Influence of beta 2 adrenoceptor on the function of fibroadipogenic progenitor cells in the context of muscle regeneration in aged mice.

• Grant number: 24/14909-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2024
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Fernanda Vieira Botelho Delpupo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/06725-1 - Function of fibro-adipogenic progenitor cells in the context of skeletal muscle regeneration during aging: influence of the beta 2 adrenoceptor, AP.R

Abstract

Skeletal muscle is the most abundant organ in the body and has vast regenerative potential, attributed mainly to the protagonist muscle stem cells, called satellite cells. Fundamental in muscle growth, repair and regeneration, these cells are activated following muscle injury and are capable of recovering damaged myofibers. Furthermore, other cells, such as fibroadipogenic progenitor cells (FAPs), play an important role in muscle regeneration. Resident in skeletal muscle, FAPs provide a favorable niche for satellite cell activity and influence the repair of the extracellular matrix during muscle regeneration. It is known that aging causes a clonal selection of FAPs, stimulating their fibrogenic conversion over adipogenic, which induces greater deposition of extracellular matrix proteins and, consequently, greater fibrosis during the repair of muscle injuries. Furthermore, during aging, these cells act aberrantly and are unable to proliferate efficiently after muscle injury, modifying their ability to support the proliferation of satellite cells. In this context, understanding the cellular and molecular mechanisms that culminate in the reduced muscle regenerative response, such as the study of molecular regulators of the function of FAPs during muscle regeneration, resulting from aging, will be fundamental for the development of more efficient strategies for improving muscle regenerative capacity and quality of life in the elderly, given that the life expectancy of these individuals has grown significantly in recent decades. Thus, considering that the beta 2 adrenoceptor is a viable candidate for a molecular regulator, its absence in regenerating muscle impairs connective tissue remodeling, as well as delays the resolution of the inflammatory process and affects the function of satellite cells, our general objective will be to investigate the influence of beta 2 adrenoceptor on the function of FAPs in the context of muscle regeneration in elderly mice. This study could serve as a basis for the development of strategies aimed at improving regenerative capacity in the elderly.