Strategy to improve the function of satellite cells and fibro-adipogenic progenitors (FAPs) of regenerating skeletal muscle during aging: implications of the modulation of S100A8 expression

• Grant number: 23/10309-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Elen Haruka Miyabara
• Grantee: Audrei dos Reis Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 25/05922-0 - Effect of S100A8 knockdown in the regeneration of human iPSC-derived myogenic progenitor in dystrophic skeletal muscle., BE.EP.PD

Abstract

Skeletal muscle has a great ability to regenerate after injuries due to the action of muscle stem cells called satellite cells. Furthermore, after muscle damage, fibro-adipogenic progenitor cells (FAPs) resident in skeletal muscle are activated, proliferate and provide a favorable environment for the occurrence of muscle regeneration mediated by satellite cells. However, during aging, FAPs do not act efficiently after muscle injury, impairing their ability to support the action of satellite cells during muscle regeneration. In addition, elderly individuals have impaired function of satellite cells and FAPs, the latter of which are accumulated and contribute to the aberrant production of profibrotic factors in skeletal muscle. Consequently, there is impairment in the niche of activation and differentiation of satellite cells during muscle regeneration in the elderly. In this context, strategies capable of improving the function of satellite cells and FAPs and consequently the regenerative capacity of the skeletal muscles of the elderly remain under constant investigation and are extremely important for improving the quality of life of these individuals, whose life expectancy has increased significantly. Considering that: a) preliminary results from our research group demonstrated a robust increase in the gene expression of S100A8 in regenerating muscle of elderly mice; b) a significant reduction of this gene was observed in muscle from animal model of Marfan syndrome submitted to low-intensity eccentric training, accompanied by attenuation of important deleterious muscular effects of this syndrome; such as a reduction in the number of positive CD11b macrophages (secretors of S100A8), decrease in the number of muscle fibers with a rounded shape, as well as in the expression of the extracellular matrix protein fibronectin; and c) the deleterious effects of aging and Marfan syndrome on skeletal muscle have similarities, such as changes in the number of inflammatory cells as well as an increase in the content of extracellular matrix proteins; it is possible to hypothesize that the modulation of S100A8 expression in injured skeletal muscle of old animals is a strategy capable of improving the function of satellite cells and FAPs in order to reduce the inflammatory process and enhance muscle regeneration during aging.