enerbol and Neurodegenerative-Diseases

Oxyradicals are generally considered harmful byproducts of oxidative metabolism, causing molecular damage in living systems. They are implicated in various processes such as mutagenesis, aging, and series of pathological events. Although all this may be justified, evidence is accumulating that it is an oversimplified view of the real situation. We can assume nowadays that the living state of cells and organisms implicitly requires the production of oxyradicals. This idea is supported by experimental facts and arguments as follows. (1) Complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms much before the energy reserves would be exhausted. (2) Construction of the supramolecular organization of the cells (especially of their membranous compounds) requires the cross-linking effect of oxyradicals, particularly that of OH* radicals. (3) Blast type cells produce much fewer oxyradicals than do differentiated ones, and interventions increasing the production of OH* radicals induce differentiation of various lines of leukemic (HL-60 and K562) and normal (fibroblasts, chondroblasts, etc.) cells, while SOD expression increases greatly. (4) It is reasonable to assume that the continuous flux of OH* radicals is prerequisite to maintenance of constant electron delocalization on the proteins, which is a semiconductive phenomenon suggested in 1941 by Szent-Györgyi, but it has never been proven experimentally. It is theoretically possible to describe the function of the synapses as that of a single p-n-p transistor, assuming that the free radical flux maintains electron movements on the subsynaptic structures, while the actual membrane potential is governing the electron flux. This theoretical approach may open completely new possibilities for our understanding of the normal functions of living organisms, such as basic memory mechanisms in brain cells, their aging processes, and therapeutic approaches to many degenerative disorders, such as various types of dementia.

Topics: Action Potentials; Aging; Animals; Carbon; Cell Differentiation; Death; Electron Spin Resonance Spectroscopy; Electrons; Free Radical Scavengers; Free Radicals; Hemoglobins; Humans; Hydroxyl Radical; Life; Macromolecular Substances; Mice; Models, Biological; Neurodegenerative Diseases; Oxidation-Reduction; Oxygen; Oxygen Consumption; Poisons; Potassium Cyanide; Proteins; Reactive Oxygen Species; Semiconductors; Superoxide Dismutase; Transistors, Electronic

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.

Topics: Acute Kidney Injury; Aging; Animals; Atherosclerosis; Biomarkers; Chronic Disease; Dehydration; Dementia; Fibrosis; Heart Failure; Humans; Inflammation; Life; Lung Diseases; Male; Mice; Neurodegenerative Diseases; Organism Hydration Status; Regression Analysis; Risk Factors; Sodium; Water-Electrolyte Balance