Centenarians have good Vitamin D Receptor genes (or take lots of vitamin D) – March 2016

Impact of vitamin D receptor polymorphisms in centenarians

Cristina Gussago , Beatrice Arosio , Franca Rosa Guerini, Evelyn Ferri, Andrea Saul Costa, Martina Casati, Elisa Mariadele Bollini, Francesco Ronchetti, Elena Colombo and 3 more
Endocrine, pp 1-7, First online: 08 March 2016

Vitamin D is a seco-sterol produced endogenously in the skin or obtained from certain foods. It exerts its action through binding to intracellular vitamin D receptor (VDR). Lately, the role of vitamin D has been revised regarding its potential advantage on delaying the process of aging. The aim of this study was to assess the contribution of VDR gene polymorphisms in healthy aging and longevity.
We evaluated the frequency of four polymorphisms of the VDR gene (FokI, BsmI, ApaI, and TaqI) in centenarians (102 subjects, mean age: 102.3 ± 0.3 years), compared to septuagenarians (163 subjects, mean age: 73.0 ± 0.6 years) and we analyzed a variety of pathophysiologically relevant functions in centenarians. BsmI and ApaI provided a significant association with longevity: there was a highly significant difference in the frequency of

• BsmI genotypes (p = 0.037),
• ApaI genotypes (p = 0.022), and
• ApaI alleles (p = 0.050)

in centenarians versus septuagenarians. Furthermore, we found a significant correlation of all the VDR gene polymorphisms in centenarians with some measured variables such as

• hand grip strength,
• body mass index,
• blood pressure,
• HDL cholesterol, and
• mini-mental state examination.

We also found a correlation with the prevalence of medical history of

• hypertension,
• acute myocardial infarction,
• angina,
• venous insufficiency,
• dementia,
• chronic obstructive pulmonary disease, and
• arthrosis.

In conclusion, this study proposes a new scenario in which the variability of the VDR gene is relevant in the aging process and emphasizes the role of VDR genetic background in determining healthy aging.

