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As outlined above, there is substantial evidence that mitochondrial function in skeletal muscle declines with aging, and that such decline has important functional consequences on mobility performance. We have examined several possible causes of mitochondrial dysfunction with aging, including a progressive decline of physical function, oxidative stress, anabolic resistance, accumulation of somatic mutations, and alterations of mitochondrial quality control mechanisms including proteostasis, fusion/fission, and mitophagy. Although we have attempted to be as comprehensive as possible in our review of the literature, we are fully aware that this chapter cannot exhaustively explore the enormous literature on the complex relationship between mitochondria, skeletal muscle, and aging. For example, there is evidence that part of the decline in muscle strength with aging is due to a dysfunction of neurological control, both at the central and the peripheral level, and mitochondrial aging presumably contributes to this important cause of sarcopenia. Since the neurological prospective to sarcopenia is addressed in another chapter of this book, we are confident that these aspects will not be ignored in this publication.

Importantly, many of the changes in mitochondria described in this chapter occur in the majority of aging individuals, and not only in those who develop sarcopenia. Thus, the question remains: “Is mitochondrial dysfunction the cause of age‐related sarcopenia?”. In spite of extensive and sophisticated research in this field, a solid answer to such question is still lacking. Of course, if the age‐associated changes described here are overt, the structure and function of mitochondria would be damaged with serious consequences on muscle oxidative capacity, and ultimately on the anatomic integrity and the ability to produce contractile force. Arguably, the lack of success in this field is due to a substantial disagreement between investigators about the appropriate definition of sarcopenia (also addressed elsewhere in this book), and to the fact that few studies have performed muscle biopsies in older persons affected by sarcopenia, which is often associated with poor health status and disability. As mentioned earlier, perhaps the best evidence that sarcopenia is associated with poor mitochondrial function is a gene expression study recently conducted in a multiethnic population where transcripts related to sarcopenia were substantially underrepresented in people with sarcopenia compared with controls [10]. In addition, a metabolomic study conducted in a relatively large population found that carnitine, a mitochondrial lipid transporter essential for the entry of fatty acids, potential fuel and synthetic precursors for the mitochondria, as well as vitamin E, a strong antioxidant important for mitochondrial function, are underrepresented in the serum of frail compared to non‐frail individuals [85]. Indeed, randomized controlled trials are currently in the field that target mitochondrial health to prevent sarcopenia. Ultimately, the results of these studies should provide an answer of whether changes in mitochondrial function are the root causes to sarcopenia.