Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions

doi:10.1038/s41467-023-39118-9

	Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions
	Fan, Shengjie 1; Yan, Yingxuan 1; Xia, Ying 2,3; Zhou, Zhenyu 1; Luo, Lingling 1; Zhu, Mengnan4,5,6,7 ; Han, Yongli 1; Yao, Deqiang8 ; Zhang, Lijun 1; Fang, Minglv 1; Peng, Lina4,5,6,7 ; Yu, Jing 1; Liu, Ying 1; Gao, Xiaoyan 1; Guan, Huida 9; Li, Hongli 1; Wang, Changhong 9; Wu, Xiaojun 9; Zhu, Huanhu4 ; Cao, Yu 2,3; Huang, Cheng 1
	2023-06-08
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	14 期号:1
发表状态	已发表
DOI	10.1038/s41467-023-39118-9
摘要	Citrus fruit has long been considered a healthy food, but its role and detailed mechanism in lifespan extension are not clear. Here, by using the nematode C. elegans, we identified that nomilin, a bitter-taste limoloid that is enriched in citrus, significantly extended the animals' lifespan, healthspan, and toxin resistance. Further analyses indicate that this ageing inhibiting activity depended on the insulin-like pathway DAF-2/DAF-16 and nuclear hormone receptors NHR-8/DAF-12. Moreover, the human pregnane X receptor (hPXR) was identified as the mammalian counterpart of NHR-8/DAF-12 and X-ray crystallography showed that nomilin directly binds with hPXR. The hPXR mutations that prevented nomilin binding blocked the activity of nomilin both in mammalian cells and in C. elegans. Finally, dietary nomilin supplementation improved healthspan and lifespan in D-galactose- and doxorubicin-induced senescent mice as well as in male senescence accelerated mice prone 8 (SAMP8) mice, and induced a longevity gene signature similar to that of most longevity interventions in the liver of bile-duct-ligation male mice. Taken together, we identified that nomilin may extend lifespan and healthspan in animals via the activation of PXR mediated detoxification functions.
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收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China["82073951","32170837"] ; Science and Technology Commission of Shanghai Municipality["20S11902000","16PJ1407400"] ; National Key R&D Program of China["2019YFA0802804","2021YFA0804701"] ; Fok Ying Tung Education Foundation[171036]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001047512000033
出版者	NATURE PORTFOLIO
引用统计	被引频次：24[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/325779
专题	生命科学与技术学院生命科学与技术学院_PI研究组_朱焕乎组 iHuman研究所 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站生命科学与技术学院_博士生
通讯作者	Zhu, Huanhu; Cao, Yu; Huang, Cheng
作者单位	1.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med,Dept Orthopaed, Shanghai Key Lab Orthopaed Implant, Shanghai 200011, Peoples R China 3.Shanghai Jiao Tong Univ, Peoples Hosp 9, Inst Precis Med, Sch Med, 115 Jinzun Rd, Shanghai 200125, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.ShanghaiTech Univ, IHuman Inst, Shanghai 201210, Peoples R China 9.Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai 201203, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Fan, Shengjie,Yan, Yingxuan,Xia, Ying,et al. Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions[J]. NATURE COMMUNICATIONS,2023,14(1).
APA	Fan, Shengjie.,Yan, Yingxuan.,Xia, Ying.,Zhou, Zhenyu.,Luo, Lingling.,...&Huang, Cheng.(2023).Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions.NATURE COMMUNICATIONS,14(1).
MLA	Fan, Shengjie,et al."Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions".NATURE COMMUNICATIONS 14.1(2023).