Arguing for Exercise to be a Useful Treatment for Sarcopenia Because it Affects Mitochondria, Unlike Most Other Attempted Interventions

In this open access paper, the authors argue that exercise (and particularly strength training) remains the best therapy for sarcopenia, the age-related loss of muscle mass and strength, because exercise improves mitochondrial function and other attempted treatments do not. This seems a reasonable position. There are many, many possible contributing causes of sarcopenia, all with accompanying evidence, but the most compelling in my opinion is stem cell dysfunction. Even so, one still needs to offer an explanation as to why exactly stem cell activity in muscle tissue declines with age, a way to link it to the root cause molecular damage of aging listed in the SENS research proposals. Perhaps faltering mitochondrial function is a noteworthy underlying cause.

Resistance exercise continues to be the most effective intervention against sarcopenia. In addition, maintenance of physical activity can delay the progression of sarcopenia. Despite the strong support for maintaining an active lifestyle, adherence to physical activity guidelines remains low. The traditional therapeutic focus of sarcopenia treatment is to target growth-related pathways to increase muscle mass. Here, we discuss the positives of these strategies, but also build a case for targeting mitochondrial bioenergetics as a way to maintain muscle mass and function with age.

The vast majority of adults fail to meet physical activity guidelines. While 60% of adults, both European and American, self-report that they meet guidelines, objectively measured physical activity reveals that fewer than 10% of adults in the United States meet physical activity guidelines. Moreover, sedentary behavior alone increases the risk for sarcopenia. While there are few trials in humans on the effects of lifelong sedentary behavior, studies in mice reveal lifelong sedentary behavior impairs mitochondrial function.

It was thought that resistance exercise training had little or no effect on mitochondrial biogenesis or function. However, recent studies have shown that resistance exercise training increases mitochondrial protein fractional synthesis rates (FSRs) and improves mitochondrial function. Young adults engaged in a resistance exercise program showed increases in mitochondrial enzyme activity and respiration. While the changes in mitochondrial respiration are modest in comparison to endurance exercise, improvements in in vivo phosphocreatine recovery rates and oxidative capacity appear comparable in older adults engaged in either exercise intervention.

Aerobic exercise is generally not appreciated as a stimulator of hypertrophy; however, there is evidence that it can lead to muscle hypertrophy. Nearly half a century ago, it was first documented that aerobic exercise increases mitochondrial content. Since then, research has consistently documented that aerobic exercise improves both mitochondrial content and function. Aerobic exercise increases mitochondrial turnover since it increases both mitochondrial biogenesis (protein synthesis) and mitophagy (mitochondrial-specific autophagy). The improvement in the rate of ATP production from aerobic exercise training suggests that more energy is available to maintain proteostasis. Additionally, improvement in mitochondrial efficiency (reduction in ROS generated per oxygen consumed or ATP generated) suggests that there is less oxidative stress and damage, which would in turn improve the quality of the proteome. In all, aerobic exercise mediated improvements in mitochondrial function likely protects against sarcopenia.