Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness

Abstract

Some of the most serious consequences of ageing are its effects on skeletal muscle. The term ‘sarcopenia’ describes the slow but progressive loss of muscle mass with advancing age and is characterised by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength. The loss of muscle mass and strength is thought to be attributed to the progressive atrophy and loss of individual muscle fibres associated with the loss of motor units, and a concomitant reduction in muscle ‘quality’ due to the infiltration of fat and other non-contractile material. These age-related changes in skeletal muscle can be largely attributed to the complex interaction of factors affecting neuromuscular transmission, muscle architecture, fibre composition, excitation–contraction coupling, and metabolism. Given the magnitude of the growing public health problems associated with sarcopenia, there is considerable interest in the development and evaluation of therapeutic strategies to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness. The aim is to review our current understanding of some of the cellular and molecular mechanisms responsible for age-related changes in skeletal muscle.

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Acknowledgements

Supported by research grant funding from the Australian Research Council Discovery-Project funding scheme (DP0665071, DP0772781), the National Health and Medical Research Council of Australia (350439, 454561, 509313), the Muscular Dystrophy Association (USA, 3595, 4167), the Rebecca L. Cooper Medical Research Foundation, and Pfizer Inc. (USA).

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Correspondence to Gordon S. Lynch.

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Ryall, J.G., Schertzer, J.D. & Lynch, G.S. Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology 9, 213–228 (2008). https://doi.org/10.1007/s10522-008-9131-0

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Keywords

  • Cytokines
  • IGF-I
  • Sarcopenia
  • Satellite cells
  • Myogenic regulatory factors
  • Myostatin
  • Notch