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Nuclear Apoptosis and Sarcopenia

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Sarcopenia – Age-Related Muscle Wasting and Weakness

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Abstract

Apoptosis is a well-conserve cellular disassembly process, which has been implicated in a variety of diseases. Unlike cells with a single nucleus, apoptotic signaling can target individual nuclei in multi-nucleated skeletal muscle cells without necessarily eliminating the entire cell (muscle fiber). This targeted apoptosis or “nuclear apoptosis” appears to have a role in regulating aging-induced muscle loss (sarcopenia) by reducing the myofiber volume (i.e. cytoplasm) that can be supported in a single muscle fibre. Recent investigations indicate that apoptotic signaling in aged skeletal muscles occurs through three apoptotic pathways. The intrinsic or mitochondria apoptotic pathway has been most widely studied in muscle. Mitochondria dysfunction and increased mitochondria permeability lead to activation of cysteine-aspartic acid proteases (caspases) and eventually DNA fragmentation in sarcopenia. The death receptor (extrinsic) apoptotic pathway has been strongly implicated in sarcopenia and other conditions of muscle loss with aging or disuse. TNF-α is thought to initiate apoptotic signaling via the death receptor, and this can proceed to activate the effort proteases (e.g., caspase 3) independent from mitochondria signaling. Nevertheless, there is some cross-talk between the intrinsic and the extrinsic apoptotic pathways. Finally, a few studies have shown data to suggest that the endoplasmic reticulum-stress apoptotic pathway may also have a role in sarcopenia, although the importance of this pathway relative to the other two pathways is less clear. Both myonuclei and satellite cells appear to be susceptible to nuclear apoptosis in sarcopenia.

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Authors and Affiliations

  1. Department of Exercise Physiology, and Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Robert C Byrd Health Sciences Center, 1 Medical Center Drive, Morgantown, WV, 26506, USA

    Stephen E. Alway

  2. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China

    Parco M. Siu

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    Gordon S. Lynch

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Alway, S.E., Siu, P.M. (2011). Nuclear Apoptosis and Sarcopenia. In: Lynch, G. (eds) Sarcopenia – Age-Related Muscle Wasting and Weakness. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9713-2_9

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