锻炼缓解内质网还原应激从而促进健康衰老  

Exercise Alleviates ER Reductive Stress and Promotes Healthy Aging

作　　者：王圆圆 乔新华[1] 时畅 叶傲君 郭苗苗 赵玉政[3] 陈畅[1,2] WANG Yuan-Yuan;QIAO Xin-Hua;SHI Chang;YE Ao-Jun;GUO Miao-Miao;ZHAO Yu-Zheng;CHEN Chang(National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]中国科学院生物物理研究所,生物大分子国家重点实验室,北京100101 [2]中国科学院大学,北京100049 [3]华东理工大学药学院,上海200237

出　　处：《生物化学与生物物理进展》2022年第3期444-453,共10页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(31900893,91849203);国家重点研发计划(2017YFA0504000);中国科学院先导计划(XDB39000000)资助项目。

摘　　要：目的锻炼是延缓衰老的有效策略,本工作的目的在于探索锻炼是如何在细胞器水平影响内质网的氧化还原状态,以及内质网氧化还原状态是否影响个体衰老。方法利用定位于内质网响应过氧化氢的Hyperion探针检测线虫衰老过程中及经过游泳运动后体壁肌肉内质网的氧化还原状态。通过在线虫内质网中特异过表达哺乳动物过氧化氢酶的同源基因ctl-1构建内质网特异的还原应激模型,研究了内质网还原应激对个体衰老的影响。线虫的健康状态以线虫寿命、身体摆动次数及对压力的响应能力为判断指标进行表征。结果用Hyperion;探针检测发现,衰老线虫的内质网中过氧化氢水平相比与年轻线虫显著降低,表明内质网在衰老过程中发生了还原应激。线虫经过短时90 min游泳运动及长时期4 d(3次+3次+2次+2次,90 min/次)的游泳运动都可以增加内质网的氧化力。相比于对照,内质网还原应激的线虫寿命缩短,身体摆动次数降低,应对压力的响应能力下降,表明内质网还原应激加速线虫衰老。进一步研究发现,长时期的锻炼可以提高内质网的氧化力,缓解衰老相关的内质网还原应激,经过锻炼的第8天的线虫运动活力显著高于未锻炼的第8天的线虫,而与第4天的线虫相似,表明锻炼延缓了线虫衰老。结论本工作揭示了锻炼对内质网氧化还原状态的调控,在个体水平发现内质网还原应激促进衰老,发现锻炼能增加内质网氧化力,改善衰老相关的内质网还原应激,促进健康衰老。本研究阐明了锻炼在细胞器水平对氧化还原的精准调控,从氧化还原角度揭示了锻炼促进健康衰老的新机制,提示维持内质网的氧化力是延缓衰老的潜在策略。Objective Exercise has been approved as an effective anti-aging approach.However,how exercise affects the organelle-specific redox status of the endoplasmic reticulum(ER)and whether it contributes to ER function and healthy aging are still unknown.Methods We constructed an ER-specific reductive stress C.elegans model that overexpresses ctl-1,a homolog of the mammalian catalase gene,to research the effect of ER reductive stress on aging at the organismal level.We then used the HyperionER probe which responds well to hydrogen peroxide to evaluate the redox status in the ER of body wall muscle during swimming and during aging.Results Our results show that H_(2)O_(2) in the ER was markedly reduced during aging and the number of body bending,the life span and the stress response ability in Pnfya-1::ctl-1_(ER)::mCherry C.elegans was markedly decreased compared with that in Pnfya-1::ctl-1-M_(ER)::mCherry,indicating that ER reductive stress occurs during the aging process and ER reductive stress promotes aging at the organismal level.Both short-term and long-term exercise can increase the oxidative power of the ER in C.elegans,and exercise alleviates the age-related ER reductive stress and promotes healthy aging.Conclusion Our results demonstrate the effect of exercise on ER redox status at the organelle level for the first time and uncover a new mechanism for exercise in delaying aging at the organismal level from the redox point of view,suggesting that maintaining the oxidation power of the ER may be a valuable geroprotective strategy.

关 键 词：锻炼 内质网 还原应激 衰老 线虫 应激反应 

分 类 号：Q26[生物学—细胞生物学]