Association of Vitamin D Receptor with Longevity and Healthy Aging
Longevity is a multifaceted trait in which variety of genes and environmental factors are involved. Newly, the role of vitamin D has been revived regarding its potential advantage on delaying the aging process. Vitamin D exerts its effect through vitamin D receptor (VDR). VDR-FokI is the only polymorphism which alters the VDR length. We examined the frequency of FokI genotypes in old age population as compared to young adults to determine the discerning genotype of FokI polymorphism leading to longer living. In addition, to highlight the position of FokІ polymorphism in quality of life; a cognitive function assessment was performed. 728 participants participated in this study of which 166 individuals were elderly residents of Kahrizak Charity Foundation. The rest were participants of Iranian Multicenter Osteoporosis Study (IMOS). Genomic DNA was extracted from peripheral blood and VDR genotype was detected by the polymerase chain reaction. The participants in the elderly group underwent a cognitive function assessment. Cognitive function was measured with the mini mental state examination (MMSE). Data were analyzed by SPSS 16.5. The prevalence of ff genotype showed 48% decrease in elderly population as compared to young adults (P=0.06). In addition, F allele was over-represented in the elderly group as compared to controls (P=0.05). Also, "FF" participants of elderly group had higher MMSE as compared to "ff" genotype (18.16Vs17.12). Our data suggest that single nucleotide polymorphisms (SNPs) in FokI may be possibly involved in longevity and cognitive function.
Laplana M, Sánchez-de-la-Torre M, Aguiló A, Casado I, Flores M, Sánchez-Pellicer R, Fibla J. Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes. Biogerontology 2010;11(4):437-46.
Raman M, Milestone AN, Walters JR, Hart AL, Ghosh S. Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer. Therap Adv Gastroenterol 2011;4(1):49-62.
Jiang F, Bao J, Li P, Nicosia SV, Bai W. Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. J Biol Chem 2004;279(51):53213-21.
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 2004;101(49):17312-5.
Carrero JJ, Stenvinkel P, Fellström B, Qureshi AR, Lamb K, Heimbürger O,Barany P, Radhakrishnan K, Lindholm B, Soveri I, Nordfors L, Shiels PG. Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients. J Intern Med. 2008;263(3):302-12.
Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J Clin Nutr 2007;86(5):1420-5.
Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 1997;12(6):915-21.
Norman AW, Bouillon R. Vitamin D nutritional policy needs a vision for the future. Exp Biol Med (Maywood) 2010;235:1034-45.
Newman AB, Walter S, Lunetta KL, Garcia ME, Slagboom PE, Christensen K, Arnold AM, Aspelund T, Aulchenko YS, Benjamin EJ, Christiansen L, D'Agostino RB Sr, Fitzpatrick AL, Franceschini N, Glazer NL, et al. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. J Gerontol A Biol Sci Med Sci 2010;65(5):478-87.
Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC. A ChIPseq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res 2010;20(10):1352-60.
Khashayar P, Meybodi HR, Homami MR, Amini MR, Mohajeri-Tehrani MR, Heshmat R, Larijani B. The discriminative value of various biochemical parameters in detecting varying degrees of vitamin D deficiency in the Iranian population. Clin Lab 2011;57(3-4):163-70.
Larijani B, Moayyeri A, Keshtkar AA, Hossein-Nezhad A, Soltani A, Bahrami A, Omrani GH, Rajabian R, Nabipour I. Peak bone mass of Iranian population: the Iranian Multicenter Osteoporosis Study. J Clin Densitom 2006;9(3):367-74.
Ahangari G, Hossein-Nezhad A, Behzadi H, Maghbooli Z, Larijani B. Vitamin D Receptor gene polymorphism may predict response to vitamin D intake and bone turnover. DARU Journal of Pharmaceutical Sciences 2010;17(Suppl 1):13-19.
Ansari NN, Naghdi S, Hasson S, Valizadeh L, Jalaie S. Validation of a Mini-Mental State Examination (MMSE) for the Persian population: a pilot study. ApplNeuropsychol 2010;17(3):190-5.
Lanske B, Razzaque MS. Vitamin D and aging: old concepts and new insights. J Nutr Biochem 2007;18(12):771-7.
Speer G. [The role of vitamin D in the prevention and the additional therapy of cancers]. Magy Onkol 2010;54(4):303-14.
Hossein-Nezhad A, Ahangari G BH, Maghbooli Z, Larijani B. Vitamin D Receptor gene polymorphism may predict response to vitamin D intake and bone turnover. DARU,Suppl 1. 2009;17:13-9.
Park K, Woo M, Nam J, Kim JC. Start codon polymorphisms in the vitamin D receptor and colorectal cancer risk. Cancer Lett 2006;237(2):199-206.
Kostner K, Denzer N, Muller CS, Klein R, Tilgen W,Reichrath J. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Anticancer Res 2009;29(9):3511-36.
Sinotte M, Rousseau F, Ayotte P, Dewailly E, Diorio C, Giguere Y, Bérubé S, Brisson J. Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population. Endocr Relat Cancer.2008;15(4):975-83.
Amato M, Pacini S, Aterini S, Punzi T, Gulisano M, Ruggiero M. Iron indices and vitamin D receptorpolymorphisms in hemodialysis patients. Adv Chronic Kidney Dis 2008;15(2):186-90.
Simon KC, Munger KL, Xing Y, Ascherio A. Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis. Mult Scler 2010;16(2):133-8. PMCID: 2819633.
Chen RH, Chang CT, Chen HY, Chen WC, Tsai CH, Tsai FJ. Association between vitamin-D receptor gene FokI polymorphism and Graves' disease among Taiwanese Chinese. J Clin Lab Anal 2007;21(3):173-7.
Raimondi S, Johansson H, Maisonneuve P, Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis2009;30(7):1170-80.
Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J. A prospective study of plasma vitamin D metabolites, vitamin D receptorpolymorphisms, and prostate cancer. PLoS Med. 2007;4(3):e103. PMCID: 1831738.
Kuningas M, Mooijaart SP, Jolles J, Slagboom PE, Westendorp RG, van Heemst D. VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiol Aging 2009;30(3):466-73.
Marchesi VT. Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy. FASEB J 2011;25(1):5-13.
Slinin Y, Paudel ML, Taylor BC, Fink HA, Ishani A, Canales MT, Canales MT, Yaffe K, Barrett-Connor E, Orwoll ES, Shikany JM, Leblanc ES, Cauley JA, Ensrud KE. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010;74(1):33-41.
Annweiler C, Allali G, Allain P, Bridenbaugh S, Schott AM, Kressig RW, Beauchet O. Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 2009;16(10):1083-9.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.