Institute of Neuropathology, Justus-Liebig University, Giessen, Germany.
Leibnitz Institut für Analytische Wissenschaften-ISAS e.V., Dortmund, Germany.
Sci Rep. 2024 Oct 3;14(1):22965. doi: 10.1038/s41598-024-74913-4.
To gain a deeper understanding of skeletal muscle function in younger age and aging in elderly, identification of molecular signatures regulating these functions under physiological conditions is needed. Although molecular studies of healthy muscle have been conducted on adults and older subjects, there is a lack of research on infant muscle in terms of combined morphological, transcriptomic and proteomic profiles. To address this gap of knowledge, we performed RNA sequencing (RNA-seq), tandem mass spectrometry (LC-MS/MS), morphometric analysis and assays for mitochondrial maintenance in skeletal muscle biopsies from both, infants aged 4-28 months and adults aged 19-65 years. We identified differently expressed genes (DEGs) and differentially expressed proteins (DEPs) in adults compared to infants. The down-regulated genes in adults were associated with functional terms primarily related to sarcomeres, cellular maintenance, and metabolic, immunological and developmental processes. Thus, our study indicates age-related differences in the molecular signatures and associated functions of healthy skeletal muscle. Moreover, the findings assert that processes previously associated solely with aging are indeed part of development and healthy aging. Hence, combined findings of this study also indicate that age-dependent controls are crucial in muscle disease studies, as otherwise the comparative results may not be reliable.
为了更深入地了解年轻和老年时期的骨骼肌功能,需要确定在生理条件下调节这些功能的分子特征。虽然已经对成年人和老年人的健康肌肉进行了分子研究,但在形态、转录组和蛋白质组综合特征方面,婴儿肌肉的研究还很缺乏。为了弥补这一知识空白,我们对 4-28 个月大的婴儿和 19-65 岁的成年人的骨骼肌活检样本进行了 RNA 测序(RNA-seq)、串联质谱(LC-MS/MS)、形态计量分析和线粒体维持检测。我们在成年人与婴儿之间鉴定出了差异表达基因(DEGs)和差异表达蛋白(DEPs)。成年人中下调的基因与功能术语有关,主要与肌节、细胞维持以及代谢、免疫和发育过程有关。因此,我们的研究表明,健康骨骼肌的分子特征及其相关功能存在与年龄相关的差异。此外,这些发现表明,以前仅与衰老相关的过程实际上是发育和健康衰老的一部分。因此,本研究的综合发现还表明,在肌肉疾病研究中,年龄依赖性对照至关重要,否则比较结果可能不可靠。