小柯机器人

中国科学院神经科学研究所蔡时青和上海巴斯德研究所江陆斌研究团队合作取得一项新突破。他们发现了两个保守的表观遗传调控因子阻止健康衰老。相关论文于2020年2月26日在线发表在《自然》杂志上。

研究人员揭示了健康老龄化的保守表观遗传机制。通过基于全基因组的RNA干扰，研究人员对调节老年秀丽隐杆线虫行为退化的基因进行了筛选，并确定了59个基因作为年龄相关行为退化率的潜在调节因子。在这些调节因子中，研究人员发现神经元表观遗传阅读器BAZ-2和神经元组蛋白3赖氨酸9甲基转移酶SET-6通过破坏线粒体功能、抑制核编码线粒体蛋白的表达来加速线虫行为退化。该机制在培养的小鼠神经元和人类细胞中都是保守的。对人类数据库的检索表明，这些秀丽隐杆线虫调节因子BAZ2B和EHMT1的人类直系同源物在额叶皮层中的表达随年龄增长而增加，并且与阿尔茨海默氏病的进展呈正相关。

此外，小鼠中Baz-2直系同源物Baz2b的缺失可减弱年龄相关的体重增加，并阻止衰老小鼠认知能力的下降。因此，在秀丽隐杆线虫中的全基因组RNA干扰筛选揭示了与衰老相关的保守表观遗传负调控因子，并暗示了实现健康衰老的可能方法。

据介绍，长期以来，人们一直认为寿命和健康寿命之间存在很强的相关性，但是可以清楚地将两者分开。尽管总体来说人们的预期寿命有所增加，但寿命的延长很少伴随着健康期的延长。因此，了解老年人健康行为的起源仍然是一项重要且具有挑战性的任务。

附：英文原文

Title: Two conserved epigenetic regulators prevent healthy ageing

Author: Jie Yuan, Si-Yuan Chang, Shi-Gang Yin, Zhi-Yang Liu, Xiu Cheng, Xi-Juan Liu, Qiang Jiang, Ge Gao, De-Ying Lin, Xin-Lei Kang, Shi-Wei Ye, Zheng Chen, Jiang-An Yin, Pei Hao, Lubin Jiang, Shi-Qing Cai

Issue&Volume: 2020-02-26

Abstract: It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated1,2,3,4,5,6. Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan4,7. Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases8,9 shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer’s disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing.

DOI: 10.1038/s41586-020-2037-y

Source: https://www.nature.com/articles/s41586-020-2037-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html