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References

• 1. B. Lehmann, The vitamin D3 pathway in human skin and its role for regulation of biological processes. Photochem. Photobiol. 81(6), 1246–1251 (2005). doi:10.​1562/​2005-02-02-IR-430 CrossRefPubMed
• 2. A. Prentice, G.R. Goldberg, I. Schoenmakers, Vitamin D across the lifecycle: physiology and biomarkers. Am. J. Clin. Nutr. 88(2), 500S–506S (2008)PubMed
• 3. S. Kato, K. Takeyama, S. Kitanaka, A. Murayama, K. Sekine, T. Yoshizawa, In vivo function of VDR in gene expression-VDR knock-out mice. J. Steroid Biochem. Mol. Biol. 69(1–6), 247–251 (1999)CrossRefPubMed
• 4. L.P. Freedman, V. Arce, R. Perez Fernandez, DNA sequences that act as high affinity targets for the vitamin D3 receptor in the absence of the retinoid X receptor. Mol. Endocrinol. 8(3), 265–273 (1994). doi:10.​1210/​mend.​8.​3.​8015545 PubMed
• 5. M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357(3), 266–281 (2007). doi:10.​1056/​NEJMra070553 CrossRefPubMed
• 6. R. Bouillon, G. Carmeliet, L. Verlinden, E. van Etten, A. Verstuyf, H.F. Luderer, L. Lieben, C. Mathieu, M. Demay, Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29(6), 726–776 (2008). doi:10.​1210/​er.​2008-0004 CrossRefPubMedPubMedCentral
• 7. B. Schottker, U. Haug, L. Schomburg, J. Kohrle, L. Perna, H. Muller, B. Holleczek, H. Brenner, Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am. J. Clin. Nutr. 97(4), 782–793 (2013). doi:10.​3945/​ajcn.​112.​047712 CrossRefPubMed
• 8. E.P. Cherniack, B.R. Troen, H.J. Florez, B.A. Roos, S. Levis, Some new food for thought: the role of vitamin D in the mental health of older adults. Curr Psychiatry Rep 11(1), 12–19 (2009)CrossRefPubMed
• 9. J.M. Valdivielso, E. Fernandez, Vitamin D receptor polymorphisms and diseases. Clin. Chim. Acta 371(1–2), 1–12 (2006). doi:10.​1016/​j.​cca.​2006.​02.​016 CrossRefPubMed
• 10. M. Meehan, S. Penckofer, The role of vitamin D in the aging adult. J Aging Gerontol 2(2), 60–71 (2014). doi:10.​12974/​2309-6128.​2014.​02.​02.​1 CrossRefPubMedPubMedCentral
• 11. B. Schottker, R. Jorde, A. Peasey, B. Thorand, E.H. Jansen, L. Groot, M. Streppel, J. Gardiner, J.M. Ordonez-Mena, L. Perna, T. Wilsgaard, W. Rathmann, E. Feskens, E. Kampman, G. Siganos, I. Njolstad, E.B. Mathiesen, R. Kubinova, A. Pajak, R. Topor-Madry, A. Tamosiunas, M. Hughes, F. Kee, M. Bobak, A. Trichopoulou, P. Boffetta, H. Brenner, Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ 348, g3656 (2014). doi:10.​1136/​bmj.​g3656 CrossRefPubMedPubMedCentral
• 12. B. Lanske, M.S. Razzaque, Vitamin D and aging: old concepts and new insights. J. Nutr. Biochem. 18(12), 771–777 (2007). doi:10.​1016/​j.​jnutbio.​2007.​02.​002 CrossRefPubMedPubMedCentral
• 13. J.B. Richards, A.M. Valdes, J.P. Gardner, D. Paximadas, M. Kimura, A. Nessa, X. Lu, G.L. Surdulescu, R. Swaminathan, T.D. Spector, A. Aviv, Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am. J. Clin. Nutr. 86(5), 1420–1425 (2007)PubMedPubMedCentral
• 14. A.W. Norman, R. Bouillon, Vitamin D nutritional policy needs a vision for the future. Exp Biol Med (Maywood) 235(9), 1034–1045 (2010). doi:10.​1258/​ebm.​2010.​010014 CrossRef
• 15. I. Pusceddu, C.J. Farrell, A.M. Di Pierro, E. Jani, W. Herrmann, M. Herrmann, The role of telomeres and vitamin D in cellular aging and age-related diseases. Clin. Chem. Lab. Med. (2015). doi:10.​1515/​cclm-2014-1184 PubMed
• 16. J.J. McGrath, S. Saha, T.H. Burne, D.W. Eyles, A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations. J. Steroid Biochem. Mol. Biol. 121(1–2), 471–477 (2010). doi:10.​1016/​j.​jsbmb.​2010.​03.​073 CrossRefPubMed
