The precursor of PI(3,4,5)P-3 alleviates aging by activating daf-18(Pten) and independent of daf-16

doi:10.1038/s41467-020-18280-4

	The precursor of PI(3,4,5)P-3 alleviates aging by activating daf-18(Pten) and independent of daf-16
	Shi, Dawei 1,2,3; Xia, Xian 1,2,3; Cui, Aoyuan 3,4; Xiong, Zhongxiang1,5 ; Yan, Yizhen 1,3; Luo, Jing 1,6; Chen, Guoyu 1,3; Zeng, Yingying1,5 ; Cai, Donghong 1,3; Hou, Lei 1,3; McDermott, Joseph 1; Li, Yu 4; Zhang, Hong 3,7; Han, Jing-Dong J.1,2
	2020-09-08
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	11 期号:1 页码:#VALUE!
DOI	10.1038/s41467-020-18280-4
摘要	Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P-2 . MI and PI(4,5)P-2 are precursors of PI(3,4,5)P-3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000607106200001
出版者	NATURE RESEARCH
WOS关键词	EXTENDS LIFE-SPAN ; INSULIN SENSITIVITY ; C-ELEGANS ; INOSITOL ; MYOINOSITOL ; METABOLISM ; PATHWAYS ; GENE ; LONGEVITY ; EVOLUTION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125987
专题	生命科学与技术学院_硕士生
通讯作者	Han, Jing-Dong J.
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci SIBS,Key Lab Computat Biol, Collaborat Innovat Ctr Genet & Dev Biol,Max Planc, Ctr Excellence Mol Cell Sci,Shanghai Inst Nutr &, Shanghai 200031, Peoples R China; 2.Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Ctr Quantitat Biol CQB, Beijing 100871, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, SIBS, SINH, CAS Key Lab Nutr Metab & Food Safety, Shanghai 200031, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 6.Beijing Forestry Univ, Coll Biol Sci & Technol, Beijing, Peoples R China; 7.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China
推荐引用方式 GB/T 7714	Shi, Dawei,Xia, Xian,Cui, Aoyuan,et al. The precursor of PI(3,4,5)P-3 alleviates aging by activating daf-18(Pten) and independent of daf-16[J]. NATURE COMMUNICATIONS,2020,11(1):#VALUE!.
APA	Shi, Dawei.,Xia, Xian.,Cui, Aoyuan.,Xiong, Zhongxiang.,Yan, Yizhen.,...&Han, Jing-Dong J..(2020).The precursor of PI(3,4,5)P-3 alleviates aging by activating daf-18(Pten) and independent of daf-16.NATURE COMMUNICATIONS,11(1),#VALUE!.
MLA	Shi, Dawei,et al."The precursor of PI(3,4,5)P-3 alleviates aging by activating daf-18(Pten) and independent of daf-16".NATURE COMMUNICATIONS 11.1(2020):#VALUE!.