Genetics of longevity. Data from the studies on Sicilian centenarians

Immunity & Ageing

Giuseppina Colonna-Romano²  Domenico Lio²  Letizia Scola²  Loredana Vaccarino²  MariaValeria Pellicanò¹  Marisa Palmeri²  Adriana Martorana²  Florinda Listì²  Giusi I Forte²  Matteo Bulati²  Silvio Buffa²  Manuela Bova²  Giulia Accardi²  Giuseppina Candore²  Carmela R Balistreri² 

[1] Department of Internal Medicine II, Center for Medical Research, University of Tübingen, Tübingen Ageing and Tumor Immunology group, Waldhörnlestr. 22, Tübingen 72072, Germany;Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, Palermo 90134, Italy

关键词: Epigenomics;    Pro/anti-inflammatory polymorphisms;    Genetics;    Immune system;   

Others  :  817470
DOI  :  10.1186/1742-4933-9-8

 received in 2012-03-29, accepted in 2012-04-23,  发布年份 2012

【 摘 要 】

The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic changes in ageing and longevity.

【 授权许可】

   
2012 Balistreri et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Terry DF, Wilcox MA, McCormick MA, Pennington JY, Schoenhofen EA, Andersen SL, Perls TT: Lower all-cause, cardiovascular, and cancer mortality in centenarians' offspring. J Am Geriatr Soc 2004, 52:2074-2076.
• [2]Terry DF, McCormick M, Andersen S, Pennington J, Schoenhofen E, Palaima E, Bausero M, Ogawa K, Perls TT, Asea A: Cardiovascular disease delay in centenarian offspring: role of heat shock proteins. Ann N Y Acad Sci 2004, 1019:502-505.
• [3]Barzilai N, Gabriely I, Gabriely M, Iankowitz N, Sorkin JD: Offspring of centenarians have a favorable lipid profile. J Am Geriatr Soc 2001, 49:76-79.
• [4]Rose G, Passarino G, Scornaienchi V, Romeo G, Dato S, Bellizzi D, Mari V, Feraco E, Maletta R, Bruni A, Franceschi C, De Benedictis G: The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring. BMC Genomics 2007, 8:293. BioMed Central Full Text
• [5]Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A: Human immunosenescence: is it infectious? Immunol Rev 2005, 205:257-268.
• [6]Chidrawar S, Khan N, Wei W, McLarnon A, Smith N, Nayak L, Moss P: Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol 2009, 155:423-432.
• [7]Derhovanessian E, Larbi A, Pawelec G: Biomarkers of human immunosenescence: impact of Cytomegalovirus infection. Curr Opin Immunol 2009, 21:440-445.
• [8]Derhovanessian E, Maier AB, Beck R, Jahn G, Hähnel K, Slagboom PE, de Craen AJ, Westendorp RG, Pawelec G: Hallmark features of immunosenescence are absent in familial longevity. Immunol 2010, 185:4618-4624.
• [9]Colonna Romano G, Bulati M, Aquino A, Scialabba G, Candore G, Lio D, Motta M, Malaguarnera M, Caruso C: B cells in the aged: CD27, CD5 and CD40 expression. Mech Ageing Dev 2003, 124:389-393.
• [10]Colonna Romano G, Cossarizza A, Aquino A, Scialabba G, Bulati M, Lio D, Candore G, Di Lorenzo G, Fradà G, Caruso C: Age- and gender-related values of lymphocyte subsets in subjects from northern and southern Italy. Arch Gerontol Geriatr (Suppl) 2002, 8:99-107.
• [11]Listì F, Candore G, Modica MA, Russo MA, Di Lorenzo G, Esposito-Pellitteri M, Colonna Romano G, Aquino A, Bulati M, Lio D, Franceschi C, Caruso C: A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence. Ann N Y Acad Sci 2006, 1089:487-495.
• [12]Candore G, Di Lorenzo G, Mansueto P, Melluso M, Fradà G, Li Vecchi M, Esposito Pellitteri M, Drago A, Di Salvo A, Caruso C: Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians. Mech Ageing Dev 1997, 94:183-190.
• [13]Colonna-Romano G, Bulati M, Aquino A, Vitello S, Lio D, Candore G, Caruso C: B cell immunosenescence in the elderly and in centenarians. Rejuvenation Res 2008, 11:433-439.
