2. Materials and methods

Genomic DNA samples for this study were obtained through AKEA (the name AKEA is derived from an expression in the Sardinian language that means health and life for 100 years!) study of Sardinian centenarians (Deiana et al.). At the time of the present study, DNA samples for HFE typing were available from 57 centenarians (age range from 100 to 105; 17 men and 40 women) and from 60 controls (60G.M., Carru, C., Delitala, G., A., Mariotti, S., Nieddu, A., Pettinato, S., Putzu, P., C., Baggio, G., AKEnn os. The Sardinia Study of Longevity. Aging Clin. Exp. Res., (year not provided) / Feder, J.N., Gnirke, A., Thomas, W., et al., A novel MHC I-like gene is mutated in patients with hereditary hemochromatosis. Nat. Genet., (year not provided) / Klein, J., Sato, A., The HLA system. Second of two parts. N. Engl. J. Med., (year not provided) / Lio, D., Balistreri, C.R., Colonna-Romano, G., Motta, M., Ceschi, C., Malaguarnera, M., Candore, G., Caruso, C., Association between the MHC class I gene HFE and longevity: a study in the Sicilian population. Genes Immunity (year not provided) / Lucotte, G., Frequency analysis and allele map in favor of Celtic origin of the CY mutation of hemochromatosis. Cells Mol. Dis. (year not provided) / Merryweather-Clarke, A.T., Pointon, J.J., Shearman, J.D., K.J.H., Global prevalence of putative mutations. J. Med. Genet.(year not provided) / Mura, C., Raguenes, O., Ferec, C., HFE mutations analysis in hemochromatosis probands evidence for SC implication mild form of hemochromatosis. Blood (year not provided) / Oppenheimer, S.J., Iron and its relation to immunity and infectious disease. J. Nutr., (year not provided) / A theory is also a possible explanation for the apparent discrepancy with a recent study performed in Denmark. In a C282Y mutation high-carrier frequency population such as Denmark (Lucotte 2001; Bathum et al., 2001), this mutation shows an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy. The observed reduction in C282Y mutation carrier frequency persists until age 95 years; however, the frequency in the centenarian group was the same as that in the youngest group for both men and women (Bathum et al., 2001). So, in that study, heterozygosity for C282Y has a higher mortality rate in the younger groups but becomes beneficial in the oldest old. All together present and previous reports seem to strongly suggest that longevity is the result of interaction between genetic and environmental factors that, in different age, gender, and population, may result in successful or unsuccessful aging. Acknowledgements The authors are grateful to Dr. Alessandra Errigo for help in patient recruitment and blood sample processing. The AKEA Project coordinated by Professor L. Deiana was funded by grants from the Regione Autonoma della Sardegna and MIUR (ex 40% and ex 60%). The Gruppo di Studio sull'immunosenescenza coordinated by Professor C. Caruso was funded by grants from MIUR, Rome (ex 40%, to CC and DL; ex 60% to GC and GCR). The collaboration between this group and the Istituto Nazionale di Riposo e Cura per Anziani was enhanced by a cooperation contract (Longevity and elderly disability biological markers) and by the EU thematic network program ImAginE (QLK6-CT-1999-02031). References Andrews, N.C., 1999. Disorders of iron metabolism. N. Engl. J. Med. 341(26), 1986-1995. C.R., Candore, G., Almasio, P., Colonna Romano, G., Craxi, A., Motta, M., Piazza, G., Malaguarnera, M., Lio, D., Caruso, C., Analysis of HFE gene mutations in the Sicilian Population: implications for survival and longevity, Arch. Gerontol. Geriatr., (year not provided) / Shorter, E., 1982. A History of Women's Bodies. Basic Books, Inc, New York. Rendine, S., Borelli, I., Barbanti, M., Sacchi, N., Roggero, S., Curtoni, E.S., 1998. HLA polymorphisms in Italian bone marrow donors: a regional analysis. Tissue Antigens (year not provided) / Rochette, J., Pointon, J., Fisher, J., et