• 17. L. Laczmanski, M. Jakubik, G. Bednarek-Tupikowska, J. Rymaszewska, N. Sloka, F. Lwow, Vitamin D receptor gene polymorphisms in Alzheimer’s disease patients. Exp. Gerontol. 69, 142–147 (2015). doi:10.​1016/​j.​exger.​2015.​06.​012 CrossRefPubMed
• 18. A.G. Uitterlinden, Y. Fang, J.B. van Meurs, H. van Leeuwen, H.A. Pols, Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J. Steroid Biochem. Mol. Biol. 89–90(1–5), 187–193 (2004). doi:10.​1016/​j.​jsbmb.​2004.​03.​083 CrossRefPubMed
• 19. M. Laplana, M. Sanchez-de-la-Torre, A. Aguilo, I. Casado, M. Flores, R. Sanchez-Pellicer, J. Fibla, Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes. Biogerontology 11(4), 437–446 (2010). doi:10.​1007/​s10522-010-9273-8 CrossRefPubMed
• 20. V.F. Najmi, F. Sharifi, A. Hossein-Nezhad, M. Mirarefin, Z. Maghbooli, M. Ghaderpanahi, B. Larijani, H. Fakhrzadeh, Association of vitamin D receptor with longevity and healthy aging. Acta Med Iran 51(4), 236–241 (2013)
• 21. C. Franceschi, L. Motta, S. Valensin, R. Rapisarda, A. Franzone, M. Berardelli, M. Motta, D. Monti, M. Bonafe, L. Ferrucci, L. Deiana, G.M. Pes, C. Carru, M.S. Desole, C. Barbi, G. Sartoni, C. Gemelli, F. Lescai, F. Olivieri, F. Marchegiani, M. Cardelli, L. Cavallone, P. Gueresi, A. Cossarizza, L. Troiano, G. Pini, P. Sansoni, G. Passeri, R. Lisa, L. Spazzafumo, L. Amadio, S. Giunta, R. Stecconi, R. Morresi, C. Viticchi, R. Mattace, G. De Benedictis, G. Baggio, Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians (IMUSCE). Aging (Milano) 12(2), 77–84 (2000)
• 22. M.P. Lawton, E.M. Brody, Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9(3), 179–186 (1969)CrossRefPubMed
• 23. S. Katz, A.B. Ford, R.W. Moskowitz, B.A. Jackson, M.W. Jaffe, Studies of illness in the aged. The index of Adl: a standardized measure of biological and psychosocial function. JAMA 185, 914–919 (1963)CrossRefPubMed
• 24. S.A. Miller, D.D. Dykes, H.F. Polesky, A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16(3), 1215 (1988)CrossRefPubMedPubMedCentral
• 25. S.H. Abd-Allah, H.F. Pasha, H.A. Hagrass, A.A. Alghobashy, Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene 536(2), 430–434 (2014). doi:10.​1016/​j.​gene.​2013.​12.​032 CrossRefPubMed
• 26. S.W. Guo, V.L. Magnuson, J.J. Schiller, X. Wang, Y. Wu, S. Ghosh, Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies. Am. J. Epidemiol. 164(8), 711–724 (2006). doi:10.​1093/​aje/​kwj278 CrossRefPubMed
• 27. B. Gyorffy, B. Vasarhelyi, D. Krikovszky, L. Madacsy, A. Tordai, T. Tulassay, A. Szabo, Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Eur. J. Endocrinol. 147(6), 803–808 (2002)CrossRefPubMed
• 28. M. Glocke, F. Lang, E. Schaeffeler, T. Lang, M. Schwab, U.E. Lang, Impact of vitamin D receptor VDR rs2228570 polymorphism in oldest old. Kidney Blood Press Res 37(4–5), 311–322 (2013). doi:10.​1159/​000350159 CrossRefPubMed
• 29. L.A. Beveridge, M.D. Witham, Controversy in the link between vitamin D supplementation and hypertension. Exp Rev Cardiovasc Ther 13, 1–3 (2015). doi:10.​1586/​14779072.​2015.​1065729 CrossRef
• 30. R. Richmond, J. Law, F. Kay-Lambkin, Higher blood pressure associated with higher cognition and functionality among centenarians in Australia. Am. J. Hypertens. 24(3), 299–303 (2011). doi:10.​1038/​ajh.​2010.​236 CrossRefPubMed
• 31. S.D. Ostergaard, S. Mukherjee, S.J. Sharp, P. Proitsi, L.A. Lotta, F. Day, J.R. Perry, K.L. Boehme, S. Walter, J.S. Kauwe, L.E. Gibbons, E.B. Larson, J.F. Powell, C. Langenberg, P.K. Crane, N.J. Wareham, R.A. Scott, Associations between potentially modifiable risk factors and Alzheimer disease: a mendelian randomization study. PLoS Med 12(6), e1001841 (2015). doi:10.​1371/​journal.​pmed.​1001841 CrossRefPubMedPubMedCentral