• [14]Colonna-Romano G, Bulati M, Aquino A, Pellicanò M, Vitello S, Lio D, Candore G, Caruso C: A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev 2009, 130(10):681-690.
• [15]Bulati M, Buffa S, Candore G, Caruso C, Dunn-Walters DK, Pellicanò M, Wu YC, Colonna Romano G: B cells and immunosenescence: a focus on IgG+IgD-CD27- (DN) B cells in aged humans. Ageing Res Rev 2011, 10:274-284.
• [16]Buffa S, Bulati M, Pellicanò M, Dunn-Walters DK, Wu YC, Candore G, Vitello S, Caruso C, Colonna-Romano G: B cell immunosenescence: different features of naive and memory B cells in elderly. Biogerontology 2011, 12:473-483.
• [17]Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, Lee EH, Milner EC, Sanz I: A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol 2007, 178:6624-6633.
• [18]Sanz I, Wei C, Lee FE, Anolik J: Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol 2008, 20(1):67-82.
• [19]Cagigi A, Du L, Dang LV, Grutzmeier S, Atlas A, Chiodi F, Pan-Hammarström Q, Nilsson A: CD27(-) B-cells produce class switched and somatically hyper-mutated antibodies during chronic HIV-1 infection. PLoS One 2009, 4(5):e5427.
• [20]Colonna-Romano G, Buffa S, Bulati M, Candore G, Lio D, Pellicanò M, Vasto S, Caruso C: B cells compartment in centenarian offspring and old people. Curr Pharm Des 2010, 16:604-608.
• [21]Frasca D, Riley RL, Blomberg BB: Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans. Semin Immunol 2005, 17(5):378-384.
• [22]Dunn-Walters DK, Ademokun AA: B cell repertoire and ageing. Curr Opin Immunol 2010, 22(4):514-520.
• [23]Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB: B cells and aging: molecules and mechanisms. Trends Immunol 2009, 30(7):313-318.
• [24]Kumar R, Burns EA: Age-related decline in immunity: implications for vaccine responsiveness. Expert Rev Vaccines 2008, 7(4):467-479.
• [25]Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E, Nilsson BO, Wikby A, Kipling D, Dunn-Walters DK: B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell 2009, 8(1):18-25.
• [26]Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R: Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 2009, 21(3):201-209.
• [27]Perrig-Chiello P, Hutchison S: Health and well-being in old age: the pertinence of a gender mainstreaming approach in research. Gerontology 2010, 56:208-213.
• [28]May RC: Gender, immunity and the regulation of longevity. Bioessays 2007, 29(8):795-802.
• [29][http://www.istat.it] webcite
• [30]Candore G, Balistreri CR, Colonna-Romano G, Lio D, Listì F, Vasto S, Caruso C: Gender-related immune-inflammatory factors, age-related diseases, and longevity. Rejuvenation Res 2010, 13:292-729.
• [31]Candore G, Balistreri CR, Listì F, Grimaldi MP, Vasto S, Colonna-Romano G, Franceschi C, Lio D, Caselli G, Caruso C: Immunogenetics, gender, and longevity. Ann N Y Acad Sci 2006, 1089:516-537.
• [32]Capri M, Salvioli S, Monti D, Caruso C, Candore G, Vasto S, Olivieri F, Marchegiani F, Sansoni P, Baggio G, Mari D, Passarino G, De Benedictis G, Franceschi C: Human longevity within an evolutionary perspective: The peculiar paradigm of a post-reproductive genetics. Exp Gerontol 2008, 43:53-60.
• [33]Lio D, Balistreri CR, Colonna-Romano G, Motta M, Franceschi C, Malaguarnera M, Candore G, Caruso C: Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population. Genes Immun 2002, 3:20-24.
• [34]Beutler E: Iron storage disease: facts, fiction and progress. Blood Cells Mol Dis 2007, 39:140-147.
• [35]Pietrangelo A: Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 2010, 139:393-408. 408.e1-2
• [36]Franceschi C, Motta L, Motta M, Malaguarnera M, Capri M, Vasto S, Candore G, Caruso C: IMUSCE. The extreme longevity: the state of the art in Italy. Exp Gerontol 2008, 43:45-52.
