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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 3

Accelerated impairment of neuromuscular coordination, accumulation of renal glomeruli injuries, and development of cardiac fibrosis in chronically water-restricted (WR) mice.

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Accelerated impairment of neuromuscular coordination, accumulation of re...
(A) WR mice have impaired motor coordination assessed by Rota Rod test at age 14 months. Data are presented as latency to fall versus weight (P = 0.032, ANCOVA for differences between regression lines elevations). (B–E) Renal deterioration is accelerated in WR mice. (B) Representative images of periodic acid-Schiff–stained mid-kidney cross-section and examples of glomeruli for each scoring category used to quantify degree of glomerular injury, from 0 (no injury) to 3 (globally sclerotic glomeruli). The analysis is done after 5 months of water restriction and at the end of lifespan. (C) Number of glomeruli does not change throughout life both in control and WR mice. (D) Proportion of total glomeruli per injury score category. (E) Mean glomeruli injury score. Accumulation of glomerular injury is accelerated in WR mice (mean ± SEM). *P < 0.05; **P < 0.01; ***P < 0.001 by unpaired, 2-tailed t test. (F and G) Water restriction promotes cardiac fibrosis. (F) Images of Masson’s trichrome stain of the heart sections at the end of lifespan. Blue color identifies collagen fibers. Bottom panels: magnifications of fibrotic areas in the heart of WR mice. (G) Quantification of fibrotic areas as percent of total section areas (mean ± SEM). *P < 0.05 by unpaired, 2-tailed t test.

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