Gregory J. Tranah, Haley N. Barnes, Peggy M. Cawthon, Paul M. Coen, Karyn A. Esser, Russell T. Hepple, Zhiguang Huo, Philip A. Kramer, Frederico G. S. Toledo, Xiping Zhang, Kevin Wu, Christopher A. Wolff, Daniel S. Evans, Steven R. Cummings
{"title":"肌肉、活动能力和衰老研究》中,肌肉中线粒体氧化应激反应基因的表达与线粒体呼吸、体能和肌肉质量有关。","authors":"Gregory J. Tranah, Haley N. Barnes, Peggy M. Cawthon, Paul M. Coen, Karyn A. Esser, Russell T. Hepple, Zhiguang Huo, Philip A. Kramer, Frederico G. S. Toledo, Xiping Zhang, Kevin Wu, Christopher A. Wolff, Daniel S. Evans, Steven R. Cummings","doi":"10.1111/acel.14114","DOIUrl":null,"url":null,"abstract":"<p>Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO<sub>2</sub> peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins <i>SOD2</i>, <i>TRX2</i>, <i>PRX3</i>, <i>PRX5</i>, and <i>GRX2</i> were associated with higher levels of mitochondrial respiration and VO<sub>2</sub> peak. In addition, greater <i>SOD2, PRX3,</i> and <i>GRX2</i> expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8000,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14114","citationCount":"0","resultStr":"{\"title\":\"Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging\",\"authors\":\"Gregory J. Tranah, Haley N. Barnes, Peggy M. Cawthon, Paul M. Coen, Karyn A. Esser, Russell T. Hepple, Zhiguang Huo, Philip A. Kramer, Frederico G. S. Toledo, Xiping Zhang, Kevin Wu, Christopher A. Wolff, Daniel S. Evans, Steven R. Cummings\",\"doi\":\"10.1111/acel.14114\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO<sub>2</sub> peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins <i>SOD2</i>, <i>TRX2</i>, <i>PRX3</i>, <i>PRX5</i>, and <i>GRX2</i> were associated with higher levels of mitochondrial respiration and VO<sub>2</sub> peak. In addition, greater <i>SOD2, PRX3,</i> and <i>GRX2</i> expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.</p>\",\"PeriodicalId\":55543,\"journal\":{\"name\":\"Aging Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2024-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14114\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/acel.14114\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acel.14114","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging
Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO2 peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins SOD2, TRX2, PRX3, PRX5, and GRX2 were associated with higher levels of mitochondrial respiration and VO2 peak. In addition, greater SOD2, PRX3, and GRX2 expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.
期刊介绍:
Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.