Abstract
The pivotal role played by zinc–gene interaction in affecting the inflammatory response mediated by IL-6 in ageing, successful ageing (nonagenarians) and the most common age-related diseases is now recognized. Contradictory data emerging from association studies of IL-6 polymorphisms with longevity and chronic age-related diseases seem to arise from the interaction of this inflammatory pathway with dietary habits. Similar conclusions are expected to arise from association studies with the frailty syndrome. Some polymorphisms of genes related to vitamin B12 availability have been already found to be associated with frailty suggesting a possible link among diet–gene interaction and frailty in old age. Other studies in this field are urgently required because of their high potential for suggesting strategies in the care and prevention of frailty in ageing through dietary interventions, in which nutrient zinc may play a pivotal role taking into account that the high copper to zinc ratio is a significant index of the mortality in older people.
Similar content being viewed by others
Abbreviations
- MTHFR:
-
Methylenetetrahydrofolate reductase
- MTR:
-
Methionine synthase
- MTRR:
-
Methionine synthase reductase
- TCN2:
-
Transcobalamin II
- MMA:
-
Methylmalonic acid
- MT:
-
Metallothioneins
- IL-6:
-
Interleukin-6
- IGF-1:
-
Insulin-like Growth Factor-1
- PON1:
-
Paraoxonase 1
- LPS:
-
Lipopolysaccharide
References
Baik HW, Russell RM (1999) Vitamin B12 deficiency in the elderly. Annu Rev Nutr 19:357–377
Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 31:2357–2361
Darnton-Hill I, Margetts B, Deckelbaum R (2004) Public health nutrition and genetics: implications for nutrition policy and promotion. Proc Nutr Soc 63:173–185
Di Bona D, Vasto S, Capurso C, Christiansen L, Deiana L, Franceschi C, Hurme M, Mocchegiani E, Rea M, Lio D, Candore G, Caruso C (2009) Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res Rev 8:36–42
Dreosti IE (2001) Zinc and the gene. Mutat Res 475:161–167
Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23:2375–2378
Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47:639–646
Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 126:351–361
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105
Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 59:255–263
Giacconi R, Cipriano C, Albanese F, Boccoli G, Saba V, Olivieri F, Franceschi C, Mocchegiani E (2004) The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing. Exp Gerontol 39:621–628
Kapadia C (2000) Cobalamin (Vitamin B12) deficiency: is it a problem for our aging population and is the problem compounded by drugs that inhibit gastric acid secretion? J Clin Gastroenterol 30:4–6
Kirkwood TB (2002) Evolution of ageing. Mech Ageing Dev 123:737–745
Kuningas M, Mooijaart SP, van Heemst D, Zwaan BJ, Slagboom PE, Westendorp RG (2008) Genes encoding longevity: from model organisms to humans. Aging Cell 7:270–280
Leng SX, Xue QL, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871
Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Mohlke KL, Ibrahim JG, Thomas NE, Sharpless NE (2009) INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLOS One 4:e5027
Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61:575–584
Malavolta M, Giacconi R, Piacenza F, Santarelli L, Cipriano C, Costarelli L, Tesei S, Pierpaoli S, Basso A, Galeazzi R, Lattanzio F, Mocchegiani E (2009) Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology. doi:10.1007/s10522-009-9251-1
Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, Chakravarti A, Stabler SP, Fallin MD (2010) Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty. J Nutr Health Aging 14:73–77
Mattson MP (2008) Dietary factors, hormesis and health. Ageing Res Rev 7:43–48
Mazzatti DJ, Malavolta M, White AJ, Costarelli L, Giacconi R, Muti E, Cipriano C, Powell JR, Mocchegiani E (2008) Effects of interleukin-6 −174C/G and metallothionein 1A +647A/C single-nucleotide polymorphisms on zinc-regulated gene expression in ageing. Exp Gerontol 43:423–432
Mitnitski AB, Graham JE, Mogilner AJ, Rockwood K (2002) The mortality rate as a function of accumulated deficits in a frailty index. Mech Ageing Dev 123:1457–1460
Mitrou PN, Kipnis V, Thiébaut AC, Reedy J, Subar AF, Wirfält E, Flood A, Mouw T, Hollenbeck AR, Leitzmann MF, Schatzkin A (2007) Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study. Arch Intern Med 167:2461–2468
Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Tesei S, Malavolta M (2006) Nutrient-gene interaction in ageing and successful ageing. A single nutrient (zinc) and some target genes related to inflammatory/immune response. Mech Ageing Dev 127:517–525
Mocchegiani E, Giacconi R, Costarelli L, Muti E, Cipriano C, Tesei S, Pierpaoli S, Giuli C, Papa R, Marcellini F, Gasparini N, Pierandrei R, Piacenza F, Mariani E, Monti D, Dedoussis G, Kanoni S, Herbein G, Fulop T, Rink L, Jajte J, Malavolta M (2008) Zinc deficiency and IL-6 −174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study. Exp Gerontol 43:433–444
Olivieri F, Bonafe M, Cavallone L, Giovanetti S, Marchegiani F, Cardelli M, Mugianesi E, Giampieri C, Moresi R, Stecconi R, Lisa R, Franceschi C (2002) The −174C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol 37:309–314
Qu T, Walston JD, Yang N, Fedarko NS, Xue QL, Beamer BA, Ferrucci L, Rose NR, Leng SX (2009) Upregulated ex vivo expression of stress-responsive inflammatory pathway genes by LPS-challenged CD14+ monocytes in frail older adults. Mech Ageing Dev 130:161–166
Rea IM, Ross OA, Armstrong M, McNerlan S, Alexander DH, Curran MD, Middleton D (2003) Interleukin-6-gene C/G 174 polymorphism in nonagenarian and octogenarian subjects in the BELFAST study. Reciprocal effects on IL-6, soluble IL-6 receptor and for IL-10 in serum and monocyte supernatants. Mech Ageing Dev 124:555–561
Stover PJ (2006) Influence of human genetic variation on nutritional requirements. Am J Clin Nutr 83:436S–442S
Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144
Wang XY, Hurme M, Jylha M, Hervonen A (2001) Lack of association between human longevity and polymorphisms of IL-1 cluster, IL-6, IL-10 and TNF-alpha genes in Finnish nonagenarians. Mech Ageing Dev 123:29–38
Acknowledgment
Supported by INRCA, CARILORETO and CARIVERONA.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mocchegiani, E., Basso, A., Giacconi, R. et al. Diet (zinc)–gene interaction related to inflammatory/immune response in ageing: possible link with frailty syndrome?. Biogerontology 11, 589–595 (2010). https://doi.org/10.1007/s10522-010-9276-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-010-9276-5