Tranah Gregory J, Barnes Haley N, Cawthon Peggy M, Coen Paul M, Esser Karyn A, Hepple Russell T, Huo Zhiguang, Kramer Philip A, Toledo Frederico G S, Evans Daniel S, Cummings Steven R
California Pacific Medical Center Research Institute, San Francisco, California, USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
medRxiv. 2023 Nov 6:2023.11.05.23298108. doi: 10.1101/2023.11.05.23298108.
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 twenty-one 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 peak, 400m 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 , , , , and were associated with higher levels of mitochondrial respiration and VO peak. In addition, greater and 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.
老年个体骨骼肌中的基因表达可能反映了对氧化损伤的代偿性适应，这种适应可维持组织完整性并保持功能。确定老年个体氧化应激反应基因表达模式与线粒体功能、身体机能及肌肉质量之间的关联，将增进我们对与管理分子损伤相关机制的了解，而这些机制可能是维持身体恢复力的靶点。为了表征负责氧化应激反应的基因的表达模式，从肌肉、 Mobility和衰老研究中收集的575名参与者（≥70岁）的骨骼肌活检样本中提取RNA并进行测序。分析了与氧化应激反应相关的21种蛋白质编码RNA的表达水平与六种表型指标的关系，这些指标包括：肌肉活检样本中的最大线粒体呼吸（最大氧化磷酸化）、身体机能（VO峰值、400米步行速度和腿部力量）以及肌肉大小（大腿肌肉体积和全身D3Cr肌肉质量）。在各结果中最一致相关的氧化应激反应基因的mRNA水平优先在线粒体内表达。编码通常位于线粒体的蛋白质的mRNA（、、、、和）的较高表达与较高水平的线粒体呼吸和VO峰值相关。此外，较高的和表达与较高的身体机能和肌肉大小相关。确定与多个机能和身体领域的高功能相关的特定机制，可能会带来针对性更强的抗氧化干预措施，对活动能力和独立性产生更大影响。
