Several factors are known to contribute to sarcopenia (Fig.1) but amongst these, neuroendocrine changes are commonly regarded as primary drivers of this process. These are responsible for degeneration of a-motoneurons and of the neuromuscular junction (NMJ) and for muscle fibre denervation, also fuelled by mitochondrial dysfunction and oxidative damage at the NMJ, leading to a loss of motor units and muscle weakness. In fact, one of the crucial systems severely affected in aging is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. There is now growing evidence that cross-talk between muscle and nerve via anterograde/retrograde axonal transport influences motoneuron survival, NMJ integrity, motor unit number and muscle fibre phenotypic, metabolic and functional characteristics. Several neurotrophic and myotrophic factors have indeed been found to orchestrate these changes and many of these, such as brain-derived neurotrophic factor (BDNF) and insulin like growth factor (IGF-1) have potent neuroprotective and myotrophic effects and are modulated by physical activity and nutrition.
It is well established that sarcopenia can be markedly mitigated through strength training (provided a sufficient training volume is used to overcome the anabolic resistance to training typical of old age) but what seems novel and particularly exciting is the observation that the practice of regular physical activity, such as running, seems to protect from neuromuscular degeneration. Recent neurophysiological studies indeed report no decline in motor units in the lower limb muscles of master runners (MA) compared to old sedentary individuals., Indeed, muscle peak power (PP) of MA is, at any given age, greater than that of sedentary CTRL, to the extent that at the age of 70 years PP of MA is comparable to that of CTRL in their 40’s. Furthermore, the regular physical activity of MA seems to preserve muscle architecture from age-related changes associated with sarcopenia, as values of fibre length and pennation angle of the knee extensors are not different from those of young CTRL.
It is not clear how physical activity affords protection against motor unit loss but this could be due to a reduction of inflammation in response to regular physical activity and also by preservation of the neurotrophic and myotrophic actions on motoneurons and on the NMJ.
(Supported by EU FP7 grant 223576, project Myoage)