Abstract
Within the past three to four decades a revolution has occurred in our understanding of vitamin D and its effects. Sundry laboratory and epidemiologic studies have revealed that the active metabolite of vitamin D controls and/or ameliorates various pathologies. As presented here, there is substantive evidence that vitamin D may play a positive and important role in the ageing process. This evidence arises from detailed consideration of various biological mechanisms and processes by which vitamin D operates as well as specific examples of its exerting control/amelioration of various human maladies which contribute to ageing. Arguments are advanced that vitamin D appears to play a major positive role in biogerontology by reducing susceptibility in the elderly to chronic degenerative diseases. It is strongly recommended that the positive role of vitamin D in ageing be taken into account by gerontologists and biogerontology researchers.
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References
Abete P, Calabrese E, Ji LL et al (2008) Mild stress and healthy aging: perspectives for human beings. In: Le Bourg E, Rattan SIS (eds) Mild stress and healthy aging. Springer, Berlin, pp 171–183
Adams JS, Liu PT, Chun R et al (2007) Vitamin D in defense of the human immune response. Ann N Y Acad Sci 1117:94–105
Andjelkovic Z, Vojinovic J, Pejnovic N et al (1999) Disease modifying and immunomodulatory effects of high dose of 1α(OH) D3 in rheumatoid arthritis patients. Clin Exp Rheumatol 17:453–456
Armas LA, Hollis BW, Heaney RP (2004) Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89:5387–5391
Aubin JE, Heersche JNM (1997) Vitamin D and osteoblasts. In: Feldman D, Glorieux FH, Pike JW (eds) Vitamin D. Academic Press, San Diego, pp 313–328
Autier P, Gandini S (2007) Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 167:1730–1737
Banerjee P, Chatterjee M (2003) Antiproliferative role of vitamin D and its analogs—a brief review. Mol Cell Biochem 253:247–254
Bao B-Y, Ting H-J, Hsu J-W et al (2008) Protective role of 1α, 25-dihydroxyvitamin D3 against sensitive oxidative stress in nonmalignant human prostate epithelial cells. Int J Cancer 122:2699–2706
Bernardi RJ, Johnson CS, Modzelewski RA et al (2002) Antiproliferative effects of 1α, 25-dihydroxyvitamin D3 and vitamin D analogs on tumor-derived endothelial cells. Endocrinology 143:2508–2514
Blum M, Dolnikowski G, Seyoum D et al (2008) Vitamin D3 in fat tissue. Endocrine 33:90–94
Bouillon R, Okamura WH, Norman AW (1995) Structure-function relationships in the vitamin D endocrine system. Endocrin Rev 16:200–257
Bursch W, Ellinger A (2005) Autophagy—a basic mechanism and a potential role for neurodegeneration. Folia Neuropathol 43:297–310
Bursch W, Ellinger A, Gerner CH et al (2000) Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? Ann N Y Acad Sci 926:1–12
Cannell JJ, Vieth R, Umhau JC et al (2006) Epidemic influenza and vitamin D. Epidemiol Infect 134:1129–1140
Cannell JJ, Hollis BW, Zasloff M et al (2008) Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother 9:107–118
Cantorna MT (2006) Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 92:60–64
Cantorna MT, Mahon BM (2004) Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood) 229:1136–1142
Cantorna MT, Zhu Y, Froicu M et al (2004) Vitamin D status, 1, 25-dihydroxyviatmin D3, and the immune system. Am J Clin Nutr 80(6 Suppl):1717S–1720S
Capri M, Monti D, Salvioli S et al (2006) Complexity of anti-immunosenescence strategies in humans. Artif Organs 30:730–742
Chandra J, Samali A, Orrenius S (2000) Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med 29:323–333
Chatterjee M (2001) Vitamin D and genomic stability. Mutat Res 475:69–87
Chen K-B, Lin AM-Y, Chiu T-S (2003) Systematic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain. Ann N Y Acad Sci 993:313–324
Chuck A, Todd J, Diffey B (2001) Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photodermatol Photoimmunol Photomed 17:168–171
Clairmont A, Tessman D, Stock A et al (1996) Induction of gap junctional intercellular communication by vitamin D in human skin fibroblasts is dependent on the nuclear vitamin D receptor. Carcinogenesis 17:1389–1391
Danielsson C, Mathiasen IS, James SY et al (1997) Sensitive induction of apoptosis by a novel 1, 25-dihydroxyvitamin D3 analogue shows relation to promoter selectivity. J Cell Biochem 66:552–562
Davis CD (2008) Vitamin D and cancer: current dilemmas and future research needs. Am J Clin Nutr 88:565S–569S
