Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells

This study shows that matrix metalloproteinase-10 (MMP-10) is a key regulator of satellite cell integrity and skeletal muscle homeostasis during aging. Using MMP-10 knockout mice, the authors demonstrate that loss of MMP-10 in young animals induces premature aging–like changes in muscle, including extracellular matrix (ECM) remodeling, increased DNA damage, activation of senescence pathways (p16INK4a/pRb), and functional decline of satellite cells. MMP-10 deficiency disrupts the structure of the satellite cell niche, altering collagen IV, fibronectin, laminin, and β-dystroglycan organization, which promotes early exit from quiescence, reduced self-renewal, accelerated differentiation, and increased susceptibility to senescence under proliferative stress. Mechanistically, quiescent satellite cells express little Mmp10 mRNA, but MMP-10 protein is present in the niche and becomes transcriptionally induced in activated satellite cells, fibro-adipogenic progenitors, and myoblasts after injury. In vitro silencing of MMP-10 accelerates satellite cell senescence, whereas exogenous MMP-10 delays senescence and reduces DNA damage. In dystrophic mdx mice, systemic MMP-10 treatment reduces muscle damage and improves satellite cell integrity. Together, the results identify MMP-10 as a critical extrinsic and intrinsic factor that preserves satellite cell function and delays muscle stem cell aging, highlighting MMP-10 as a potential therapeutic target in sarcopenia and muscular dystrophy.