Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay; Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Cell Rep. 2023 Oct 31;42(10):113269. doi: 10.1016/j.celrep.2023.113269.
Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.
新出现的证据表明，免疫受体可能参与许多与衰老相关的过程，如能量代谢、炎症和认知能力下降。CD300f 是一种类似 Trem2 的脂质感应免疫受体，是一种特殊的受体，因为它整合了激活和抑制细胞信号通路，调节炎症、细胞凋亡和小胶质细胞代谢适应性。我们假设 CD300f 可以调节与衰老相关的全身过程，并最终延长健康寿命。我们密切关注了两种品系的 CD300f 和 WT 雌雄小鼠的几个队列 30 个月，发现敲除小鼠的寿命和健康寿命有重要缩短。这与全身炎症老化、认知能力下降增加、FDG PET 扫描观察到的大脑葡萄糖摄取减少、小胶质细胞衰老/神经退行性变表型富集、蛋白质稳态改变、衰老、脆弱性增加以及性别依赖性全身代谢变化有关。此外，CD300f 的缺失改变了巨噬细胞的免疫代谢表型。总之，我们提供了强有力的证据表明髓样细胞 CD300f 免疫受体有助于健康衰老。
