dinians. Several possibilities may explain this discrepancy. The original Italian findings may be chance effects. However, IL-6 data (8) have been confirmed in the Irish population (15, 16). In a recent Irish study, a non-signif- icant trend for a reduced frequency of the GG polymor- phism of IL-6 in octo/nonagenarians from the BELFAST study group compared with younger subjects of the local population was reported. This trend was more marked in elderly males than in females (15). In another study per- formed on aged Irish people, an overall decrease in the –174GG in the total aged cohort, with particular re- spect to total males in comparison with controls during the study, appeared to concur with Italian findings (16). So, in studies carried out to date, IL-6 looks like the most in- teresting cytokine with respect to longevity, since in three studies, in separate Caucasian European elderly populations and with different selection criteria, appear to demonstrate a decrease in IL-6 –174GG homozygote fre- quency with extreme old age. The frequency of the anti- inflammatory high-producer polymorphism cytokine of IL- 10, which was also apparently increased in Italian cen- tenarian men (9), was not increased in separate studies on other Caucasoid nonagenarians or in male subjects ana- lyzed separately (14, 15). However, the results were confirmed in a further study performed in South Italy (10), and in the Italian population, the reciprocal anti-inflam- matory low-producer polymorphism is associated with un- successful aging (37, 40). Lastly, the IFN-γ, high-pro- ducer combination haplotype 12CA/+847T showed a de- crease in centenarian Italian women (11), with a trend to-

ACKNOWLEDGEMENTS

The authors are grateful to A. Errigo, MD, for help in subject re- cruitment and blood sample processing. The “AKEA project” coordi- nated by Prof. L. Deiana was funded by grants from the Regione Au- tonoma della Sardegna and the Italian Ministry of Education, Univer- sity and Research (MIUR) (ex 40% and ex 60%). The “Gruppo di Stu- dio sull’Immunosenescenza”, coordinated by Prof. C. Caruso, was funded by grants from MIUR (ex 40%, to CC and DL; ex 60% to CC, DL, GC and GCR) and from the Ministry of Health projects “Parametri immunologici età-correlati” and “Studio multicentrico sui determi- nanti genetici e non genetici di salute nell'età avanzata”. Collaboration between this group and the Istituto Nazionale di Riposo e Cura per Anziani (INRCA) was enhanced by a cooperation contract (“Longevi- ty and elderly disability biological markers”) and by the EU thematic net- work program ImAginE (QLK6-CT-1999-02031).

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