Microarray profiling of gene expression in ageing murine skeletal muscles

We have previously documented a time-course of sarcopenia development in female C57Bl/6J mice, with significant loss of quadriceps muscle mass by 24 m that is more pronounced by 27-29 m. The present study used gastrocnemius muscles from female C57Bl/6J mice aged 3, 15, 24 and 29 months to investigate the expression of genes that coincide with, or potentially precede, muscle loss. The microarray analyses of ageing gastrocnemius muscle indicated that the Functional Theme Protein catabolism was first discernable in 15 and 24 age contrast and then again in the age contrast between 24 m and 29 m. A common Functional Theme in all age contrasts from the microarray analysis was extracellular matrix suggesting continual remodeling of skeletal muscle during ageing. Metabolic traits, particularly those involving altered fatty acid and glucose metabolism were apparent in the contrast between 24 m and 29 m. This may reflect inefficiency of lipid metabolism with ageing caused by altered mitochondrial function, which has been implicated in ageing processes in other studies. There were no functional themes associated with oxidative stress, inflammation or immune cell infiltration in any age contrast, likely indicating that these factors are not primary drivers of sarcopenia. Ageing was also associated with increased global gene expression variance, consistent with generalised decreased control of gene regulation. Microarray profiling was performed in gastrocnemius muscles from female C57Bl/6J mice aged 3, 15, 24 and 29 months.本团队此前已明确雌性C57Bl/6J小鼠肌少症（sarcopenia）的发生时间进程：小鼠于24月龄时已出现显著的股四头肌质量丢失，该表型在27~29月龄时更为显著。本研究选取3、15、24及29月龄雌性C57Bl/6J小鼠的腓肠肌组织，旨在探究与肌肉丢失同步发生或可能早于肌肉丢失的基因表达特征。对衰老腓肠肌的基因芯片（microarray）分析结果显示，蛋白质分解代谢功能主题（Functional Theme）首次在15月龄与24月龄的年龄组对比中被检出，随后在24月龄与29月龄的年龄组对比中再次出现。基因芯片分析的所有年龄组对比中均存在共同的功能主题（Functional Theme）：细胞外基质（extracellular matrix），这提示衰老过程中骨骼肌始终处于持续重塑状态。在24月龄与29月龄的年龄组对比中，代谢特征尤为显著，尤其是涉及脂肪酸与葡萄糖代谢改变的相关通路。该现象可能反映了衰老过程中因线粒体功能（mitochondrial function）改变所导致的脂质代谢效率低下，而线粒体功能异常已在其他研究中被证实与衰老进程密切相关。在所有年龄组对比中均未发现与氧化应激、炎症或免疫细胞浸润相关的功能主题（Functional Theme），这提示上述因素可能并非肌少症发生的核心驱动因素。衰老还与整体基因表达变异度升高相关，这与基因调控的普遍性失控现象相符。本研究的基因芯片分析样本均取自3、15、24及29月龄雌性C57Bl/6J小鼠的腓肠肌组织。