Skeletal muscle mitochondria-endoplasmic reticulum contacts (MERCs): impact of aging and exercise

Aging is a condition that afflicts all living things. Finding ways to delay or inhibit this process will undoubtedly improve the human experience. Skeletal muscle is a highly adaptable tissue that is especially prone to age-related decline in mass and function (i.e., sarcopenia). Delaying and/or preventing the loss of skeletal muscle with aging will provide invaluable contributions to extending our health spans, which is the portions of our lives lived in good physical condition. One of the hallmarks of muscle aging is dysfunctional mitochondria. In muscle, these cellular powerhouses are indispensable for initiating and maintaining muscle contractions important for activities such as exercise. Importantly, mitochondria also communicate with other organelles to accomplish their function. Mitochondria-ER contact sites (MERCs) describe the functional pairing of mitochondria and the endo/sarcoplasmic reticulum. MERCs are currently not well-understood in the context of skeletal muscle aging. Therefore, we sought to characterize MERC structure and function in an aging animal model (i.e., mice). We also examined if changes in these contact sites correlate with healthier muscle in trained older mice. Compared to young animals, our older mice demonstrated sarcopenia and showed abnormal mitochondria with aging. This was concomitant with wider and smaller MERCs, suggestive of decreased efficiency. With exercise, the older mice showed dramatic improvements in muscle size and function. This was related to improvements in aspects of mitochondrial function and closer (i.e., narrower) and more numerous MERCs. Overall, our findings suggest that MERCs may play a role in skeletal muscle aging and that they may be partially responsible for adaptations of muscle to chronic exercise.