Muscle wasting is the progressive loss of skeletal muscle mass caused by immobility, ageing, malnutrition, medications, injuries, or diseases that impact the musculoskeletal or nervous system. Severe muscle loss translates into muscle weakness and frailty, leading to poor quality of life along with increased disability, morbidity and mortality. As a result, muscle wasting is a significant public health burden deeply affecting welfare and healthcare costs.
Recent evidence showed that attenuating muscle wasting in disease conditions ameliorates prognosis and survival; nevertheless, to date a proper strategy to fully and transversally prevent muscle wasting is missing, reflecting the fragmented knowledge of the signals at the basis of the phenomenon. For these reasons, a deeper comprehension of the molecular mechanisms involved will be fundamental for the discovery and characterization of novel potential targets for drug development.
Muscle wasting is indeed a complex phenomenon that involves the activation of several interconnected signaling events and pathways, although not all of them have been sufficiently characterized. With the intention of filling this gap, the project aims to expand the knowledge of the molecular mechanisms controlling muscle homeostasis and to unravel the connection between lysosomal signaling and muscle atrophy.
Therefore, Myo_LysoZOOM main objective has been to investigate the relevance of unknown lysosome-based signals for muscle physiology in healthy and wasting conditions. This has been possible thanks to the development of a new methodology allowing the rapid isolation of lysosomes from fresh tissues that were subsequently profiled for polar metabolites and proteins content in different muscle wasting conditions and at different timepoints. The generated datasets have been at the basis for the identification of the common lysosomal signature impacting muscle mass homeostasis. Interestingly, lysosomal glycolysis has been shown to be fundamental to guarantee key lysosomal processes that are the basis of lysosal homeostasis and function.
In conclusion, the project strongly contributed to the generation of novel knowledge on a complex phenomenon deeply affecting modern society, with the potential of being the basis for new therapies development.
Moreover, through the accomplishment of the action and the establishment of this new research line, Myo_LysoZOOM also fostered Dr. Armani’s scientific and professional growth, that guided the researcher towards a more independent position with the acquiring of independent funding for continuing his own research .
