Human and Animal Physiology, Wageningen University and Research, Wageningen, The Netherlands.
TI Food and Nutrition, Wageningen, The Netherlands.
J Cachexia Sarcopenia Muscle. 2021 Oct;12(5):1214-1231. doi: 10.1002/jcsm.12753. Epub 2021 Jul 4.
Due to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.
Eighteen older (69 ± 2.0 years) and 20 young (22 ± 2.0 years) males were recruited based on similar self-reported physical activity, which was verified using accelerometry measurements. Gene expression profiles of vastus lateralis biopsies obtained by RNA sequencing were compared, and key results were validated using quantitative polymerase chain reaction and western blot.
Total physical activity energy expenditure was similar between the young and old group (404 ± 215 vs. 411 ± 189 kcal/day, P = 0.11). Three thousand seven hundred ninety-seven differentially expressed coding genes (DEGs) were identified (adjusted P-value cut-off of <0.05), of which 1891 were higher and 1906 were lower expressed in the older muscle. The matrisome, innervation and inflammation were the main upregulated processes, and oxidative metabolism was the main downregulated process in old compared with young muscle. Lower protein levels of mitochondrial transcription factor A (TFAM, P = 0.030) and mitochondrial respiratory Complexes IV and II (P = 0.011 and P = 0.0009, respectively) were observed, whereas a trend was observed for Complex I (P = 0.062), in older compared with young muscle. Protein expression of Complexes I and IV was significantly correlated to mitochondrial capacity in the vastus lateralis as measured in vivo (P = 0.017, R = 0.42 and P = 0.030, R = 0.36). A trend for higher muscle-specific receptor kinase (MUSK) protein levels in the older group was observed (P = 0.08).
There are clear differences in the transcriptome signatures of the vastus lateralis muscle of healthy older and young males with similar physical activity levels, including significant differences at the protein level. By disentangling physical activity and ageing, we appoint early skeletal muscle ageing processes that occur despite similar physical activity. Improved understanding of these processes will be key to design targeted anti-ageing therapies.
由于骨骼肌肉衰老和生活方式因素之间的相互作用，往往难以将肌肉质量和功能的下降归因于生活方式的改变或年龄的增长本身。由于影响肌肉质量和功能的许多生理因素受身体活动调节，而身体活动随年龄增长而减少，因此本研究旨在通过比较一组具有相似身体活动模式的健康老年人和年轻人，更好地了解早期衰老对肌肉功能的影响。
根据相似的自我报告身体活动招募了 18 名老年人（69 ± 2.0 岁）和 20 名年轻人（22 ± 2.0 岁），这些活动通过加速度计测量得到了验证。通过 RNA 测序比较了取自股外侧肌的活检样本的基因表达谱，并使用定量聚合酶链反应和蛋白质印迹验证了关键结果。
年轻人和老年人的总体力活动能量消耗相似（404 ± 215 与 411 ± 189 kcal/天，P = 0.11）。鉴定出 3797 个差异表达的编码基因（调整后的 P 值 <0.05），其中 1891 个在老年人肌肉中表达上调，1906 个表达下调。与年轻人肌肉相比，基质、神经支配和炎症是上调的主要过程，氧化代谢是下调的主要过程。与年轻人肌肉相比，老年人肌肉中观察到线粒体转录因子 A（TFAM，P = 0.030）和线粒体呼吸复合物 IV 和 II（P = 0.011 和 P = 0.0009，分别）的蛋白水平较低，而复合物 I 则呈下降趋势（P = 0.062）。股外侧肌的复合物 I 和 IV 的蛋白表达与体内测量的线粒体容量呈显著相关（P = 0.017，R = 0.42 和 P = 0.030，R = 0.36）。在老年人组中，观察到肌肉特异性受体激酶（MUSK）蛋白水平有升高的趋势（P = 0.08）。
具有相似身体活动水平的健康老年男性和年轻男性的股外侧肌转录组特征存在明显差异，包括蛋白质水平的显著差异。通过分离身体活动和衰老，我们确定了尽管有相似的身体活动，但仍会发生早期骨骼肌肉衰老过程。更好地了解这些过程将是设计靶向抗衰老治疗的关键。
