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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 of the present study are limited in their statistical power and thus we cannot make definitive conclusions. Only longitudinal studies specifically designed for addressing the impact of the IL-6 2174 G/C promoter polymorphism on extreme longevity could provide more robust evidence for further understanding the role of this polymorphisms in the reaching of 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 skilful assistance.

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