Murine Phenotyping Core.
Renal Cellular and Molecular Biology Section, and.
JCI Insight. 2019 Sep 5;4(17):130949. doi: 10.1172/jci.insight.130949.
With increased life expectancy worldwide, there is an urgent need for improving preventive measures that delay the development of age-related degenerative diseases. Here, we report evidence from mouse and human studies that this goal can be achieved by maintaining optimal hydration throughout life. We demonstrate that restricting the amount of drinking water shortens mouse lifespan with no major warning signs up to 14 months of life, followed by sharp deterioration. Mechanistically, water restriction yields stable metabolism remodeling toward metabolic water production with greater food intake and energy expenditure, an elevation of markers of inflammation and coagulation, accelerated decline of neuromuscular coordination, renal glomerular injury, and the development of cardiac fibrosis. In humans, analysis of data from the Atherosclerosis Risk in Communities (ARIC) study revealed that hydration level, assessed at middle age by serum sodium concentration, is associated with markers of coagulation and inflammation and predicts the development of many age-related degenerative diseases 24 years later. The analysis estimates that improving hydration throughout life may greatly decrease the prevalence of degenerative diseases, with the most profound effect on dementia, heart failure (HF), and chronic lung disease (CLD), translating to the development of these diseases in 3 million fewer people in the United States alone.
随着全球预期寿命的延长，迫切需要改进预防措施，以延缓与年龄相关的退行性疾病的发展。在这里，我们报告了来自小鼠和人类研究的证据，表明通过终生保持最佳水合状态可以实现这一目标。我们证明，限制饮水量会导致小鼠寿命缩短，在生命长达 14 个月时没有明显的警告信号，随后急剧恶化。从机制上讲，水限制会导致稳定的代谢重塑，向代谢水生成方向发展，伴随着食物摄入和能量消耗的增加、炎症和凝血标志物的升高、神经肌肉协调性的加速下降、肾肾小球损伤以及心脏纤维化的发展。在人类中，对社区动脉粥样硬化风险（ARIC）研究的数据进行分析表明，通过血清钠浓度在中年评估的水合水平与凝血和炎症标志物有关，并预测 24 年后许多与年龄相关的退行性疾病的发展。分析估计，通过终生改善水合状态可能会大大降低退行性疾病的患病率，对痴呆症、心力衰竭 (HF) 和慢性肺病 (CLD) 的影响最为显著，仅在美国就可减少 300 万人患上这些疾病。
