Amazentis SA, EPFL Innovation Park, Batiment C, CH-1015, Lausanne, Switzerland.
Center for Human Drug Research, Zernikedreef 8, 2333 CL, Leiden, The Netherlands.
Sci Rep. 2018 Jun 4;8(1):8548. doi: 10.1038/s41598-018-26944-x.
Aging is accompanied by a gradual decline in both muscle mass and strength over time, which can eventually lead to pathologies, such as frailty and sarcopenia. While these two conditions are well characterized, further investigation of the early biological signs present in pre-frail elderly is still needed to help identify strategies for preventative therapeutic intervention. The goal of the present clinical study was to evaluate the level of mitochondrial (dys)function in a well-defined population of pre-frail elderly (>60 years of age). Pre-frail elderly were compared with an age-matched population of active elderly. Muscle mitochondrial function was assessed in vivo using phosphorus magnetic resonance spectroscopy (P-MRS) and a comprehensive set of biological biomarkers were measured ex vivo in vastus lateralis muscle biopsies. In pre-frail subjects, phosphocreatine recovery was impaired and mitochondrial respiratory complex protein and activity levels were significantly lower when compared with active elderly. Analysis of microarray data showed that mitochondrial genes were also significantly down-regulated in muscle of pre-frail compared to active elderly. These results show that mitochondrial impairment is a hallmark of pre-frailty development and the onset of decline in muscle function in the elderly.
随着时间的推移，衰老伴随着肌肉质量和力量的逐渐下降，这最终可能导致一些病理状态，如虚弱和肌肉减少症。虽然这两种情况已经得到了很好的描述，但仍需要进一步研究易发生衰弱的老年人中存在的早期生物学标志，以帮助确定预防治疗干预的策略。本临床研究的目的是评估明确界定的易发生衰弱的老年人（>60 岁）群体中线粒体（功能）障碍的水平。易发生衰弱的老年人与年龄匹配的活跃老年人进行了比较。使用磷磁共振波谱（P-MRS）在体内评估肌肉线粒体功能，并在股外侧肌活检中体外测量了一整套生物生物标志物。与活跃老年人相比，易发生衰弱的受试者的磷酸肌酸恢复受损，线粒体呼吸复合物蛋白和活性水平明显降低。微阵列数据分析表明，与活跃老年人相比，肌肉中线粒体基因也明显下调。这些结果表明，线粒体损伤是易发生衰弱发展和老年人肌肉功能下降的标志。
