Statistical methods: Allele and genotype frequencies for single SNPs were calculated and tested for departure from Hardy-Weinberg equilibrium using the χ2 test. Differences in allele and genotype distribution between cases (centenarians) and controls (younger population) were analyzed using logistic regression adjusted for non-genetic covariates under various genetic models that were defined as 1 (aa/Aa) versus 0 (AA) for dominant, 1 (aa) versus 0 (AA/Aa) for recessive, and 0 (AA) versus 1 (Aa) versus 2 (aa) for additive (A: major allele; a: minor allele). A Bonferroni step-down method was used for multiple comparison correction in allele association tests (63). Linkage disequilibrium and haplotype blocks (D′ > 0.90) were defined and visualized by the solid spine of LD method using Haploview 4.0 (http://www.broad.mit.edu/haploview/haploview). The haplotypes with frequency >5%.

Westendorp, R.G. and Slagboom, P.E. (1998) Chromosome 9q and human longevity: novel data and a meta-analysis of association studies. J. Gerontol. A Biol. Sci. Med. Sci., 53, B358–B363.

Novelli, V., Viviani Anselmi, C., Roncarati, R., Guffanti, G., Malovini, A., Piluso, G. and Puca, A.A. (2008) Lack of replication of genetic associations with human longevity. Biogerontology, 9, 85–92.

Lunetta, K.L., D'Agostino, R.B. Sr, Karasik, D., Benjamin, E.J., Guo, C.Y., Govindaraju, R., Kiel, D.P., Kelly-Hayes, M., Massaro, J.M., Pencina, M.J. et al. (2007) Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med. Genet., 8 Suppl 1, S13.

Willcox, B.J., Donlon, T.A., He, Q., Chen, R., Grove, J.S., Yano, K., Masaki, K.H., Willcox, D.C., Rodriguez, B. and Curb, J.D. (2008) FOXO3A genotype is strongly associated with human longevity. Proc. Natl Acad. Sci. USA, 105, 13987–13992.

Flachsbart, F., Caliebe, A., Kleindorp,R . , Blanche,H . , von Eller-Eberstein,H . , Nikolaus,S . , Schreiber,S . and Nebel,A . (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc. Natl Acad. Sci. USA, 106, 2700–2705.

Anselmi, C.V., Malovini, A., Roncarati, R., Novelli, V., Villa, F., Condorelli, G., Bellazzi, R. and Puca, A.A. (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res., 12, 95–104.

Cao, Y., Kamioka, Y., Yokoi, N., Kobayashi, T., Hino, O., Onodera, M., Mochizuki, N. and Nakae, J. (2008) Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. J. Biol. Chem., 283, 29660–29671.