Why sedentary life is detrimental while physical activity is so beneficial for healthy ageing? Which are the signalling pathways that control muscle mass/function and reverberate to whole body affecting disease onset and mortality?

According to World Health Organization, sedentary life is the fourth leading risks of global mortality while physical activity improves quality of life and survival (healthy ageing). In the last years my lab greatly contributes to identify the molecular details that regulate muscle mass and longevity pathways. We are interest in understanding the signaling pathways that control protein synthesis and degradation, organelle biogenesis, autophagy, transcriptional regulation and how these systems reverberate from muscles to whole body for a healthy ageing. To reach this goal we use a multidisciplinary approach including genetics, in vivo imaging, physiology, molecular biology and biochemistry at single cell as well as tissue level.

Skeletal muscles constitute the 40-50% of total body mass and play a critical role not only in locomotion and breathing but also in whole body metabolism. Skeletal muscles control glucose and lipid metabolism and are the major source of aminoacids during catabolic conditions such as cancer, cardiac failure, infections, burn injury and ageing. These acquired diseases as well as inherited muscle disorders are characterised by muscle wasting and weakness. People that face with muscle loss show an increased morbidity and mortality. Despite the aetiology, the pathogenetic mechanisms that induce muscle wasting are often shared by different diseases. The abnormal upregulation of protein breakdown systems, reduction of protein synthesis, impairment or drop of muscle stem cell and decreased regenerative capacity of muscle are believed to be responsible for muscle loss in ageing and many diseases. Importantly, a new concept is emerging from recent studies that consider the metabolic adaptations occurring in skeletal muscles as disease modifier/controller. For instance, changes in muscle metabolism override a mitochondrial problem in the heart and prevent the onset of dilated cardiomyopathy and heart failure.
Sandri group was the first to identify that protein breakdown requires a transcriptional-dependent program that regulates key and rate limiting enzymes of ubiquitin-proteasome and autophagy-lysosome systems. His lab also identified several unexpected links between pathways that control protein synthesis and muscle growth with the signalling of protein degradation. This knowledge was translated to several inherited muscle dystrophies and our lab was the first to identify autophagy impairment as a pathogenetic mechanism of muscle loss in Duchenne and Ullrich muscle dystrophies. Importantly, a nutritional-based clinical trial successfully showed that reactivation of autophagy is beneficial in patients. The connection between energy, mitochondria and nuclear programs that contrl the metabolic flexibility during exercise and how relevant is mitochondrial biogenesis and mitophagy are also topics in which Sandri lab greatly contributed in the last years. We now wish to understand how muscle programs that are under nutritional and physical activity/inactivity regulation systemically reverberate affecting distal organ function and life span.

MARCO SANDRI

  • MD: University of Padova, Italy (1996)
  • Specialist in Clinical Pathology: University of Padova (2001).
  • Postdoc: Department of Cell Biology, Harvard Medical School, Boston, USA (2002-2005).
  • Telethon Scientist, Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine (VIMM), Padova, Italy (2005-2015).
  • Assistant Professor: Department of Biomedical Science, Medical School, University of Padova, Padova, Italy (2006- 2013).
  • Associate Professor: Department of Biomedical Science, Medical School, University of Padova, Padova, Italy (2013- 2014).
  • Principal Investigator at Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy (2013-2015).
  • Adjunct Professor: Department of Medicine, Faculty of Medicine, McGill University, Montreal, Canada (since 2011).
  • Chair of the Myology Centre (CirMYO): University of Padova, Padova, Italy (2013-present).
  • Full Professor: Department of Biomedical Science, Medical School, University of Padova, Padova, Italy (since 2014)

Selected Awards

  • 2005-2010 – Telethon Career Award.
  • 2003 – “Terme Euganee Award” on Skeletal Muscle Regeneration, Reconstruction and Engineering.
  • 1997 – “Luigi Casati” prize, conferred by National Academy of Lincei.