National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Clinical Research Core, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Int J Mol Sci. 2020 Dec 15;21(24):9540. doi: 10.3390/ijms21249540.
Although mitochondrial dysfunction has been implicated in aging, physical function decline, and several age-related diseases, an accessible and affordable measure of mitochondrial health is still lacking. In this study we identified the proteomic signature of muscular mitochondrial oxidative capacity in plasma. In 165 adults, we analyzed the association between concentrations of plasma proteins, measured using the SOMAscan assay, and skeletal muscle maximal oxidative phosphorylation capacity assessed as post-exercise phosphocreatine recovery time constant (τ) by phosphorous magnetic resonance spectroscopy. Out of 1301 proteins analyzed, we identified 87 proteins significantly associated with τ, adjusting for age, sex, and phosphocreatine depletion. Sixty proteins were positively correlated with better oxidative capacity, while 27 proteins were correlated with poorer capacity. Specific clusters of plasma proteins were enriched in the following pathways: homeostasis of energy metabolism, proteostasis, response to oxidative stress, and inflammation. The generalizability of these findings would benefit from replication in an independent cohort and in longitudinal analyses.
虽然线粒体功能障碍与衰老、身体功能下降和几种与年龄相关的疾病有关，但仍然缺乏一种易于获得和负担得起的线粒体健康衡量标准。在这项研究中，我们确定了肌肉线粒体氧化能力在血浆中的蛋白质组学特征。在 165 名成年人中，我们分析了使用 SOMAscan 测定法测量的血浆蛋白浓度与通过磷磁共振光谱法评估的运动后磷酸肌酸恢复时间常数（τ）之间的关联。在分析的 1301 种蛋白质中，我们确定了 87 种与 τ 显著相关的蛋白质，这些蛋白质经过年龄、性别和磷酸肌酸耗竭的调整。60 种蛋白质与更好的氧化能力呈正相关，而 27 种蛋白质与较差的氧化能力相关。血浆蛋白的特定簇在以下途径中富集：能量代谢的动态平衡、蛋白质稳态、对氧化应激的反应和炎症。这些发现的普遍性将受益于在独立队列和纵向分析中的复制。
