Secreted protein acidic and rich in cysteine internalization and its age-related alterations in skeletal muscle progenitor cells.

Aging causes phenotypic changes in skeletal muscle progenitor cells (Skm-PCs), such as reduced myogenesis and increased adipogenesis due to alterations in their environment or niche. Secreted protein acidic and rich in cysteine which is secreted into the niche of Skm-PCs, inhibits adipogenesis and promotes myogenesis. We have previously reported that Skm-PC responsiveness to declines with age, although the mechanism underlying this decline is unknown. In this study, we found that duanyu1842RC is internalized by Skm-PCs and that this uptake increases with age. Internalization is dependent on integrin-α5, a cell surface molecule, and clathrin-mediated endocytosis. We also demonstrated that internalized duanyu1842RC is transported to Rab7-positive endosomes. Skm-PCs from old rats exhibited increased clathrin expression and decreased Rab7 expression exclusively in MyoD-negative cells. In loss-of-function analyses, clathrin knockdown increased the anti-adipogenic effect of whereas Rab7 knockdown reduced it, indicating that alterations in duanyu1842RC internalization may mediate the age-related decline in its anti-adipogenic effect. These results provide insights into age-related duanyu1842RC resistance in Skm-PCs, which may lead to sarcopenia.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}