Antonio Musarò Laboratory

We study muscle homeostasis and regeneration under normal and pathologic conditions. The main goal of our project is to define the tissue signals and to characterize the molecular mechanisms of muscle wasting. Although considerable information has accumulated regarding the physiopathology of muscle diseases, the associated molecular mechanisms are still poorly understood. It is generally accepted that the primary cause of functional impairment in different myopathy is a cumulative failure to repair damage, resulting from sustained muscular activity, related to an overall decrease in anabolic processes. The skeletal musculature is particularly susceptible to the effects of aging and diseases, undergoing a steady reduction in function and losing up to a third of its mass and strength. This decline in mass and functional performance is due to an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue, and marked changes occur in muscle fiber composition, with a characteristic loss in the fastest most powerful fibers. Despite numerous theories and intensive research, the principal molecular mechanisms underlying the process of muscle wasting are still unknown.

Current data point out that the development of muscle wasting is a multifactorial process and believed to be the result of both intrinsic factors, involving changes in molecular and cellular levels, and extrinsic ones, such as nutrition and exercise. Many factors, including motor-unit remodelling, decreased hormone levels with consequent negative effect on protein synthesis, stress oxidative damage, alteration in satellite cells activity may all contribute to decrease in muscle mass and functional performance.

The achievement of this project will allow us to design therapeutic approaches to preserve the heterogeneity, the strength and the architecture of muscle fibers in degenerative pathology associated with muscle wasting.

Our approach to these goals entails both hypothesis-driven and data-driven investigations and combines an interdisciplinary set of expertise, ranging from cell, molecular, and biochemical tools to animal models, tissue engineering, material science and bio-mechanics approaches.