近日，美国宾夕法尼亚大学Nancy M. Bonini及其团队发现，衰老胶质细胞连接线粒体功能障碍和脂质积累。2024年6月5日，《自然》杂志在线发表了这项成果。

研究人员发现了衰老果蝇大脑中天然存在的衰老胶质细胞，并破译了它们的起源和影响。利用激活蛋白1（AP1）的活性来筛选衰老，研究人员确定衰老胶质细胞可在神经元线粒体功能障碍时出现。反过来，衰老胶质细胞又会促进非衰老胶质细胞的脂质积累；在培养中的衰老人类成纤维细胞中也能看到类似的效果。

靶向衰老胶质细胞中的AP1活性可减轻衰老生物标志物，延长果蝇的寿命和健康期，并防止脂质积累。然而，这些益处是以大脑氧化损伤的增加为代价的，神经元线粒体功能仍然很差。总之，这些研究结果描绘了体内自然发生的衰老胶质细胞的轨迹，并表明这些细胞与关键的衰老现象：线粒体功能障碍和脂质积累有关。

据介绍，衰老是一种细胞状态，与许多哺乳动物的衰老和老年性疾病有关。在急性期，衰老细胞可促进伤口愈合并防止肿瘤形成；但它们也会促发炎症，从而长期加剧组织衰退。虽然衰老细胞是抗衰老疗法的有效靶标，但这些细胞在体内形成的原因、它们如何影响组织衰老以及消除它们的效果仍不清楚。

附：英文原文

Title: Senescent glia link mitochondrial dysfunction and lipid accumulation

Author: Byrns, China N., Perlegos, Alexandra E., Miller, Karl N., Jin, Zhecheng, Carranza, Faith R., Manchandra, Palak, Beveridge, Connor H., Randolph, Caitlin E., Chaluvadi, V. Sai, Zhang, Shirley L., Srinivasan, Ananth R., Bennett, F. C., Sehgal, Amita, Adams, Peter D., Chopra, Gaurav, Bonini, Nancy M.

Issue&Volume: 2024-06-05

Abstract: Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species1,2. Acutely, senescent cells promote wound healing3,4 and prevent tumour formation5; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy6,7,8,9,10,11, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear12,13. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence14,15, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.

DOI: 10.1038/s41586-024-07516-8

Source: https://www.nature.com/articles/s41586-024-07516-8