Buck Institute的研究团队发现，罕见的长寿基因APOE2通过帮助脑细胞保护和修复DNA、抵抗细胞衰老来保护神经元[1]。这项发表在《Aging Cell》期刊上的研究表明，APOE2在减少DNA损伤和帮助神经元从压力中恢复方面优于其他两种常见形式APOE3和APOE4[1]。
研究人员在实验中发现，携带APOE2基因的神经元积累的DNA损伤显著少于携带其他基因变体的神经元[1]。当研究者向APOE4神经元添加重组APOE2蛋白时，这些细胞在放射线照射后显示DNA损伤信号降低[1]。这些发现为针对高阿尔茨海默病遗传风险人群开发新型治疗方法提供了可能[1]。
在动物模型中，年迈的APOE2敲入小鼠的核仁更小、核支架蛋白Lamin A/C水平更高，海马体的异染色质保存更好[1]。这些结果进一步证实了APOE2在防止细胞衰老中的关键作用。该研究由美国国立衰老研究所、Paul F. Glenn衰老生物学中心和Hevolution基金会等机构资助[1]。
Researchers at the Buck Institute for Research on Aging have discovered that the rare longevity gene APOE2 protects neurons by enabling brain cells to preserve and repair DNA while resisting cellular aging.[1] The findings, published in Aging Cell, reveal that APOE2 outperforms the more common APOE3 and APOE4 variants in reducing DNA damage and helping neurons recover from stress, potentially opening new therapeutic avenues for individuals at high genetic risk of Alzheimer's disease.[1]
The study identifies APOE4 as the strongest known genetic risk factor for late-onset Alzheimer's disease, which typically develops after age 65.[1] In contrast, neurons carrying APOE2 accumulated significantly less DNA damage than those with other gene variants.[1] When researchers added recombinant APOE2 protein to APOE4 neurons, the cells showed reduced DNA damage signals following radiation exposure.[1] Aged APOE2 knock-in mice displayed smaller nucleoli, elevated levels of the nuclear scaffolding protein Lamin A/C, and better preserved heterochromatin in the hippocampus—all markers associated with more youthful cellular aging profiles.[1] The research was supported by the National Institute on Aging, the Paul F. Glenn Center for Biology of Aging Research, and the Hevolution Foundation.[1]