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 we will characterize longitudinal age-related changes in motor function, physical performance and muscle

aerobic metabolism with an integrated approach. We 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. . We 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 metabolic changes occurring at whole muscle as well as single fibers level. The results will extend current understanding of physiological determinants of neuromuscular alterations in aging by identifying the course and rate of changes of specific factors that mediate functional loss and disability in older adults.

Exercise intolerance, defined as the incapacity to produce/maintain adequate muscle force or power to accomplish a task commensurate to the needs of everyday life, represents one of the clinical hallmarks of aging

as well as of many chronic diseases. Consequently, non-invasive methods and tools capable to objectively identify and quantify, the metabolic and functional impairments of the muscle oxidative metabolism

in healthy subjects and patients have become essential. More specifically, methods developed over the years with the aim to identify and evaluate basic physiological mechanisms, and traditionally applied for the

functional evaluation of sport performance, can be utilized, within a translational approach, to better identify the physiological origins of the metabolic impairments. Moreover, the noninvasiveness of these approaches

allows repeated measurements to be performed, allowing the quantification of progression over time. In this project, both submaximal and peak exercise responses will be evaluated through cardiopulmonary exercise

testing (CPET) providing assessment of the integrative responses of pulmonary, cardiovascular, and skeletal muscle systems.

Our group is responsible for the development of the optical innovative technologies for muscle oxidative metabolism determination. The techniques developed are: 1) time domain near infrared spectroscop y(TD NIRS) for determining the concentration of the muscular oxy-, deoxy- and total- hemoglobin and muscle oxygen saturation;2) Diffuse Correlation Spectroscopy (DCS), for the determination of muscle blood flow.