中國科學家揭示阻礙健康衰老的保守調節因子
作者：
小柯機器人發布時間：2020/2/27 10:50:13
中國科學院神經科學研究所蔡時青和上海巴斯德研究所江陸斌研究團隊合作取得一項新突破。他們發現了兩個保守的表觀遺傳調控因子阻止健康衰老。相關論文於2020年2月26日在線發表在《自然》雜誌上。
研究人員揭示了健康老齡化的保守表觀遺傳機制。通過基於全基因組的RNA幹擾，研究人員對調節老年秀麗隱杆線蟲行為退化的基因進行了篩選，並確定了59個基因作為年齡相關行為退化率的潛在調節因子。在這些調節因子中，研究人員發現神經元表觀遺傳閱讀器BAZ-2和神經元組蛋白3賴氨酸9甲基轉移酶SET-6通過破壞線粒體功能、抑制核編碼線粒體蛋白的表達來加速線蟲行為退化。該機制在培養的小鼠神經元和人類細胞中都是保守的。對人類資料庫的檢索表明，這些秀麗隱杆線蟲調節因子BAZ2B和EHMT1的人類直系同源物在額葉皮層中的表達隨年齡增長而增加，並且與阿爾茨海默氏病的進展呈正相關。
此外，小鼠中Baz-2直系同源物Baz2b的缺失可減弱年齡相關的體重增加，並阻止衰老小鼠認知能力的下降。因此，在秀麗隱杆線蟲中的全基因組RNA幹擾篩選揭示了與衰老相關的保守表觀遺傳負調控因子，並暗示了實現健康衰老的可能方法。
據介紹，長期以來，人們一直認為壽命和健康壽命之間存在很強的相關性，但是可以清楚地將兩者分開。儘管總體來說人們的預期壽命有所增加，但壽命的延長很少伴隨著健康期的延長。因此，了解老年人健康行為的起源仍然是一項重要且具有挑戰性的任務。
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