Conserved and species specific molecular denominators in mammalian aging [rat]

Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.衰老是一种复杂的生命现象，涉及多个生理系统的功能衰退。本研究以骨骼肌（skeletal muscle）为研究对象，通过全局基因表达谱（global expression profiles）分析结合衰老进程核心的特异性机制，筛选调控肌肉功能与健康寿命（healthspan）的信号通路。实验设计整合了小鼠、大鼠、恒河猴与人类的跨物种比较分析，并覆盖了各物种生命周期中的三个关键时间节点。随着衰老进程，跨所有物种均出现了与氧化应激（oxidative stress）、炎症反应（inflammation）及营养信号通路（nutrient signaling）相关的信号通路，这些通路协同作用影响线粒体（mitochondria）的质量与状态。值得注意的是，衰老过程中人骨骼肌的线粒体转录本水平（mitochondrial transcript levels）维持得更为稳定，这提示人类在进化层面拥有相较于其他物种更为稳固的适应性。本研究鉴定出的保守通路揭示了健康与寿命共有的内在分子机制；而对物种特异性通路的发掘，则凸显了开展人类研究对于设计延缓衰老的最优治疗策略（therapeutic modalities）的重要性。