Lysosomes signal through the epigenome to regulate longevity across generations

IF 45.8 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Science Pub Date : 2025-09-25 DOI:10.1126/science.adn8754
Qinghao Zhang, Weiwei Dang, Meng C. Wang
{"title":"Lysosomes signal through the epigenome to regulate longevity across generations","authors":"Qinghao Zhang,&nbsp;Weiwei Dang,&nbsp;Meng C. Wang","doi":"10.1126/science.adn8754","DOIUrl":null,"url":null,"abstract":"<div >The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in <i>Caenorhabditis elegans</i>. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate–activated protein kinase (AMPK) or reduction of lysosomal mechanistic target of rapamycin (mTOR) signaling increased the expression of a histone H3.3 variant and increased its methylation on K79, leading to life-span extension across multiple generations. This transgenerational prolongevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase and was recapitulated by overexpressing H3.3 or the H3K79 methyltransferase. Thus, signals from a lysosome affect the epigenome and link the soma and germ line to mediate transgenerational inheritance of longevity.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"389 6767","pages":""},"PeriodicalIF":45.8000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.adn8754","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate–activated protein kinase (AMPK) or reduction of lysosomal mechanistic target of rapamycin (mTOR) signaling increased the expression of a histone H3.3 variant and increased its methylation on K79, leading to life-span extension across multiple generations. This transgenerational prolongevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase and was recapitulated by overexpressing H3.3 or the H3K79 methyltransferase. Thus, signals from a lysosome affect the epigenome and link the soma and germ line to mediate transgenerational inheritance of longevity.
溶酶体通过表观基因组发出信号来调节代际寿命
表观基因组对代谢输入敏感,对衰老至关重要。溶酶体作为信号中枢,感知代谢信号并调节寿命。我们发现,溶酶体代谢途径通过表观基因组信号调节秀丽隐杆线虫的跨代寿命。激活溶酶体脂质信号和溶酶体单磷酸腺苷活化蛋白激酶(AMPK)或减少溶酶体雷帕霉素机制靶蛋白(mTOR)信号可增加组蛋白H3.3变体的表达并增加其在K79上的甲基化,从而延长多代人的寿命。这种跨代延长寿命的作用需要组蛋白H3.3和种系特异性H3K79甲基转移酶从肠道到种系的转运,并通过过表达H3.3或H3K79甲基转移酶来重现。因此,来自溶酶体的信号影响表观基因组,连接体细胞和生殖系,介导长寿的跨代遗传。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Science
Science 综合性期刊-综合性期刊
CiteScore
61.10
自引率
0.90%
发文量
0
审稿时长
2.1 months
期刊介绍: Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信