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Suboptimal hydration remodels metabolism, promotes degenerative diseases, and shortens life
Michele D. Allen, … , Manfred Boehm, Natalia I. Dmitrieva
Michele D. Allen, … , Manfred Boehm, Natalia I. Dmitrieva
Published September 5, 2019
Citation Information: JCI Insight. 2019;4(17):e130949. https://doi.org/10.1172/jci.insight.130949.
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Research Article Aging

Suboptimal hydration remodels metabolism, promotes degenerative diseases, and shortens life

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Abstract

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.

Authors

Michele D. Allen, Danielle A. Springer, Maurice B. Burg, Manfred Boehm, Natalia I. Dmitrieva

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Figure 4

Hydration status assessed by serum sodium concentration at middle age is associated with markers of inflammation and coagulation and predicts development of age-related degenerative diseases 24 years later: Atherosclerosis Risk in Communities (ARIC) study.

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Hydration status assessed by serum sodium concentration at middle age is...
(A) Overview of ARIC study. ARIC is a prospective epidemiologic study that recruited 45- to 64-year-old participants (15,792 total) in 1987–1989 and followed them for 24 years. The follow-up included 4 additional visits and telephone interviews. Current analysis included participants who had all analyzed variables available, had average serum sodium concentration from visits 1 and 2 within reference range of 135–146 mmol/L and average glucose concentration at visits 1 and 2 lower than 126 mg/dL. In all, 4,602 participants remained for the analysis. (B–F) 3D mesh plots, visualizing continuous variables as functions of serum sodium concentration and age observed in the ARIC study participants. See Table 1 for results of formal linear regression analyses and Supplemental Figure 4 for distributions of the variables. Participants with higher serum sodium levels (B and C) had increased level of acute-phase proteins fibrinogen and factor VIII at visit 1, (D) had higher level of vWF at visit 1, (E) did not change white blood cell count (WBC), (F) had higher level of C-reactive protein (CRP) at visit 4, (G and H) showed faster decline in estimated glomerular filtration rate (eGFR) with age, and (I) lost weight during last 15 years of follow-up (between visits 5 and 4). (J and K) Prevalence of diseases in ARIC study participants at visit 5 depending on average serum sodium concentration measured at visits 1 and 2. (J) Distribution histogram of average serum sodium concentration on visits 1 and 2 in ARIC study participants included in the analysis. Participants are divided into 4 groups based on their serum sodium concentrations. (K) Prevalence of the diseases in the groups with different serum sodium concentrations. Higher sodium is associated with higher prevalence of many chronic diseases with highest prevalence in the 143–146 mmol/L group for all diseases except asthma and peripheral vascular disease (PVD) and with a sharp increase at 142 mmol/L for dementia, heart failure, and chronic lung diseases. See Table 1 and Supplemental Table 2 for results of formal logistic regression analyses.

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