aging is associated with decreasing exercise capacity and increasing incidence of cardiovascular diseases. In the model of rats with inherited high (HCR) or low (LCR) intrinsic exercise capacity HCR present with 50% higher life expectancy than LCR. Live expectancy has been linked to intracellular processes such as telomere length. However, mitochondrial role in aging has been scarcely investigated. We thus assessed mitochondrial function in rats differing with high or low aerobic exercise capacity with age.

Methods: HCR and LCR of adult (15 weeks) and old (100 weeks) age as well as senescent (130 weeks) HCR were tested for exercise capacity and cardiac function. Mitochondria from cardiac and skeletal muscle were functionally assessed and oxidative stress determined.

Result: Independent of age, exercise capacity was lower in LCR (HCR old vs. LCR old: 29.5 ± 1.6 vs. 17.1 ± 2.1 m/min). Cardiac function decreased with age but was comparable in HCR and LCR. In skeletal muscle with age, respiratory capacity decreased (HCR adult vs. old: 280 ± 33 vs. 185 ± 13; LCR adult vs. LCR old: 173 ± 12 vs. 100 ± 11 natomsO/min/mg protein). Old LCR presented with lower values compared with old HCR. With senescence HCR showed an additional impairment of mitochondrial respiration (HCR senescent vs. LCR old: 109 ± 11 vs. 100 ± 11 natomsO/min/mg protein) leading to same low levels as found in old LCR. The ratio of exercise capacity to respiratory capacity was higher in adult HCR and increased in old LCR and senescent HCR, indicating increased efficacy in HCR and old animals. Neither mitochondrial ROS production nor oxidative damage indicated differences between HCR and LCR.

Conclusion: Genetic predisposition for low exercise capacity is associated with a decline of skeletal muscle mitochondrial function with age. In contrast, genetic predisposition for high exercise capacity comes with a long maintenance of mitochondrial function.

Publication History

Article published online:
19 February 2021