Age-related skeletal muscle dysfunction: causes and mechanisms.

Age-related muscle weakening may ultimately result in the transition from an independent to a dependent life-style. The decline in muscle strength is larger than expected from the loss of muscle mass. Single fibre studies and in vitro motility assays indicate that part of the muscle dysfunction is due to modifications of the myosin molecule. A lower rate of protein turnover may increase the chance of post-translational modifications such as oxidation and glycation. The impaired regenerative capacity of old muscles is related to a lower differentiation capacity of myosatellite cells, which is most likely due to altered transcriptional activity of myogenic regulatory factors (MRFs). However, old myosatellite cells can be rejuvenated when exposed to serum from young individuals. This indicates that alterations in the environment of the satellite cells or circulating substances play an important role in impaired differentiation capacity of satellite cells in old age. It is proposed that systemic inflammation may be that factor. Indeed, the inflammatory cytokine tumour necrosis factor-alpha: 1) impairs transcriptional regulation by MRFs, 2) suppresses myosatellite cell differentiation and 3) induces apoptosis. Moreover, muscle mass, strength and the response to strength training in old age are all inversely related to the degree of systemic inflammation.