Department of Neuroscience, Mayo Clinic, Jacksonville, United States.
Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Aichi, Japan.
Elife. 2020 Oct 19;9:e62199. doi: 10.7554/eLife.62199.
Although the ε2 allele of apolipoprotein E () benefits longevity, its mechanism is not understood. The protective effects of the 2 on Alzheimer's disease (AD) risk, particularly through their effects on amyloid or tau accumulation, may confound effects on longevity. Herein, we showed that the association between and longer lifespan persisted irrespective of AD status, including its neuropathology, by analyzing clinical datasets as well as animal models. Notably, was associated with preserved activity during aging, which also associated with lifespan. In animal models, distinct apoE isoform levels, where has the highest, were correlated with activity levels, while some forms of cholesterol and triglycerides were associated with apoE and activity levels. These results indicate that can contribute to longevity independent of AD. Preserved activity would be an early-observable feature of -mediated longevity, where higher levels of apoE2 and its-associated lipid metabolism might be involved.
尽管载脂蛋白 E () 的 ε2 等位基因有益于长寿，但它的机制尚不清楚。2 对阿尔茨海默病 (AD) 风险的保护作用，特别是通过对淀粉样蛋白或 tau 积累的影响，可能会混淆对长寿的影响。在此，我们通过分析临床数据集和动物模型表明，无论 AD 状态如何，包括其神经病理学，载脂蛋白 E 与更长的寿命之间的关联仍然存在。值得注意的是，在衰老过程中，载脂蛋白 E 与活动能力的保存有关，而活动能力也与寿命有关。在动物模型中，不同的载脂蛋白 E 同工型水平，其中载脂蛋白 E2 水平最高，与活动水平相关，而某些形式的胆固醇和甘油三酯与载脂蛋白 E 和活动水平相关。这些结果表明，载脂蛋白 E 可以独立于 AD 而促进长寿。活动能力的保存将是载脂蛋白 E 介导的长寿的一个早期可观察特征，其中较高水平的载脂蛋白 E2 及其相关的脂质代谢可能与之相关。
