M2 macrophage-derived TGF-β induces age-associated loss of adipogenesis through progenitor cell senescence

• DOI: 10.1016/j.molmet.2024.101943
• Publication Date: 2024-04-23T01:46:45Z
• Authors: Xinyi Zeng; Teh-Wei Wang; Kiyoshi Yamaguchi; Seira Hatakeyama; Satoshi Yamazaki; Eigo Shimizu; Seiya Imoto; Yoichi Furukawa; Yoshikazu Johmura; Makoto Nakanishi
• Keywords: Senescence; Adipose tissue macrophages

Adipose tissue is an endocrine and energy storage organ composed of several different cell types, including mature adipocytes, stromal cells, endothelial a variety immune cells. aging contributes to the pathogenesis metabolic dysfunction likely induced by crosstalk between adipose progenitor cells (APCs) but underlying molecular mechanisms remain largely unknown. In this study, we revealed biological role p16high senescent APCs, investigated each type in aged white tissue. We performed single-cell RNA sequencing (scRNA-seq) analysis on sorted from p16-CreERT2/Rosa26-LSL-tdTomato mice. also time serial age-dependent bulk RNA-seq datasets human mouse tissues infer transcriptome alteration adipogenic potential within aging. show that M2 macrophage-derived TGF-β induces APCs senescence which impairs adipogenesis vivo. increase with age loss potential. The ligand-receptor interaction reveals macrophages are donors for recipients. Indeed, treatment TGF-β1 phenotypes through mitochondrial ROS-mediated DNA damage vitro. injection into gonadal (gWAT) suppresses fibrotic genes as well p16 APCs. A gWAT atrophy observed cancer cachexia senescence, whose induction appeared be independent induction. Our results suggest age-related lipodystrophy senescence. damage, ROS, finally cellular