Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-12-19 DOI:10.1126/science.adp6547

Wenwen Li, Jiarui Li, Jing Li, Chen Wei, Tal Laviv, Meiyi Dong, Jingran Lin, Mariah Calubag, Lesley A Colgan, Kai Jin, Bing Zhou, Ying Shen, Haohong Li, Yihui Cui, Zhihua Gao, Tao Li, Hailan Hu, Ryohei Yasuda, Huan Ma

{"title":"Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice","authors":"Wenwen Li, Jiarui Li, Jing Li, Chen Wei, Tal Laviv, Meiyi Dong, Jingran Lin, Mariah Calubag, Lesley A Colgan, Kai Jin, Bing Zhou, Ying Shen, Haohong Li, Yihui Cui, Zhihua Gao, Tao Li, Hailan Hu, Ryohei Yasuda, Huan Ma","doi":"10.1126/science.adp6547","DOIUrl":null,"url":null,"abstract":"Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TC mito ), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC nuc ). We demonstrated that E-TC mito repurposes molecules traditionally associated with E-TC nuc to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC mito weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC mito in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.","PeriodicalId":21678,"journal":{"name":"Science","volume":"42 1","pages":""},"PeriodicalIF":44.7000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1126/science.adp6547","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

Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TC mito ), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC nuc ). We demonstrated that E-TC mito repurposes molecules traditionally associated with E-TC nuc to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC mito weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC mito in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

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.