The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging
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- Michael E. Walsh
- Department of Cellular and Structural Biology San Antonio TX 78229
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- Arunabh Bhattacharya
- Department of Cellular and Structural Biology San Antonio TX 78229
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- Kavithalakshmi Sataranatarajan
- Oklahoma Medical Research Foundation Oklahoma City OK USA
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- Rizwan Qaisar
- Oklahoma Medical Research Foundation Oklahoma City OK USA
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- Lauren Sloane
- The Barshop Institute for Longevity and Aging Studies, San Antonio, TX 78245 The University of Texas Health Science Center at San Antonio TX 78229 USA
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- Md M. Rahman
- Department of Cellular and Structural Biology San Antonio TX 78229
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- Michael Kinter
- Oklahoma Medical Research Foundation Oklahoma City OK USA
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- Holly Van Remmen
- Oklahoma Medical Research Foundation Oklahoma City OK USA
説明
<jats:title>Summary</jats:title><jats:p>Sarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with loss of motor neuron innervation, we investigated the potential for the histone deacetylase (<jats:styled-content style="fixed-case">HDAC</jats:styled-content>) inhibitor butyrate to modulate age‐related muscle loss. Consistent with previous studies, we found significant loss of hindlimb muscle mass in 26‐month‐old C57Bl/6 female mice fed a control diet. Butyrate treatment starting at 16 months of age wholly or partially protected against muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross‐sectional area and prevented intramuscular fat accumulation in the old mice. In addition to the protective effect on muscle mass, butyrate reduced fat mass and improved glucose metabolism in 26‐month‐old mice as determined by a glucose tolerance test. Furthermore, butyrate increased markers of mitochondrial biogenesis in skeletal muscle and whole‐body oxygen consumption without affecting activity. The increase in mass in butyrate‐treated mice was not due to reduced ubiquitin‐mediated proteasomal degradation. However, butyrate reduced markers of oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data is the first to show a beneficial effect of butyrate on muscle mass during aging and suggests <jats:styled-content style="fixed-case">HDAC</jats:styled-content>s contribute to age‐related muscle atrophy and may be effective targets for intervention in sarcopenia and age‐related metabolic disease.</jats:p>
収録刊行物
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- Aging Cell
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Aging Cell 14 (6), 957-970, 2015-08-20
Wiley