How is the muscle fiber type profile established during development and modified during aging and in response to physiological and pathological stimuli? What are the signaling pathways that control muscle fiber type and fiber size?
During development skeletal muscle fibers undergo a process of growth and diversification into different fiber types which is dependent on innervation. Adult muscle fibers can undergo further changes in fiber size (atrophy and hypertrophy) and fiber type (fast-slow fiber switching) in a variety of physiological and pathological conditions, such as exercise and disuse. The dissection of the signaling pathways that control muscle fiber size and type is essential to identify novel approaches to prevent muscle wasting during aging and chronic diseases.
Our lab has developed a battery of monoclonal ant-myosin heavy chain antibodies that are widely used to distinguish muscle fiber types in rodent and human skeletal muscle. We have identified a distinct type 2X myosin isoform and shown that this myosin is coded by the MYH1 gene. More recently, we have revealed novel aspects of mitochondrial specialization in skeletal muscle fibers by single muscle fiber proteomics. Using the same approach we found that human fast and slow muscle fibers undergo strikingly different, in some case opposite, changes during aging, which are masked in whole muscle analyses.
We have developed a novel approach based on transfection of regenerating and adult skeletal muscle to explore the signaling pathways controlling the muscle phenotype, thus revealing the role of the calcineurin-NFAT pathway and the Akt-mTOR pathway in muscle fiber type and size, respectively. More recently, we have identified the MRF4-MEF2 axis as a major pathway regulating muscle hypertrophy. Finally, we have shown that the muscle phenotype undergoes major circadian changes that are in part controlled by the intrinsic muscle clock. In particular, the muscle clock regulated glucose uptake and oxidation, thus anticipating the metabolic changes associated with the transition from the rest/fasting phase to the active/feeding phase of the day/night cycle. Ongoing studies aim to determine how the intrinsic muscle clock affects lipid metabolism and the muscle response to adrenergic stimulation.
Professor Emeritus of General Pathology, University of Padova
- MD: University of Modena Medical School, Italy (1963)
- Professor of General Pathology, University of Padova (1965-2010)
- Director of the Consiglio Nazionale delle Ricerche (CNR) laboratory of Muscle Biology and Physiopathology, Padova (1987-2010)
- Visiting scientist, INSERM U127 (Hôpital Lariboisière) and Institut Pasteur, Paris (1986-87)
- 2017 – Honorary member, Associazione Biologia Cellulare & Differenziamento (ABCD)
- 2010 – Elected Member, Academia Europaea
- 1997 – Doctor honoris causa in Medicine, Paris 7 – Denis Diderot
- 1996 – Elected member, Accademia Nazionale dei Lincei
- 1988 – Doctor honoris causa in Medicine, University of Umeå