• 32. L.S. Carvalho, A.C. Sposito, Vitamin D for the prevention of cardiovascular disease: are we ready for that? Atherosclerosis 241(2), 729–740 (2015). doi:10.​1016/​j.​atherosclerosis.​2015.​06.​034 CrossRefPubMed
• 33. S. Afzal, S.E. Bojesen, B.G. Nordestgaard, Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 10(3), 296–302 (2014). doi:10.​1016/​j.​jalz.​2013.​05.​1765 CrossRefPubMed
• 34. D. Gezen-Ak, S. Yilmazer, E. Dursun, Why vitamin D in Alzheimer’s disease? The hypothesis. J Alzheimers Dis 40(2), 257–269 (2014). doi:10.​3233/​JAD-131970 PubMed
• 35. T.J. Littlejohns, W.E. Henley, I.A. Lang, C. Annweiler, O. Beauchet, P.H. Chaves, L. Fried, B.R. Kestenbaum, L.H. Kuller, K.M. Langa, O.L. Lopez, K. Kos, M. Soni, D.J. Llewellyn, Vitamin D and the risk of dementia and Alzheimer disease. Neurology 83(10), 920–928 (2014). doi:10.​1212/​WNL.​0000000000000755​ CrossRefPubMedPubMedCentral
• 36. E.D. Toffanello, A. Coin, E. Perissinotto, S. Zambon, S. Sarti, N. Veronese, M. De Rui, F. Bolzetta, M.C. Corti, G. Crepaldi, E. Manzato, G. Sergi, Vitamin D deficiency predicts cognitive decline in older men and women: the Pro.V.A. study. Neurology 83(24), 2292–2298 (2014). doi:10.​1212/​WNL.​0000000000001080​ CrossRefPubMed
• 37. E. Jakubowska-Pietkiewicz, W. Mlynarski, I. Klich, W. Fendler, D. Chlebna-Sokol, Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients. Mol. Biol. Rep. 39(5), 6243–6250 (2012). doi:10.​1007/​s11033-012-1444-z CrossRefPubMed
• 38. D. Goltzman, D. Miao, D.K. Panda, G.N. Hendy, Effects of calcium and of the vitamin D system on skeletal and calcium homeostasis: lessons from genetic models. J. Steroid Biochem. Mol. Biol. 89–90(1–5), 485–489 (2004). doi:10.​1016/​j.​jsbmb.​2004.​03.​058 CrossRefPubMed
• 39. J.L. Castrillon, G. Diaz-Soto, O.I. Jauregui, E. Romero, D. de Luis Roman, Polymorphisms of the vitamin D receptor and their effect on bone mass density in patients with normocalcemic hyperparathyroidism. Endocrine 50(3), 816–818 (2015). doi:10.​1007/​s12020-015-0611-0 CrossRefPubMed
• 40. Z.H. Zhu, X.Z. Jin, W. Zhang, M. Chen, D.Q. Ye, Y. Zhai, F.L. Dong, C.L. Shen, C. Ding, Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis. Rheumatology (Oxford) 53(6), 998–1008 (2014). doi:10.​1093/​rheumatology/​ket418 CrossRef
• 41. M. Feng, H. Li, S.F. Chen, W.F. Li, F.B. Zhang, Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine 43(2), 318–326 (2013). doi:10.​1007/​s12020-012-9812-y CrossRefPubMed
• 42. A.M. Wood, C. Bassford, D. Webster, P. Newby, P. Rajesh, R.A. Stockley, D.R. Thickett, Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages. Thorax 66(3), 205–210 (2011). doi:10.​1136/​thx.​2010.​140921 CrossRefPubMed
• 43. T. Yumrutepe, Z.A. Aytemur, O. Baysal, H. Taskapan, C.M. Taskapan, S.S. Hacievliyagil, Relationship between vitamin D and lung function, physical performance and balance on patients with stage I-III chronic obstructive pulmonary disease. Rev. Assoc. Med. Bras. 61(2), 132–138 (2015). doi:10.​1590/​1806-9282.​61.​02.​132 CrossRefPubMed
• 44. R.J. Gobbens, M.A. van Assen, K.G. Luijkx, M.T. Wijnen-Sponselee, J.M. Schols, The Tilburg Frailty Indicator: psychometric properties. J. Am. Med. Dir. Assoc. 11(5), 344–355 (2010). doi:10.​1016/​j.​jamda.​2009.​11.​003 CrossRefPubMed
• 45. F.Y. Wu, C.S. Liu, L.N. Liao, C.I. Li, C.H. Lin, C.W. Yang, N.H. Meng, W.Y. Lin, C.K. Chang, J.H. Hsiao, T.C. Li, C.C. Lin, Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E). Osteoporos. Int. 25(7), 1917–1929 (2014). doi:10.​1007/​s00198-014-2691-8 CrossRefPubMed
• 46. A. Haslam, M.A. Johnson, D.B. Hausman, M.E. Cress, D.K. Houston, A. Davey, L.W. Poon, Vitamin D status is associated with grip strength in centenarians. J Nutr Gerontol Geriatr 33(1), 35–46 (2014). doi:10.​1080/​21551197.​2013.​867825 CrossRefPubMed