Nature neurosci—逆转脑衰老，需要靶向3种脑内细胞！！

中文摘要

神经系统老化的一个标志是脑白质体积和功能的下降，但导致白质病变的潜在机制尚不清楚。在目前的研究中，研究人员发现衰老小鼠白质中与年龄相关的少突胶质细胞状态的改变以及总少突胶质密度的降低。通过单细胞RNA测序，研究人员鉴定了干扰素（IFN）反应性少突胶质细胞，这些细胞位于衰老白质中CD8+T细胞附近。功能性淋巴细胞的缺失减少了IFN反应性少突胶质细胞的数量，挽救了少突胶质的丢失，而T细胞检查点抑制使衰老反应恶化。此外，他们在衰老白质中CD8+T细胞附近发现了淋巴细胞依赖性、IFN反应性小胶质细胞亚群。总之，研究人员提供证据表明CD8+T细胞诱导的、IFN应答的少突胶质细胞和小胶质细胞是白质老化的重要调节因子。

英文摘要

A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8+ T cells in aging white matter. Absence of functional lymphocytes decreased the number of IFN-responsive oligodendrocytes and rescued oligodendrocyte loss, whereas T-cell checkpoint inhibition worsened the aging response. In addition, we identified a subpopulation of lymphocyte-dependent, IFN-responsive microglia in the vicinity of the CD8+ T cells in aging white matter. In summary, we provide evidence that CD8+ T-cell-induced, IFN-responsive oligodendrocytes and microglia are important modifiers of white matter aging.

参考文献：CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging. Nat Neurosci. 2022 Oct 24. doi: 10.1038/s41593-022-01183-6. Online ahead of print.

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