Age-related decline in the expression of BRG1, ATM and ATR are partially reversed by dietary restriction in the livers of female mice.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Biogerontology Pub Date : 2024-11-01 Epub Date: 2024-07-06 DOI:10.1007/s10522-024-10117-7
Pynskhem Bok Swer, Babiangshisha Kharbuli, Donkupar Syiem, Ramesh Sharma
{"title":"Age-related decline in the expression of BRG1, ATM and ATR are partially reversed by dietary restriction in the livers of female mice.","authors":"Pynskhem Bok Swer, Babiangshisha Kharbuli, Donkupar Syiem, Ramesh Sharma","doi":"10.1007/s10522-024-10117-7","DOIUrl":null,"url":null,"abstract":"<p><p>BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1025-1037"},"PeriodicalIF":4.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-024-10117-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.

Abstract Image

在雌性小鼠肝脏中,与年龄相关的 BRG1、ATM 和 ATR 表达下降可通过限制饮食得到部分逆转。
BRG1(梵天相关基因 1)是 SWI/SNF(开关/蔗糖不发酵)染色质重塑复合体的成员,它利用 ATP 水解产生的能量进行活动。除了调节大量基因的表达外,BRG1 还能在基因毒性应激时介导 DNA 修复,并调节衰老。在机体衰老过程中,由于 DNA 修复机制逐渐崩溃,未修复/可修复的 DNA 损伤不断积累。本研究调查了 5 个月大和 21 个月大雌性小鼠肝脏中 BRG1 的表达水平与年龄的关系。研究还探讨了饮食限制对老龄(21 个月)小鼠 BRG1 表达的影响。研究的主要发现有实时 PCR 和 Western 印迹分析表明,5 个月大小鼠的 BRG1 水平较高,但随着年龄的增长会显著降低。饮食限制会增加 21 个月大小鼠的 BRG1 表达量,几乎恢复到较小鼠组的水平。随着年龄的增长,DNA损伤反应基因ATM(Ataxia Telangiectasia Mutated)和ATR(Ataxia Telangiectasia and Rad3-related)也出现了类似的表达模式,并且似乎受到饮食限制的调节。BRG1对ATM的转录调节与年龄和饮食限制有关。这些结果表明,随着小鼠年龄的增长,BRG1、ATM 和 ATR 的表达会降低,而饮食限制可以恢复它们的表达。这意味着饮食限制可能在调节BRG1及相关基因表达方面起着至关重要的作用,有可能随着小鼠年龄的增长而维持肝脏修复和代谢过程。
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
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
×
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:481959085
Book学术官方微信