Identification of potential therapeutic targets to improve stem cell function and muscle regeneration during aging.

• Grant number: 24/13447-8
• Support Opportunities: Research Projects - SPEC Program
• Start date: October 01, 2025
• End date: September 30, 2029
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Michael Kyba
• Grantee: Michael Kyba
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Elen Haruka Miyabara ; Rita de Cássia Ramos Perlingeiro

Abstract

The integrity of skeletal muscle mass and function is fundamental for the maintenance of quality of life. Adult skeletal muscles have a remarkable capacity of regeneration after injury mainly due to the presence of muscle stem cells, called satellite cells. In addition, the fibro-adipogenic progenitor cells (FAPs) assist satellite cells during the muscle regenerative process. However, during aging the function of satellite cells significantly decreases, which leads to a significant impairment of muscle regeneration. Considering that the life expectancy has progressively increased worldwide in the last decades, a better understanding of the cellular and molecular mechanisms involved in the deficit of the muscle regenerative potential, which occurs during aging, is essential for the development of more efficient strategies able to improve the regenerative potential of the aged skeletal muscle and consequently increase quality of life. In this context, our preliminary results suggest the potential of an eccentric exercise protocol to attenuate muscle environment culprits associated with aged muscles: inflammation and fibrosis. Therefore, the two main objectives of this project are i) to contribute to the better understanding of the age-related processes that contribute to the decline of the muscle regenerative capacity, and ii) to identify potential therapeutic targets modulated by the eccentric exercise in the muscle, to improve stem cell function and muscle regeneration during aging. Overall, our purpose is to analyze the potential of therapeutic targets, by manipulating their expression in satellite cells, FAPs and regenerating muscles from aged mouse models. Finally, we will also analyze the impact of these manipulations in the aged muscle niche on age-related processes of human skeletal muscle progenitor cells. (AU)