Abstract
Muscle inflammation, fibrosis
FAP, MUSCLE INFLAMMATION, INFLAMMATION, FIBROSIS, COMPLICATIONS
Muscle inflammation and fibrosis underlie disuse‐related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling and poor muscle recovery after disuse. In rodents, metformin has been shown to prevent cellular senescence/senescent associated secretory phenotype (SASP), inflammation, and fibrosis making it a potentially practical therapeutic solution. Thus, the purpose of this study was to determine in older adults if metformin monotherapy during bed rest could reduce muscle fibrosis and cellular senescence/SASP during the re‐ambulation period. A two‐arm controlled trial was utilized in healthy male and female older adults (Metformin was provided to older adults 2 weeks prior and during 5‐days of bed rest and was withdrawn during re‐ambulation. Re‐ambulation after acute disuse in older adults treated with metformin resulted in decreased markers of cellular senescence and senescence associated secretory phenotype (SASP), a decrease in muscle fibro‐adipogenic progenitor (FAP) myofibroblast populations, and lower muscle fibrosis.
Jonathan J. Petrocelli and Alec I. McKenzie contributed equally.This study is registered on 