Longitudinal Neuromuscular and Metabolic Changes With Aging

Ageing is characterized by a decline in neuromuscular control and a progressive loss of muscle mass, strength and power, leading to reduced mobility, loss of independence, higher hospitalizations rate, and increased all-cause mortality. Several studies suggest a non-linear decay of these age-related changes. Denervation-reinnervation processes, resulting in fewer but larger surviving motor units in advanced age, start as early as age 50-60yr and can be magnified in older adults (\>75yr). Significant functional consequences in daily living activities are not usually observed until approximately 50yr. However, after 50yr, muscle strength/power reduction is accelerated and becomes faster than average muscle mass loss. Most observations come from cross- sectional studies and several confounding factors associated with secondary aging, such as physical activity levels, may contribute to (or compensate for) the observed age-related reductions in neuromuscular function. Compared to cross-sectional designs, prospective ones are advantageous in their ability to investigate fundamental mechanisms by excluding inter-subjects variability. In this project, the investigators will characterize longitudinal age-related changes in motor function, physical performance and muscle aerobic metabolism with an integrated approach. The investigators aim to combine classical methods of in-vivo and ex-vivo evaluation of neuromuscular function with innovative approaches for assessing changes and interactions between neural, structural and metabolic variables in two critical phases of ageing: 55-60yrs and 75-80yrs. Within each age-group, subjects will be classified based on their functional capabilities and divided in either active or sedentary. The investigators will describe the 2-yr time course of 1) mechanisms impairing neuromuscular function (denervation-reinnervation processes); 2) interactions between muscle structural changes and neural/metabolic impairments; 3) functional and metaboli