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P. Tuohimaa

J Aging Res Clin Practice 2012;1(3):256-268

Aging is a complex event and several separate molecular mechanisms lead to the same endpoint, normal or premature senescence. The interrelationships between different signaling systems involved in aging remain speculative. Aging is characterized by gradual loss of stress tolerance due to an accumulation of DNA and protein damages. According to a dominating hypothesis the damages are caused by the oxidative stress. The repair mechanisms, anti-oxidative enzymes, IGF signaling, sirtuins and NFκB play an important role in the premature aging. Vitamin D is a prohormone and currently there are at least three cholecalciferol hormones (CHs): 1α-calcitriol (1α,25(OH)2D3), calcidiol (25OHD3) and 24-calcitriol (24,25(OH)2D3). A combination of 1α-calcitriol and calcidiol seems to act synergistically in the target cells regulating several functions including aging. The physiological circulating levels of calcidiol or 1α-calcitriol alone are not sufficient for biological responses. There is a reciprocal relationship between these metabolites (a negative feedback control), which seems to regulate the endocrine balance of CHs. CHs have been demonstrated to be key factors in the regulation of most of these mediators and therefore they play a central role in aging. It seems that an optimal calcidiol serum concentration might delay aging. On the contrary, calcidiol imbalance may lead to a premature aging and earlier appearance of chronic diseases (osteoporosis, cancer, atherosclerosis, neurodegenerative disorders etc) as a sign of aging. Epidemiological studies on the role of hormonal forms of vitamin D3 in chronic diseases are inconsistent. There are several reasons to this inconsistency and one of the reasons might be a non-linear dependency on calcidiol serum concentrations. A U- or J-shaped risk curve is typical to hormones such as steroids, thyroid hormones, retinoids as well as cholecalciferol hormones. The phenomen is known as hormesis. CHs seem to have harmful effects on health and accelerate aging both at low and high serum concentrations. This suggests that there is an optimal serum concentration of calcidiol, which delays aging. The elderly people are in a high risk of vitamin D insufficiency with aging (cholecalciferolpause), because they are not exposed to sun and their skin has a low capacity to produce vitamin D3. Selected studies based on several health outcomes suggest that the optimum is between 40-80 nmol/ L (16-32 ng/ml). This level is reached, if the daily vitamin D dose in the elderly is 10-20 μg. However, more studies are needed on several common degenerative diseases, before the final vitamin D recommendations to elderly can be made.

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