Role of SIRT3 in Microgravity Response: A New Player in Muscle Tissue Recovery

Author:

Aventaggiato Michele1ORCID,Barreca Federica1,Vitiello Laura2ORCID,Vespa Simone3ORCID,Valente Sergio4ORCID,Rotili Dante4ORCID,Mai Antonello4ORCID,Lotti Lavinia Vittoria1ORCID,Sansone Luigi56ORCID,Russo Matteo A.56ORCID,Bizzarri Mariano1ORCID,Ferretti Elisabetta1ORCID,Tafani Marco1ORCID

Affiliation:

1. Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy

2. Laboratory of Flow Cytometry, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy

3. Center for Advanced Studies and Technology, University “G. d’Annunzio” of Chieti-Pescara, Via Luigi Polacchi 11, 66100 Chieti, Italy

4. Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, Italy

5. MEBIC Consortium, San Raffaele University, 00166 Rome, Italy

6. Cellular and Molecular Pathology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy

Abstract

Life on Earth has evolved in the presence of a gravity constraint. Any change in the value of such a constraint has important physiological effects. Gravity reduction (microgravity) alters the performance of muscle, bone and, immune systems among others. Therefore, countermeasures to limit such deleterious effects of microgravity are needed considering future Lunar and Martian missions. Our study aims to demonstrate that the activation of mitochondrial Sirtuin 3 (SIRT3) can be exploited to reduce muscle damage and to maintain muscle differentiation following microgravity exposure. To this effect, we used a RCCS machine to simulate microgravity on ground on a muscle and cardiac cell line. During microgravity, cells were treated with a newly synthesized SIRT3 activator, called MC2791 and vitality, differentiation, ROS and, autophagy/mitophagy were measured. Our results indicate that SIRT3 activation reduces microgravity-induced cell death while maintaining the expression of muscle cell differentiation markers. In conclusion, our study demonstrates that SIRT3 activation could represent a targeted molecular strategy to reduce muscle tissue damage caused by microgravity.

Funder

Italian Space Agency

Publisher

MDPI AG

Subject

General Medicine

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