Endocrine Abstracts

Aim: We investigated the influence of mitochondrial dysfunction associated with aging on physical performance in mice, and the effect of hormone replacement on physical performance.

Method: Using 8, 20, 50 and 100 week-old C57bl6 mice, we evaluated skeletal muscle mass, mitochondrial activity, glucose tolerance and physical performance (muscle power and exercise endurance). In addition, we treated 50-week-old mice with ghrelin or insulin like growth factor 1 (IGF1), which are representative hormones that are decreased associated with aging, and investigated the effect on physical performance.

Result: Skeletal muscle mass and mitochondrial activity was decreased associated with aging. Muscle mass was decreased drastically between 20- and 50-week-old, and the time-course was paralleled to decrease in muscle power. Mitochondrial activity was diminished continuously from 8- to 100-week-old, and this change was paralleled to decrease in exercise endurance. As regulatory factors of muscle mass and the mitochondrial function, we focused on mammalian target of rapamycin complex1 (TORC1) and AMP-activated protein kinase (AMPK) in muscle, respectively. Activity of TORC1 was diminished with aging in parallel to muscle mass and power, and that of AMPK was paralleled to muscle mitochondrial activity and exercise endurance. The treatment with IGF1 in 50-week-old mice recovered muscle mass and power; however, it did not improved mitochondrial activity or exercise endurance. The treatment with ghrelin recovered not only muscle mass and muscle power; but also mitochondrial activity and exercise endurance, which were deteriorated in aging mice. The ghrelin-induced recovery was associated with dual activation of TORC1 and AMPK in muscle.

Conclusion: Muscle mitochondrial dysfunction was closely associated with decrease in exercise endurance. Ghrelin replacement would be a hopeful strategy for the decrease in physical performance associated with aging.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.