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      Effects of Exercise and Aging on Skeletal Muscle

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          Abstract

          A substantial loss of muscle mass and strength (sarcopenia), a decreased regenerative capacity, and a compromised physical performance are hallmarks of aging skeletal muscle. These changes are typically accompanied by impaired muscle metabolism, including mitochondrial dysfunction and insulin resistance. A challenge in the field of muscle aging is to dissociate the effects of chronological aging per se on muscle characteristics from the secondary influence of lifestyle and disease processes. Remarkably, physical activity and exercise are well-established countermeasures against muscle aging, and have been shown to attenuate age-related decreases in muscle mass, strength, and regenerative capacity, and slow or prevent impairments in muscle metabolism. We posit that exercise and physical activity can influence many of the changes in muscle during aging, and thus should be emphasized as part of a lifestyle essential to healthy aging.

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          Most cited references118

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          Decline in skeletal muscle mitochondrial function with aging in humans.

          Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18-89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly.
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            Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view.

            The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission results in deterioration of mitochondrial bioenergetics. While fusion may benefit mitochondrial function by allowing the spreading of metabolites, protein and DNA throughout the network, the functional benefit of fission is not as intuitive. Remarkably, studies that track individual mitochondria through fusion and fission found that the two events are paired and that fusion triggers fission. On average each mitochondrion would go though approximately 5 fusion:fission cycles every hour. Measurement of Deltapsi(m) during single fusion and fission events demonstrates that fission may yield uneven daughter mitochondria where the depolarized daughter is less likely to become involved in a subsequent fusion and is more likely to be targeted by autophagy. Based on these observations we propose a mechanism by which the integration of mitochondrial fusion, fission and autophagy forms a quality maintenance mechanism. According to this hypothesis pairs of fusion and fission allow for the reorganization and sequestration of damaged mitochondrial components into daughter mitochondria that are segregated from the networking pool and then becoming eliminated by autophagy.
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              Mitochondrial fission and remodelling contributes to muscle atrophy.

              Mitochondria are crucial organelles in the production of energy and in the control of signalling cascades. A machinery of pro-fusion and fission proteins regulates their morphology and subcellular localization. In muscle this results in an orderly pattern of intermyofibrillar and subsarcolemmal mitochondria. Muscular atrophy is a genetically controlled process involving the activation of the autophagy-lysosome and the ubiquitin-proteasome systems. Whether and how the mitochondria are involved in muscular atrophy is unknown. Here, we show that the mitochondria are removed through autophagy system and that changes in mitochondrial network occur in atrophying muscles. Expression of the fission machinery is per se sufficient to cause muscle wasting in adult animals, by triggering organelle dysfunction and AMPK activation. Conversely, inhibition of the mitochondrial fission inhibits muscle loss during fasting and after FoxO3 overexpression. Mitochondrial-dependent muscle atrophy requires AMPK activation as inhibition of AMPK restores muscle size in myofibres with altered mitochondria. Thus, disruption of the mitochondrial network is an essential amplificatory loop of the muscular atrophy programme.
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                Author and article information

                Journal
                Cold Spring Harb Perspect Med
                Cold Spring Harb Perspect Med
                cshperspectmed
                cshperspectmed
                Cold Spring Harbor Perspectives in Medicine
                Cold Spring Harbor Laboratory Press (Cold Spring Harbor, New York )
                2157-1422
                March 2018
                : 8
                : 3
                : a029785
                Affiliations
                [1 ]Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804
                [2 ]Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827
                Author notes
                Article
                PMC5830901 PMC5830901 5830901 a029785
                10.1101/cshperspect.a029785
                5830901
                28432116
                7f1ec276-8bf9-43c1-8925-1aa11fdacbfb
                Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved
                History
                Page count
                Pages: 15
                Categories
                126
                Perspectives

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