Panza, F., Capurso, C., D'Amelio, A., Gaddi, A., Daddato, S., Galletti, C., Trabucchi, M., Boffelli, S., Rozzini, R., Motta, L., Rapisarda, R., Receputo, G., Mattace, R., Motta, M., Pansini, L., Masotti, G., Marchionni, N., Petruzzi, E., Bertolini, S., Agretti, M., Costelli, P., Mari, D., Duca, F.A.F.D.E.L.I.O.A.D.I.A.N.O.E.G.A.B.L.IDavignon, J., Gregg, R.E., Sing, C.F., Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis, Ershler, W.B., Keller, E.T., Age-associated increased interleukin gene expression, late-life diseases, and frailty. Annu. Rev. Med., Fagiolo, U., Cossarizza, A., Scala, E., Fanales-Belasio, E., Ortolani, C., Cozzi, E., Monti, D., Franceschi, C., Paganelli, R., Increased cytokine production in mononuclear cells of healthy elderly people. Eur. J. Immunol., Ferrucci, L., Harris, T.B., Guralnik, J.M., Tracy, R.P., Corti, M.C., Cohen, H.J., Penninx, B., Pahor, M., Wallace, R., Havlik, R.J., Serum IL-6 level and the development of disability in older persons. J. Am. Geriatr. Soc., Flex, A., Gaetani, E., Pola, R., Santoliquido, A., Aloi, F., Papaleo, P., Dal Lago, A., Pola, E., Serricchio, M., Tondi, P., Pola,P . , The G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease. Eur. J. Vasc. Endovasc. Surg . , Fishman,D . , Faulds,G . , Jeffery,R . , Mohamed-Ali,V . , Yudkin,J.S . , Humphries,S . , Woo,P . , The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest., Frisoni, G.B., Louhija, J., Geroldi, C., Trabucchi, M., Longevity and the epsilon allele of apolipoprotein E: the Finnish Centenarians Study. J. Gerontol. A Biol. Sci. Med. Sci., Harris, T.B., Ferrucci, L., Tracy, R.P., Corti, M.C., Wacholder, S., Ettinger, W.H. Jr., Heimovitz, H., Cohen,H.J . , Wallace,R . , Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am. J. Med., Jones,K.G . , Brull,D.J . , Brown,L.C . , Sian,M . , Greenhalgh,R.M . , Humphries,S.E . , Powell,J.T . , Interleukin-6 (IL-6) and the While it appears that APOE may play a role in longevity (Schachter et al., 1994; Louhija et al., 1994; Panza et al., 1999; Frisoni et al., 2001), the current evidence in conjunction with previous works with contrasting findings (Bonafe et al., 2001; Wang et al., 2001; Rea et al., 2003) does not support a similar involvement for the IL-6 2174 G/C promoter gene, nor of an interaction between the alleles of both genes. However, this study has some potential limitations. In fact, we must also acknowledge that the cross-sectional design and a relatively small number of centenarians in the present study limit their statistical power and we cannot make definitive conclusions. Only longitudinal studies designed specifically to address the impact of the IL-6 2174 G/C promoter polymorphism on extreme longevity could provide more robust evidence to further understand the role of this polymorphism in reaching human extreme longevity. Acknowledgements This study was supported by Italian Longitudinal Study on Aging (ILSA) (Italian National Research Council-CNR- Targeted Project on Aging-Grants 9400419PF40 and 95973PF40), and by AFORIGE (Associazione per la Formazione e la Ricerca in Geriatria). CC, AMC, and FP were supported by a PhD grant in Carcinogenesis, Aging, and Immunoregulation from the European Union. The authors wish to thank Dr Giovanni Castellaneta, Dr Amalia Terralavoro, Pfizer Inc., Dr Massimo Ulivi, TIBMOL BIOL Inc., and Giuseppe Giorgio for their skilful assistance. References Baggio,G . , Donazzan,S . , Monti,D . , Mari,D . , Martini,S . , Gabelli,Dalla Vestra,M . , Previato,L . , GuidGoldgaber, D., Roses, A.D., "Association of apolipoprotein E allele e with late-onset familial and sporadic Alzheimer's disease." Neurology, 

Schachter, F., Faure-Delanef, L., Guenot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., Cohen, D., "Genetic associations with human longevity at the APOE and ACE loci." Nat. Genet., 

Solfrizzi, V., Panza, F., Torres, F., Mastroianni, F., Del Parigi, A., Venezia, A., Capurso, A., "High monounsaturated fatty acids intake protects against age-related cognitive decline." Neurology,

Terry, C.F., Loukaci, V., Green, F.R., "Cooperative influence of genetic polymorphisms on interleukin transcriptional regulation." J. Biol. Chem., 

Wang, X.Y., Hurme, M., Jylha, M., Hervonen, A., "Lack of association between human longevity and polymorphisms of IL-cluster, IL-, IL-, and TNF-alpha genes in Finnish nonagenarians." Mech. Ageing Dev.