Skeletal muscle mitochondrial network dynamics in metabolic disorders and aging

• Published in: Trends in molecular medicine 2021-11, Vol.27 (11), p.1033-1044
• Main Authors: Fealy, Ciarán E., Grevendonk, Lotte, Hoeks, Joris, Hesselink, Matthijs K.C.
• Format: Article
• Language: English
• Subjects: Aged; aging; Aging - pathology; Humans; metabolic disease; Metabolic Diseases - metabolism; mitochondria; Mitochondrial Dynamics; Muscle, Skeletal - metabolism; sarcopenia; Sarcopenia - metabolism
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2021.07.013

With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data. We highlight some of the areas where more data are needed to identify the specific mechanisms connecting mitochondrial morphology and skeletal muscle dysfunction. Global demographics suggest an aging population, prompting concerns about an increase in the numbers of individuals with an age-associated loss of independence.Increasing adiposity is a risk factor for skeletal muscle insulin resistance, metabolic disease, and loss of skeletal muscle mass and function.Mitochondrial dynamics may be a therapeutic target for disorders of aging with an increasing number of studies suggest the presence of altered mitochondrial morphology in aging and obesity.Mitochondrial fragmentation is associated with metabolic disease development, while mitochondrial autophagy may be dysregulated in loss of muscle mass and strength.There remain significant gaps in the literature; however, the development of novel methodologies is facilitating a better understanding of mitochondrial network dynamics in age- and obesity- associated skeletal muscle dysfunction.