Structure-function relationship and plasticity in old mouse muscle

Ballak, Samson Ben (2015) Structure-function relationship and plasticity in old mouse muscle. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Age-related muscle wasting and weakness (sarcopenia) ultimately lead to a dependent lifestyle. The relative contribution of myofibre loss, atrophy and reduced myofibre function to the age-related decline in muscle function is, however, unknown. Resistance exercise is an effective means to enhance muscle strength via muscle hypertrophy, but the hypertrophic response may be attenuated at old age. Therefore, the overall aim of this PhD-project was to examine the factors that contribute to the impaired muscle function and attenuated hypertrophic response in old age. To investigate this we assessed plantaris muscle function in vivo in adult (9-month-old) and old mice (25-month-old). An additional group of old mice received 0.4% resveratrol. To determine the hypertrophic response we overloaded one plantaris muscle, while the contra-lateral muscle served as internal control. This thesis identified a reduction in specific force, rather than myofiber atrophy and myofiber loss, as the main contributor to the age-related muscle weakness in a model representing the onset of sarcopenia. The reduced specific force was partly explained by an increase in intramuscular connective tissue. At the same time, it was observed that aged muscle also developed hypertrophy in response to chronic overload, although less so than in adult muscle. The blunted hypertrophic response in old muscle was associated with a lower SC density and impaired angiogenesis, but there was no evidence for a lower SC proliferation capacity. Resveratrol did not ameliorate muscle weakness or rescue the hypertrophic response, but even reduced the number of SCs in hypertrophic muscles. Finally, a literature study illustrated that effects of ageing on determinants of muscle force showed qualitatively the same patterns as observed in men. This overview showed that to translate data gained in rodent models of muscle ageing to humans, it is important to correct for relative ages. In conclusion, although with increasing age loss of muscle mass and function do take place, the capacity of muscle to adapt to overload, although weakened, remains until old age. This plasticity of muscles provides hope that exercise interventions are effective into old age and may be implemented to attenuate or even reverse the increased dependent life style and hence improve the quality of life in aged people. The side effect would be a decreased burden on healthcare systems.