• [37]Troen BR: The biology of aging. Mt Sinai J Med 2003, 70:3-22.
• [38]Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, Monti D, Franceschi C: Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation 2008, 15:224-240.
• [39]Candore G, Colonna-Romano G, Balistreri CR, Di Carlo D, Grimaldi MP, Listì F, Nuzzo D, Vasto S, Lio D, Caruso C: Biology of longevity: role of the innate immune system. Rejuvenation Res 2006, 9:143-148.
• [40]Williams GC: Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957, 398-411. 11
• [41]Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C: Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 2007, 128:83-91.
• [42]Balistreri CR, Colonna-Romano G, Lio D, Candore G, Caruso C: TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases. J Clin Immunol 2009, 29:406-415.
• [43]Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, Frees K, Watt JL, Schwartz DA: TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000, 25:187-191.
• [44]Ferwerda B, McCall MB, Alonso S, Giamarellos-Bourboulis EJ, Mouktaroudi M, ùIzagirre N, Syafruddin D, Kibiki G, Cristea T, Hijmans A, Hamann L, Israel S, ElGhazali G, Troye-Blomberg M, Kumpf O, Maiga B, Dolo A, Doumbo O, Hermsen CC, Stalenhoef AF, van Crevel R, Brunner HG, Oh DY, Schumann RR, de la Rúa C, Sauerwein R, Kullberg BJ, van der Ven AJ, van der Meer JW, Netea MG: TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci USA 2007, 104:16645-16650.
• [45]Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW, Netea MG: Functional consequences of toll-like receptor 4 polymorphisms. Mol Med 2008, 14:346-352.
• [46]Balistreri CR, Caruso C, Grimaldi MP, Listì F, Vasto S, Orlando V, Campagna AM, Lio D, Candore G: CCR5 receptor: biologic and genetic implications in age-related diseases. Ann NY Acad Sci 2007, 1100:162-172.
• [47]Listì F, Caruso M, Incalcaterra E, Hoffmann E, Caimi G, Balistreri CR, Vasto S, Scafidi V, Caruso C, Candore G: Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics. Curr Pharm Des 2008, 14:2678-2685.
• [48]Balistreri CR, Candore G, Caruso M, Incalcaterra E, Franceschi C, Caruso C: Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity. Haematologica 2008, 93:637-638.
• [49]Balistreri CR, Candore G, Colonna-Romano G, Lio D, Caruso M, Hoffmann E, Franceschi C, Caruso C: Role of Toll-like receptor 4 in acute myocardial infarction and longevity. JAMA 2004, 292:2339-2340.
• [50]Perls T, Terry D: Genetics of exceptional longevity. Exp Gerontol 2003, 38:725-730.
• [51]Candore G, Balistreri CR, Grimaldi MP, Listì F, Vasto S, Caruso M, Caimi G, Hoffmann E, Colonna-Romano G, Lio D, Paolisso G, Franceschi C, Caruso C: Opposite role of pro-inflammatory alleles in acute myocardial infarction and longevity: results of studies performed in a Sicilian population. Ann NY Acad Sci 2006, 1067:270-275.
• [52]Incalcaterra E, Caruso M, Balistreri CR, Candore G, Lo Presti R, Hoffmann E, Caimi G: Role of genetic polymorphisms in myocardial infarction at young age. Clin Hemorheol Microcirc 2010, 46:291-298.
• [53]Balistreri CR, Carruba G, Calabrò M, Campisi I, Di Carlo D, Lio D, Colonna-Romano G, Candore G, Caruso C: CCR5 proinflammatory allele in prostate cancer risk: a pilot study in patients and centenarians from Sicily. Ann NY Acad Sci 2009, 1155:289-292.
• [54]Balistreri CR, Caruso C, Carruba G, Miceli V, Campisi I, Listì F, Lio D, Colonna-Romano G, Candore G: A pilot study on prostate cancer risk and pro-inflammatory genotypes: pathophysiology and therapeutic implications. Curr Pharm Des 2010, 16:718-724.
