Two conserved epigenetic regulators prevent healthy ageing

doi:10.1038/s41586-020-2037-y

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2037-y
	Two conserved epigenetic regulators prevent healthy ageing
	Yoshida, Kenichi 1; Gowers, Kate H. C.2; Lee-Six, Henry 1; Chandrasekharan, Deepak P.2; Coorens, Tim 1; Maughan, Elizabeth F.2; Beal, Kathryn 1; Menzies, Andrew 1; Millar, Fraser R.2; Anderson, Elizabeth 1; Clarke, Sarah E.2; Pennycuick, Adam 2; Thakrar, Ricky M.2,3; Butler, Colin R.2,3; Kakiuchi, Nobuyuki 4; Hirano, Tomonori 4; Hynds, Robert E.2,5; Stratton, Michael R.1; Martincorena, Inigo 1; Janes, Sam M.2,3; Campbell, Peter J.1,6
	2020-02-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
文章类型	Article;Early Access
语种	英语
国家	Peoples R China
英文关键词	It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated(1-6). Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan(4,7). 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 databases(8,9) 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. Two epigenetic regulators-identified in an RNA interference screen in Caenhorhabditis elegans, and conserved in mammals-diminish mitochondrial function and accelerate the age-related deterioration of behaviour.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000516702000006
WOS关键词	LIFE-SPAN ; MITOCHONDRIAL UPR ; LONGEVITY ; STRESS ; DOPAMINE ; PATHWAY ; MEMORY ; DNA
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281095
专题	地球科学资源环境科学气候变化
作者单位	1.Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England; 2.UCL, Lungs Living Res Ctr, UCL Resp, London, England; 3.Univ Coll London Hosp, Dept Thorac Med, London, England; 4.Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan; 5.UCL, UCL Canc Inst, CRUK Lung Canc Ctr Excellence, London, England; 6.Univ Cambridge, Stem Cell Inst, Cambridge, England
推荐引用方式 GB/T 7714	Yoshida, Kenichi,Gowers, Kate H. C.,Lee-Six, Henry,et al. Two conserved epigenetic regulators prevent healthy ageing[J]. NATURE,2020.
APA	Yoshida, Kenichi.,Gowers, Kate H. C..,Lee-Six, Henry.,Chandrasekharan, Deepak P..,Coorens, Tim.,...&Campbell, Peter J..(2020).Two conserved epigenetic regulators prevent healthy ageing.NATURE.
MLA	Yoshida, Kenichi,et al."Two conserved epigenetic regulators prevent healthy ageing".NATURE (2020).