Skeletal muscle mitochondrial DNA copy number and mitochondrial DNA deletion mutation frequency as predictors of physical performance in older men and women
Skeletal muscle mitochondrial DNA copy number and mitochondrial DNA deletion mutation frequency as predictors of physical performance in older men and women
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骨骼肌线粒体 DNA 拷贝数和线粒体 DNA 缺失突变频率作为老年男性和女性身体表现的预测因子
DOI：
10.1007/s11357-021-00351-z
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发表时间：
2021-03-19
期刊：
影响因子：
5.6
通讯作者：
Wanagat, Jonathan
中科院分区：
文献类型：
--
作者：
Herbst, Allen;Prior, Steven J.;Wanagat, Jonathan
线粒体DNA(MtDNA)的质量和数量与衰老的两个特征--基因组不稳定和线粒体功能障碍有关。体能表现依赖于线粒体的完整性，并随着年龄的增长而下降，然而mtDNA数量、质量和体能表现之间的相互作用尚不清楚。使用一种有效的针对mtDNA缺失的数字PCR方法，我们检验了骨骼肌mtDNA缺失突变频率(即mtDNA质量的衡量标准)或mtDNA拷贝数预测老年人体能表现的假设。从股外侧肌活检组织中提取总DNA，用数字聚合酶链式反应检测线粒体DNA拷贝数和缺失频率。这些活检来自53名年龄在50岁到86岁之间的成年人的横断面队列。在活检术前，收集体能指标，包括最大摄氧量、改良体能测试分数、6分钟步行距离、步速、握力、总倾斜和腿部质量。使用线性回归模型评估年龄、性别和结果之间的关系。我们发现线粒体DNA缺失突变频率随着年龄的增长呈指数增加。平均而言，从50岁到86岁，缺失频率从0.008增加到0.15%，增加了18倍。在年龄较大的时候，女性的缺失频率可能比男性低。我们还测量了男女的VO2max和mtDNA拷贝数随年龄的下降。从单个骨骼肌活检中测量的mtDNA缺失频率可以预测13.3%的VO2max变异。拷贝数解释了线粒体DNA缺失频率变异的22.6%，解释了瘦肉质量变异的10.4%。我们发现了年龄、mtDNA缺失突变频率、mtDNA拷贝数和体能之间的预测关系。这些数据与线粒体功能和基因组完整性在维持随年龄增长的体能表现方面的作用是一致的。在更大的队列和纵向研究中对线粒体DNA的质量和数量进行分析，可以扩大我们对线粒体DNA在人类衰老和长寿中的重要性的理解。
Mitochondrial DNA (mtDNA) quality and quantity relate to two hallmarks of aging-genomic instability and mitochondrial dysfunction. Physical performance relies on mitochondrial integrity and declines with age, yet the interactions between mtDNA quantity, quality, and physical performance are unclear. Using a validated digital PCR assay specific for mtDNA deletions, we tested the hypothesis that skeletal muscle mtDNA deletion mutation frequency (i.e., a measure of mtDNA quality) or mtDNA copy number predicts physical performance in older adults. Total DNA was isolated from vastus lateralis muscle biopsies and used to quantitate mtDNA copy number and mtDNA deletion frequency by digital PCR. The biopsies were obtained from a cross-sectional cohort of 53 adults aged 50 to 86 years. Before the biopsy procedure, physical performance measurements were collected, including VO2max, modified physical performance test score, 6-min walk distance, gait speed, grip strength, and total lean and leg mass. Linear regression models were used to evaluate the relationships between age, sex, and the outcomes. We found that mtDNA deletion mutation frequency increased exponentially with advancing age. On average from ages 50 to 86, deletion frequency increased from 0.008 to 0.15%, an 18-fold increase. Females may have lower deletion frequencies than males at older ages. We also measured declines in VO2max and mtDNA copy number with age in both sexes. The mtDNA deletion frequency measured from single skeletal muscle biopsies predicted 13.3% of the variation in VO2max. Copy number explained 22.6% of the variation in mtDNA deletion frequency and 10.4% of the lean mass variation. We found predictive relationships between age, mtDNA deletion mutation frequency, mtDNA copy number, and physical performance. These data are consistent with a role for mitochondrial function and genome integrity in maintaining physical performance with age. Analyses of mtDNA quality and quantity in larger cohorts and longitudinal studies could extend our understanding of the importance of mitochondrial DNA in human aging and longevity.