Dawson-Hughes B (2008) Serum 25-hydroxyvitain D and functional outcomes in the elderly. Am J Clin Nutr 88:537S–540S
Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7:684–700
DeLuca HF (1997) Historical overview. In: Feldman D, Glorieux FH, Pike JW (eds) Vitamin D. Academic Press, San Diego, pp 3–12
DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80(6 Suppl):1689S–1696S
DeLuca HF, Cantorna MT (2001) Vitamin D: its role and uses in immunology. FASEB J 15:2579–2585
DeLuca HF, Zierold C (1998) Mechanisms and functions of vitamin D. Nutr Rev 56(2 Pt 2):S4–S10
Dusso AS, Brown AJ, Slatopolsky E (2005) Vitamin D. Am J Physiol Renal Physiol 289:F8–F28
Feldman D, Glorieux FH, Pike JW (eds) (1997) Vitamin D. Academic Press, San Diego
Fernandez-Garcia NI, Palmer HG, Garcia M et al (2005) 1α, 25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells. Oncogene 24:6533–6544
Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nat Med 1:27–31
Franceschi C, Monti D, Scarfi MR et al (1992) Genomic instability and aging. Studies in centenarians (successful aging) and in patients with Down’s syndrome (accelerated aging). Ann N Y Acad Sci 663:4–16
Friedman DS, O’Colmain BJ, Munoz B et al (2004) Prevalence of age-related macular degeneration in the United States. Arch Opthalmol 122:564–572
Froicu M, Cantorna MT (2007) Vitamin D and vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol 8:5
Fujioka T, Suzuki Y, Okamoto T et al (2000) Prevention of renal cell carcinoma by active vitamin D. World J Surg 24:1205–1210
Fujita H, Sugimoto K, Inatomi S et al (2008) Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell 19:1912–1921
Garcion E, Wion-Barbot N, Montero-Menei CN et al (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13:100–105
Gewirtz DA (2007) Autophagy as a mechanism of radiation sensitization in breast tumor cells. Autophagy 3:249–250
Griffin MD, Lutz WH, Phan VA et al (2000) Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun 270:701–708
Halloran BP, Portale AA (1997) Vitamin D metabolism: the effects of aging. In: Feldman D, Glorieux FH, Pike JW (eds) Vitamin D. Academic Press, San Diego, pp 541–554
Hampton MB, Orrenius S (1998) Redox regulation of apoptotic cell death in the immune system. Toxicol Lett 102–103:355–358
Harman D (2006) Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci 1067:10–21
Hayes DP (2007) Nutritional hormesis. Eur J Clin Nutr 61:147–159
Hayes DP (2008a) The protection afforded by vitamin D against low radiation damage. Int J Low Radiat 5:368–394
Hayes DP (2008b) Adverse effects of nutritional inadequacy and excess: a hormetic model. Am J Clin Nutr 88:578S–581S
Higami Y, Shimokawa I (2000) Apoptosis in the aging process. Cell Tissue Res 301:125–132
Holick MF (1995) Noncalcemic actions of 1, 25-dihydroxyvitamin D3 and clinical applications. Bone 17(2 Suppl):107S–111S
Holick MF (ed) (1999) Vitamin D: physiology, molecular biology, and clinical applications. Humana, Totowa
Holick MF (2006) High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353–373
Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281
Hosseinpour F, Wikvall K (2000) Porcine microsomal vitamin D3 25-hydroxylase (CYP2D25). Catalytic properties, tissue distribution, and comparison with human CYP2D6. J Biol Chem 275:34650–34655
Houghton LA, Vieth R (2006) The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 84:694–697
Hoyer-Hansen M, Jaattela M (2007) AMP-activated protein kinase: a universal regulator of autophagy. Autophagy 3:381–383
Hypponen E, Laara E, Reunanen A et al (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–15003
Ji LL (2008) Physical activity: a strong stimulant for hormesis during aging. In: Bourg EL, Rattan SIS (eds) Mild stress and healthy aging. Springer, Berlin, pp 97–114
Johnstone RW, Ruefli AA, Lowe SW (2002) Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:153–164
Lamprecht SA, Lipkin M (2003) Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer 3:601–614
Lappe JM, Travers-Gustafson D, Davies KM et al (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 85:1586–1591
Lin AM, Chen KB, Chao PL (2005) Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS. Ann N Y Acad Sci 1053:319–329
Linnane AW, Kios M, Vitetta L (2007) Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide. Biogerontology 8:445–467
Lips P (2006) Vitamin D physiology. Prog Biophys Mol Biol 92:4–8
Lips P (2007) Relative value of 25(OH)D and 1, 25(OH)2D measurements. J Bone Miner Res 22:1668–1671
