Aging of the Neuromuscular System: What Are the Causes of Age-Related Loss of Strength and Muscle Mass, and Can We Prevent Its Development and Progression?

When we grow old, we experience loss of muscle strength and power, a condition commonly referred to as sarcopenia (ICD-10-CM code (M62.84)). Sarcopenia leads to disability in 5-10% of the population. In this review we emphasise that it is not a sudden event, but a deterioration that occurs over time but is only recognised as a disease when it becomes clinically manifest in the 6th-7th decade of life. Evidence from animal studies, elite athletes and longitudinal population studies all confers that once sarcopenia is manifested, the underlying process has been ongoing for decades. We present various hypotheses about the underlying cause(s) of this process and their supporting evidence, i.e. does this disease have a neurogenic, a myogenic or a scaffold-related origin? We briefly review various proposals to alleviate sarcopenia, including stem cell rejuvenation, combating scaffold degeneration, reducing senescent cell burden, skeletal muscle secretomes and muscle innervation. We conclude that although there are potential target candidates and ongoing preclinical and clinical trials with drug treatments, the only evidence-based intervention today is exercise. We present different execrcise programmes and discuss to what extent the inter-individual susceptibility to developing sarcopenia is due to our genetic predisposition or lifestyle factors.