Function of fibro-adipogenic progenitor cells in the context of skeletal muscle regeneration during aging: influence of the beta 2 adrenoceptor

• Grant number: 24/06725-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Elen Haruka Miyabara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/14909-5 - Influence of beta 2 adrenoceptor on the function of fibroadipogenic progenitor cells in the context of muscle regeneration in aged mice., BP.DR

Abstract

Skeletal muscle has an appreciable regenerative capacity, which is especially attributed to the action of muscle stem cells called satellite cells. Additionally, fibro-adipogenic progenitor cells (FAPs) resident in the skeletal muscle provide a favorable niche for satellite cells to act during muscle regeneration. However, during aging, FAPs act inefficiently after muscle injury, accumulating and aberrantly secreting profibrotic factors in skeletal muscles. Consequently, the activation and differentiation of satellite cells is compromised during muscle regeneration in the elderly. In this context, a better understanding of the cellular and molecular mechanisms that culminate in the reduced muscular regenerative response that occurs during aging is fundamental for the development of more efficient strategies to improve the muscular regenerative capacity and quality of life during aging, given that the life expectancy has grown significantly in the last recent decades. Thus, considering that 1) our research group previously reported that the absence of the beta 2 adrenoceptor in mice leads to abnormal remodeling of connective tissue in regenerating muscles and impairment of the muscle stem cell function, and consequently impaired structural and functional muscle regeneration, 2) a preliminary result from our laboratory suggests that the beta 2 adrenoceptor influences the gene expression of IL33, which is secreted by FAPs, during muscle regeneration in young mice,3) the beta 2 adrenoceptor contributes to the regulation of lipid and glucose metabolism during aging and beta 2 adrenergic stimulation promotes the repair of muscle injuries in aged mice subjected to chemical sympathectomy, as well as attenuates the reduction in the number of satellite cells and sympathetic activity ; and 4) FAPs critically influence satellite cell function and extracellular matrix repair during muscle regeneration and act aberrantly during aging, which contributes to deficient muscle regenerative capacity; it is possible to hypothesize that beta 2 adrenoceptor-dependent signaling influences the function of FAPs during muscle regeneration in the elderly. Therefore, the general objective of this project is to investigate the influence of beta 2 adrenoceptor on FAPs function in the context of muscle regeneration during aging. (AU)