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

Cells. 2023 Feb 22;12(5):691. doi: 10.3390/cells12050691.

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.

Keywords: ROS; SIRT3; mitochondria; molecular rehabilitation; muscle tissue; simulated microgravity; sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extraterrestrial Environment
  • Humans
  • Mars*
  • Muscles / metabolism
  • Sirtuin 3* / metabolism
  • Weightlessness*

Substances

  • Sirtuin 3
  • SIRT3 protein, human

Grants and funding

This work was supported by grant n. 2015-009-R.0, received from Italian Space Agency (ASI).