Liu PT, Modlin RL (2008) Human macrophage host defense against Mycobacterium tuberculosis. Curr Opin Immun 20:371–376
Llewellyn DJ, Langa K, Lang I (2009) Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol 22:188–199
Lockshin RA, Zakeri ZF (1990) Programmed cell death: new thoughts and relevance to aging. J Gerontol 45:B135–B140
Looker AS, Pfeiffer CM, Lacher DA et al (2008) Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr 88:1519–1527
MacLaughlin J, Holick MF (1985) Aging decreases the capacity of human skin to produce vitamin D. J Clin Invest 76:1536–1538
Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT (2003) Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 134:128–132
Mantell DJ, Owens PE, Bundred NJ et al (2000) 1α, 25-Dihydroxyvitamin D3 inhibits angiogenesis in vitro and in vivo. Circ Res 87:214–220
Marshall TG (2008) Vitamin D discovery outpaces FDA decision making. Bioessays 30:173–182
Masuda S, Jones G (2006) Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol Cancer Ther 5:797–808
Mathew R, White E (2007) Why sick cells produce tumors: the protective role of autophagy. Autophagy 3:502–505
Mathiasen IS, Sergeev IN, Bastholm L et al (2002) Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J Biol Chem 277:30738–30745
Mathieu C, Adorini L (2002) The coming age of 1, 25-dihydroxyvitamin D3 analogs as immunomodulatory agents. Trends Mol Med 8:174–179
May E, Asadullah K, Zugel U (2004) Immunoregulation through 1, 25-dihydroxyvitamin D3 and its analogs. Curr Drug Targets Inflamm Allergy 3:377–393
Minghetti PP, Norman AW (1988) 1, 25(OH)2-vitamin D3 receptors: gene regulation and genetic circuitry. FASEB J 2:3043–3053
Miyashita T, Reed JC (1995) Tumour suppressor p53 is a direct transcriptional activator of human bax gene. Cell 80:293–299
Nagpal S, Na S, Rathnachalam R (2005) Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 26:662–687
Norman AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88:491S–499S
Ofodile ON (2006) Cardiovascular disease could be contained based on currently available data!. Dose-Response 4:225–254
Ohnishi T, Takahashi A, Ohnishi K (2002) Studies about space radiation promote new fields in radiation biology. J Radiat Res (Tokyo) 43(Suppl):S7–S12
Omdahl J, May B (1997) The 25-hydroxyvitamin D 24-hydroxylase. In: Feldman D, Glorieux FH, Pike JW (eds) Vitamin D. Academic Press, San Diego, pp 69–85
Oudshoorn C, Mattace-Raso FU, van der Velde N et al (2008) Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 5:539–543
Overbergh L, Decallone B, Valckx D et al (2000) Identification and immune regulation of 25-hydroxyvitamin D-1-α-hydroxylase in murine macrophages. Clin Exp Immunol 120:139–146
Parekh N, Chappell RJ, Millen AE et al (2007) Association between vitamin D and age-related macular degeneration in the third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol 125:661–669
Payne ME, Anderson JJB, Steffens DC (2008) Calcium and vitamin D intakes may be positively associated with brain lesions in depressed and nondepressed elders. Nutr Res 28:285–292
Penna G, Adorini L (2000) 1α25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405–2411
Pepper M (1997) Manipulating angiogenesis. From basic science to the bedside. Arterioscler Thromb Vasc Biol 17:605–619
Pike JW (1985) Intracellular receptors mediate the biologic action of 1, 25-dihydroxyvitamin D3. Nutr Rev 43:161–168
Prentice A (2008) Vitamin D deficiency: a global perspective. Nutr Rev 66(10 Suppl 2):S153–S164
Ravikumar B, Rubinsztein DC (2006) Role of autophagy in the clearance of mutant huntingtin: a step towards therapy? Mol Aspects Med 27:520–527
Regulska M, Leskiewicz M, Budziszewska B et al (2006) Involvement of P13-K in neuroprotective effects of 1, 25-dihydroxyvitamin D3 analogue—PRI-2191. Pharmacol Rep 58:900–907
Rieux-Laucat F, Le Deist F, Hivroz C et al (1995) Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268:1347–1349
Salganik RI (2001) The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 20(5 Suppl):4645–4728
Schleithoff SS, Zittermann A, Tenderich G et al (2006) Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 83:754–759
Scragg R, Camargo CA Jr (2008) Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: results from the third National Health and Nutrition Examination Survey. Am J Epidemiol 168:577–586
Segal E, Zinnman H, Raz B et al (2004) Adherence to vitamin D supplementation in elderly patients after hip fracture. J Am Geriatr Soc 52:474–475
Seifried HE, McDonald SS, Anderson DE et al (2003) The antioxidant conundrum in cancer. Cancer Res 63:4295–4298
