Vitamin D and aging.
- this is the single result from May 2010 Pubmed search Limits Activated: Humans, Meta-Analysis, Randomized Controlled Trial, Review, English, Field: Title/Abstract
J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):78-84. Tuohimaa P.
Medical School, 33014 University of Tampere, Finland. pentti.tuohimaa at uta.fi
Recent studies using genetically modified mice, such as FGF23-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan. The phenotype reversed by normalizing vitamin D and/or mineral homeostasis.
Thus, hypervitaminosis D due to an increased 1alpha-hydroxylase activity seems to be a cause of the premature aging. In several studies, we have described that a complete or partial lack of vitamin D action (VDR-/- mice and CYP27B1-/-) show almost similar phenotype as FGF23-/- or Klotho-/- mice. VDR mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. CYP27B1-/- mice do not show alopecia nor balance deficit, which might be apoVDR-dependent or calcidiol-dependent.
The features are typical to premature aging. The phenotype is resistant to a normalization of the mineral homeostasis by a rescue diet containing high calcium and phosphate. Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone.
Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-DBP by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol.
Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer.
Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk. Therefore, it is necessary to study several common aging-associated diseases such as osteoporosis, hypertension and diabetes known to be vitamin D-dependent before any recommendations of an optimal serum concentration of calcidiol are given. PMID: 19444937
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See also in Vitamin D Life
items on Mortality and vitamin D
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New book coming out Dec 2010
The Immortality Edge: Realize the Secrets of Your Telomeres for a Longer, Healthier Life
Has many items on vitamin D
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Earlier article
Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women1,2,3
J Brent Richards, Ana M Valdes, Jeffrey P Gardner, Dimitri Paximadas, Masayuki Kimura, Ayrun Nessa, Xiaobin Lu, Gabriela L Surdulescu, Rami Swaminathan, Tim D Spector and Abraham Aviv
1 From Twin Research and Genetic Epidemiology, St Thomas’ Hospital, King's College, London School of Medicine, London, United Kingdom (JBR, AMV, DP, AN, GLS, and TDS); the Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, Newark, NJ (JPG, MK, XL, and AA); and the Department of Chemical Pathology, St Thomas’ Hospital, London, United Kingdom (RS)
Background: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.
Objective: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.
Design: Serum vitamin D concentrations were measured in 2160 women aged 18–79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.
Results: Age was negatively correlated with LTL (r = –0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.
Conclusion: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.