2026-05-08 長寿医療研究センター研究所
図：骨格筋、視床下部、褐色脂肪組織の間の臓器間ネットワーク
＜関連情報＞
- https://www.ncgg.go.jp/ri/report/20260507.html
- https://www.sciencedirect.com/science/article/pii/S1550413126001415
筋肉由来のミメカンは、マウスの視床下部と褐色脂肪組織間のコミュニケーションを調節し、健康と寿命を促進する Muscle-derived Mimecan regulates hypothalamus-brown adipose tissue communication and promotes health and lifespan in mice
Kentaro Mori , Shin-ichiro Imai
Cell Metabolism Available online 7 May 2026
DOI:https://doi.org/10.1016/j.cmet.2026.04.003
Highlights
- Muscle-derived Mimecan regulates core body temperature via brown adipose tissue
- Mimecan activates MC4R-positive neurons in the DMH/DHA via maintaining primary cilia
- Restoring plasma Mimecan levels counteracts aging and promotes lifespan in aged mice
- Voluntary exercise improves core body temperature regulation via maintaining Mimecan
Summary
Inter-organ communication plays a critical role in mammalian aging and longevity control. Here, we identified Mimecan from transcriptomic comparisons between young and aged skeletal muscles. Skeletal muscle-derived Mimecan regulates core body temperature via brown adipose tissue (BAT), which is impaired in aged mice. Skeletal muscle-specific loss- and gain-of-function models demonstrate that Mimecan activates melanocortin 4 receptor (MC4R)-positive neurons in the dorsomedial hypothalamus (DMH) and dorsal hypothalamic area (DHA) via maintaining primary cilia in those neurons, enhancing the sympathetic nervous tone directed to BAT. Furthermore, DMH/DHA-specific Mc4r-knockdown completely abolishes the effect of Mimecan overexpression on BAT function. Lastly, the restoration of Mimecan levels in blood circulation significantly extends lifespan in aged mice, suggesting that Mimecan plays a critical role in counteracting aging and promoting lifespan. Taken together, this study demonstrates the importance of inter-organ communication between the hypothalamus, skeletal muscle, and BAT in the systemic regulation of mammalian aging and longevity.
