A Mitochondrial View of Muscle Aging

The hundreds of mitochondria present in every cell are primarily responsible for generating adenosine triphosphate, a chemical energy store molecule used to power cell operations. Mitochondria are the descendants of ancient symbiotic bacteria, and carry a small circular genome, the mitochondrial DNA. They replicate as needed, can fuse together and swap component parts, and damaged mitochondria are removed by cell maintenance processes. Mitochondrial function declines with age for a variety of reasons that include damage to mitochondrial DNA and changes in the expression of genes involved in replication, fusion, and quality control. How much of a contribution does this make to muscle aging? To determine that will require therapies such as mitochondrial transplantation that can repair the mitochondrial dysfunction of aging without changing other aspects of aged tissues.

Healthy lifestyles, such as those that include regular physical activity and a balanced diet, are a powerful means to prevent chronic disease and age-related functional decline. A common denominator of health improvements resulting from good exercise and diet habits is the optimization of metabolic processes. These processes include energy metabolism and, thus, the activity of mitochondria. Mitochondria represent hubs not only of cellular metabolism but also of the regulation of redox states, inflammatory response, and immunity, as well as many other cellular features. Mitochondria have emerged as highly flexible organelles that, quickly - and sometimes persistently - adapt to changing conditions in response to systemic or cellular challenges. Next to exercise and diets that promote mitochondrial health, transient exposures to environmental stressors, such as to altitude/hypoxia or extreme temperatures, also induce mitochondrial adaptations.

In this paper, we discuss how different systemic and cellular challenges trigger specific and overlapping mitochondrial responses that - under the right conditions - may translate into protective mitochondrial adaptations. We specifically focus on adaptations in skeletal muscle and sarcopenia, the age-related loss of skeletal muscle mass, strength, and function. Such responses rely on mechanisms such as mitochondrial stress responses and quality control; therefore, these mechanisms are believed to be required to maintain mitochondrial health. The resulting adaptations increase the capacity of mitochondria to respond to future stressors (e.g., altered oxygen or substrate availability), which otherwise might trigger pathological processes. Considering potential synergistic/anti-synergistic and complementary/competitive effects among lifestyle factors and environmental challenges on mitochondria, we argue that recommendations can be developed to increase performance, prevent sarcopenia, and improve healthy aging.

Link: https://doi.org/10.3389/fpubh.2023.1330131