Muscle specific aging signature of PDGFRα-positive stromal cells underlies the development of age-related sarcopenia
筋老化再生医学研究グループ 黒澤珠希 研究生
Skeletal muscle mass and function decline with age, which leads to the condition called sarcopenia. We have recently shown that PDGFRα+ stromal cells are required for homeostatic muscle maintenance and that age-related changes of those cells are involved in sarcopenia. However, the mechanism by which PDGFRα+ stromal cells maintain muscle health is not yet completely understood. PDGFRα+ stromal cells also exist in various organs other than muscle and they appear to play a specific role in each organ where they reside. In this study, we sought to understand the mechanism of sarcopenia by analyzing muscle specific aging feature of PDGFRα+ cells. We isolated PDGFRα+ cells from various organs of young and aged mice and examined their gene expression profiles by RNAseq. Through comparative analyses between young and aged cells, and among different organs, we revealed the aging signature of muscle PDGFRα+ cells. Among genes that define the aging signature, we focused on Keratocan (Kera). Expression of Kera was observed in muscle PDGFRα+ cells in a very specific manner and dramatically decreased as mice aged. Furthermore, Kera knockout mice showed decreased muscle mass and myofiber atrophy even at young stage. These results highlight the significance of aging signature of muscle PDGFRα+ cells in the development of sarcopenia.