• [55]Balistreri CR, Candore G, Lio D, Colonna-Romano G, Di Lorenzo G, Mansueto P, Rini G, Mansueto S, Cillari E, Franceschi C, Caruso C: Role of TLR4 receptor polymorphisms in Boutonneuse fever. Int J Immunopathol Pharmacol 2005, 18:655-660.
• [56]Balistreri CR, Caruso C, Listì F, Colonna-Romano G, Lio D, Candore G: LPS-mediated production of pro/anti-inflammatory cytokines and eicosanoids in whole blood samples: biological effects of +896A/G TLR4 polymorphism in a Sicilian population of healthy subjects. Mech Ageing Dev 2011, 132:86-92.
• [57]Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA: Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol 2009, 9:447-453.
• [58]Iannitti T, Palmieri B: Inflammation and genetics: an insight in the centenarian model. Hum Biol 2011, 83:531-559.
• [59]Caruso C, Candore G, Colonna-Romano G, Lio D, Franceschi C: Inflammation and life-span. Science. 2005, 307:208-209.
• [60]Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C: Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun 2002, 3:30-33.
• [61]Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafé M, Cavallone L, Marchegiani F, Olivieri F, Franceschi C, Caruso C: Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10-1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP. J Med Genet 2003, 40:296-299.
• [62]Lio D, Candore G, Crivello A, Scola L, Colonna-Romano G, Cavallone L, Hoffmann E, Caruso M, Licastro F, Caldarera CM, Branzi A, Franceschi C, Caruso C: Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease. J Med Genet 2004, 41:790-794.
• [63]Lio D, Scola L, Crivello A, Bonafè M, Franceschi C, Olivieri F, Colonna-Romano G, Candore G, Caruso C: Allele frequencies of +874 T- > A single nucleotide polymorphism at the first intron of interferon-gamma gene in a group of Italian centenarians. Exp Gerontol 2002, 37:315-319.
• [64]Palmeri M, Misiano G, Malaguarnera M, Forte GI, Vaccarino L, Milano S, Scola L, Caruso C, Motta M, Maugeri D, Lio D: Cytokine serum profile in a group of sicilian nonagenarians. J Immunoassay Immunochem 2012, 33:82-90.
• [65]Park LK, Friso S, Choi SW: Nutritional influences on epigenetics and age-related disease. Proc Nutr Soc 2012, 71:75-83.
• [66]Portela A, Esteller M: Epigenetic modifications and human disease. Nat Biotechnol 2010, 28:1057-1068.
• [67]Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, Jinno Y: Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 2005, 69(Pt 1):134.
• [68]Wu C, Morris JR: Genes, genetics, and epigenetics: a correspondence. Science 2001, 293:1103-1105.
• [69]Antequera F, Bird A: CpG islands. EXS. 1993, 64:169-185.
• [70]Decottignies A, d'Adda di Fagagna F: Epigenetic alterations associated with cellular senescence: a barrier against tumorigenesis or a red carpet for cancer? Semin Cancer Biol 2011, 21:360-366.
• [71]Lim U, Song MA: Dietary and lifestyle factors of DNA methylation. Methods Mol Biol 2012, 863:359-376.
• [72]Choi SW, Friso S: Epigenetics: A New Bridge between Nutrition and Health. Adv Nutr 2010, 1:8-16.
• [73]Vasto S, Scapagnini G, Rizzo C, Monastero R, Marchese A, Caruso C: Mediterranean diet and longevity in Sicily: a survey in Sicani Mountains Population. Rejuvenation Res, in press.
• [74]Mitić T, Emanueli C: Diabetes-induced epigenetic signature in vascular cells. Endocr Metab Immune Disord Drug Targets 2012.
• [75]Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F, Mullen Y, Pfeifer GP, Ferreri K: Insulin gene expression is regulated by DNA methylation. PLoS One 2009, 4:10.
• [76]Zhao J, Goldberg J, Bremner JD, Vaccarino V: Global DNA methylation is associated with insulin resistance: a monozygotic twin study. Diabetes 2012, 61:542-546.