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量子位 报道 | 公众号 QbitAI

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哈佛医学院领衔的团队发现,活到85-100岁的人,比起只活到80 岁以内的人,这些基因的表达明显更少。



Harvard Gazette 还评价说:这项研究首次证明了神经系统真的会影响寿命。



在人类身上做的实验,用到了数百个捐赠的大脑,都是“在认知上没有缺陷 (Cognitively Intact) ”的大脑。也就是说,这些人去世之前,大脑还是健康的。

下图显示,70-80 岁85-101 岁两个组,大脑皮层的基因转录组,有明显不同的特征


红是基因表达水平提高,蓝是基因表达水平降低。85-101 岁,多是上蓝下红;70-80 岁,多是上红下蓝:


被抑制了的基因,有这些 (b-d 是三个部位的大脑皮层) ,它们都和神经活动有关:



科学家们联想到从前有研究提到:一种叫 REST 的转录因子,对防止神经过度兴奋可能有帮助。

是不是它抑制了大脑的过度神经活动 (从而延长寿命) ?

这件事在人类身上不容易得到证实,但 REST 这种蛋白质,是哺乳动物身上广泛存在的,所以团队先用小鼠做了实验。


REST 有缺陷的小鼠,比正常大鼠的大脑皮层活动更强,神经兴奋性也更高 (红 e) 。


小鼠寿命比较长,不便观察。而秀丽隐杆线虫身上,也有和 REST 同源的基因,spr-3spr-4

实验证明,当这些基因变异之后丧失了功能,长寿线虫变体 (daf-2) 的寿命就变短了:


不止是实验室培育的突变线虫,在野生线虫当中,spr-4 的过度表达抑制了兴奋,延长了寿命。



这项研究还揭示了神经兴奋和衰老之间联系,还指出了胰岛素 /IGF1 整合神经活动、以及代谢的途径。


此外,通过缓和神经兴奋的整体变化,在神经网络活动中保持适当的平衡,REST 还可以预防与年龄有关的神经系统疾病(比如老年痴呆),从而延长人类的寿命。

不过,先别忙着放空大脑,坐等活到 99。

论文的通讯作者 Yankner(扬克纳)严肃表示:











不过研究人员相信,进一步探明 REST 蛋白对长寿的作用,将推动相关靶向药物的研发,新的治疗手段值得期待。






科学家们不太可能开发出“REST 补充剂”之类的神奇药丸来延长人们的寿命,扬克纳说:












发帖时间: news

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