Sergeev IN (2005) Calcium signaling in cancer and vitamin D. J Steroid Biochem Mol Biol 97:145–151
Shigenga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91:10771–10778
Slater AF, Nobel CS, Orrenius S (1995) The role of intracellular oxidants in apoptosis. Biochim Biophys Acta 1271:59–62
Smith SM, Gardner KK, Locke J et al (2009) Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr 89:1092–1098
Steel GG (2002) Basic clinical radiobiology. Oxford University Press, London/New York
Stolzenberg-Solomon RZ (2009) Vitamin D and pancreatic cancer. Ann Epidemiol 19:89–95
Stolzenberg-Solomon RZ, Vieth R, Azad A et al (2006) A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res 66:10213–10219
Stumpf WE (2006) The dose makes the medicine. Drug Discov Today 11:550–555
Stumpf WE, O’Brien LP (1987) 1, 25(OH)2 vitamin D3 sites of action in the brain. An autographic study. Histochemistry 87:393–406
Swerdlow S, Distelhorst CW (2007) Bcl-2 regulated calcium signals as common mediators of both apoptosis and autophagy. Dev Cell 12:178–179
Tan CY, Statham B, Marks R et al (1982) Skin thickness measurements by pulsed ultrasound: its reproducibility, validation, and variability. Br J Dermatol 106:657–666
Tavera-Mendoza L, Wang T-T, Lallemant B et al (2006) Convergence of vitamin D and retinoic acid signaling at a common response element. EMBO Rep 7:180–185
Tetich M, Leskiewicz M, Budziszewska B et al (2003) The third multidisciplinary conference on drug research, Pila 2002. Effects of 1alpha,25-dihydroxyvitamin D3 and some putative steroid neuroprotective agents on the hydrogen peroxide-induced damage in neuroblastoma-glioma hybrid NG108-15. Acta Pol Pharm 60:351–355
Tombal B, Denmeade SR, Gillis J-M et al (2002) A supramicromolar elevation of intracellular free calcium ([Ca2+]i) is consistently required to induce the execution phase of apoptosis. Cell Death Differ 9:561–573
Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534
Tuohimaa P, Tenkanen L, Ahonen M et al (2004) Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer 108:104–108
Utiger RD (1998) The need for more vitamin D. N Engl J Med 338:828–829
van den Bemd G-JCM, Pols HAP, van Leeuwen JPTM (2000) Anti-tumor effects of 1, 25-dihydroxyvitamin D3 and vitamin D analogs. Curr Pharm Des 6:717–732
van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyviatmin D3: basic concepts. J Steroid Biochem Biol 97:93–101
Vieth R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 69:842–856
Vieth R, Kimball S (2006) Vitamin D in congestive heart failure. Am J Clin Nutr 83:731–732
Walters MR (1992) Newly identified actions of the vitamin D endocrine system. Endocr Rev 13:719–764
Wang JY, Wu JN, Cherng TL et al (2001) Vitamin D3 attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res 904:67–75
Wang T-T, Tavera-Mendoza LE, Laperriere D et al (2005) Large-scale in silico and microarray-based identification of direct 1, 25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19:2685–2695
Wang TJ, Pencina MJ, Booth SL et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511
Warner HR (1999) Apoptosis: a two-edged sword in aging. Ann N Y Acad Sci 887:1–11
Warner HR, Hodes RJ, Pocinki K (1997) What does cell death have to do with aging? J Am Geriatr Soc 45:1140–1146
Wicherts IS, van Schoor NM, Boeke AJP et al (2007) Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metab 92:2058–2065
Willson RL (1992) Free radical-induced biological damage and the critical roles of vitamin A, vitamin C, vitamin D and vitamin E and of copper, iron, selenium and zinc. J Nutr Sci Vitaminol (Tokyo). S-19-2:541–544
Yamasaki H (1990) Gap junctional intercellular communication and carcinogenesis. Carcinogenesis 11:1051–1058
Yamasaki H, Naus CC (1996) Role of connexin genes in growth control. Carcinogenesis 17:1199–1213
Yetley EA (2008) Assessing the vitamin D status of the US population. Am J Clin Nutr 88:558S–564S
Ylikomi T, Laaksi I, Lou Y-R et al (2002) Antiproliferative action of vitamin D. Vitam Horm 64:357–406
Yue Z, Jin S, Yang C et al (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 100:15077–15082
Zittermann A, Schleithoff SS, Koerfer R (2005) Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 94:483–492
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Hayes, D.P. Vitamin D and ageing. Biogerontology 11, 1–16 (2010). https://doi.org/10.1007/s10522-009-9252-0
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DOI: https://doi.org/10.1007/s10522-009-9252-0