Institute for Biomechanics, ETH Zurich, Switzerland.
AO Research Institute Davos, Switzerland.
FEBS Open Bio. 2024 Oct;14(10):1668-1681. doi: 10.1002/2211-5463.13866. Epub 2024 Jul 28.
Ageing is an inherent and intricate biological process that takes place in living organisms as time progresses. It involves the decline of multiple physiological functions, leading to body structure and overall performance modifications. The ageing process differs among individuals and is influenced by various factors, including lifestyle, environment and genetic makeup. Metabolic changes and reduced locomotor activity are common hallmarks of ageing. Our study focuses on exploring these phenomena in prematurely ageing PolgA mice (also known as PolgA) aged 41-42 weeks, as they closely mimic human ageing. We assess parameters such as oxygen consumption (VO), carbon dioxide production (VCO), respiratory exchange ratio (RER) and locomotor activity using a metabolic cage for 4 days and comparing them with age-matched wild-type littermates (WT). Our findings revealed that VO, VCO, RER, locomotor activities, water intake and feeding behaviour show a daily rhythm, aligning with roughly a 24-h cycle. We observed that the RER was significantly increased in PolgA mice compared to WT mice during the night-time of the light-dark cycle, suggesting a shift towards a higher reliance on carbohydrate metabolism due to more food intake during the active phase. Additionally, female PolgA mice displayed a distinct phenotype with reduced walking speed, walking distance, body weight and grip strength in comparison to male PolgA and WT mice, indicating an early sign of ageing. Taken together, our research highlights the impact of sex-specific patterns on ageing traits in PolgA mice aged 41-42 weeks, which may be attributable to human ageing phenotypes. The unique genetic composition and accelerated ageing characteristics of PolgA mice make them invaluable in ageing studies, facilitating the investigation of underlying biological mechanisms and the identification of potential therapeutic targets for age-related diseases.
衰老是一个内在而复杂的生物学过程，随着时间的推移，它发生在生物体中。它涉及到多个生理功能的下降，导致身体结构和整体性能的改变。衰老过程在个体之间有所不同，并受到生活方式、环境和遗传因素的影响。代谢变化和运动活动减少是衰老的常见特征。我们的研究集中在探索 41-42 周龄过早衰老的 PolgA 小鼠（也称为 PolgA）中的这些现象，因为它们与人类衰老非常相似。我们使用代谢笼评估了 4 天的耗氧量（VO）、二氧化碳产生量（VCO）、呼吸交换率（RER）和运动活动等参数，并将其与年龄匹配的野生型同窝仔鼠（WT）进行了比较。我们的研究结果表明，VO、VCO、RER、运动活动、水摄入量和摄食行为呈现出一种日常节律，大致与 24 小时周期相吻合。我们观察到，在光-暗周期的夜间，PolgA 小鼠的 RER 与 WT 小鼠相比显著升高，这表明由于在活动期摄入更多的食物，它们对碳水化合物代谢的依赖程度更高。此外，与雄性 PolgA 和 WT 小鼠相比，雌性 PolgA 小鼠的行走速度、行走距离、体重和握力明显降低，这表明它们出现了早期衰老的迹象。综上所述，我们的研究强调了性别特异性模式对 41-42 周龄 PolgA 小鼠衰老特征的影响，这可能归因于人类衰老表型。PolgA 小鼠独特的遗传组成和加速衰老的特征使它们在衰老研究中具有重要价值，有助于研究潜在的生物学机制，并确定与年龄相关疾病的潜在治疗靶点。
