Early cardiac ageing: Phenotypic and transcriptional transitions in young to middle-aged mice. Early cardiac ageing: Phenotypic and transcriptional transitions in young to middle-aged mice

While much research has focussed on advanced stages (and mechanisms) of ageing, this fundamental process may commence at a relatively early age, impacting organ function and resilience throughout the adult lifespan. In male C57BL/6 mice, multiple phenotypic and transcriptional features of cardiovascular ageing were evident from 16 weeks of age, well in advance of 'middle age'. Phenotypic changes include declining cardiac and coronary reserves and resistance to ischaemic insult. Gene changes support early constitutive stress together with a plateau in transcriptome responsiveness to ischaemia, and declining induction of cardioprotective and quality control pathways vs. increasing induction of genes promoting signalling dysfunction, hypertrophy and cell death. These findings support cardiac ageing from early adulthood. Molecular changes reflect declining adaptive capacity/quality control, consistent with evolutionary theories of biological ageing. Overall design: Total RNA obtained from isolated left ventricular myocardium of aged male mice (8wk, 16wk, 32wk, 48wk), tissue collected pre- and post-ischemia (n=6/group)

尽管已有大量研究聚焦于衰老的晚期阶段（及其机制），但这一基础生理过程可能在相对较早的年龄便已启动，并会在整个成年生命周期中持续影响器官功能与抗逆能力。在雄性C57BL/6小鼠中，心血管衰老的多种表型与转录特征早在16周龄便已显现，远早于所谓的“中年”阶段。表型变化包括心脏与冠脉储备功能下降，以及对缺血损伤（ischaemic insult）的抵抗能力降低。基因表达变化则表明，小鼠体内存在早期持续性应激，同时转录组（transcriptome）对缺血的应答反应进入平台期；心脏保护通路与质量控制通路的诱导表达水平逐渐下降，而促进信号通路功能异常、心肌肥大（hypertrophy）与细胞死亡的基因的诱导表达则逐渐增强。上述研究结果证实，心脏衰老可始于成年早期。实验整体设计：从不同周龄雄性小鼠（8周、16周、32周、48周）的分离左心室心肌组织（left ventricular myocardium）中提取总RNA，分别采集缺血前与缺血后的组织样本（每组6只）