As far as the functional implications of –174 locus, carri- ers of the G allele at –174 locus appear to be prone to develop lipid abnormalities and have a worse glucose handling capacity, a higher blood glycosylated hemoglo-

Bethin, K. E., Vogt, S.K. and Muglia, L.J., Interleukin-

is essential, corticotropin-releasing hormone-independent tor of the adrenal axis during immune system activation. Natl. Acad. Sci. USA.

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Xing, Z., Gauldie, J., Cox, G., Baumann, H. Jordana, M., X-F. and Achong, M. K., IL-

is an antiinflammatory required for controlling local or systemic acute responses. J. Clin. Invest.

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Mysliwska, J., Bryl, E., Foerster, J. and Mysliwski, A., of interleukin

and decrease of interleukin

production the ageing process are influenced by the health status. Ageing Dev.

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Young, D. G., Skibinski, G., Mason, J. I. and James, K., influence of age and gender on serum sulfate (DHEA-S), IL-

, IL-

soluble receptor (IL-

) and forming growth factor beta

(TGF-beta

) levels in normal blood donors. Clin. Exp. Immunol.

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Ferrucci, L., Harris, T. B., Guralnik, J. M., Tracy, R. P., Corti, C., Cohen, H. J., Penninx, B., Pahor, M., Wallace, R. and lik, R. J., Serum IL-

level and the development of disability older persons. J. Am. Geriatr. Soc.

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Harris, T. B., Ferrucci, L., Tracy, R. P., Corti, M. C., S., Ettinger, W. H. Jr, Heimovitz, H., Cohen, H. J. and R., Associations of elevated interleukin-

and C-reactive levels with mortality in the elderly. Am. J. Med.

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Kado, S., Nagase, T. and Nagata, N., Circulating levels interleukin-

, its soluble receptor and receptor complexes in patients with type

diabetes Acta. Diabetol.

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Ross, R., Atherosclerosis–an inflammatory disease. N. Engl. Med.

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Fishman, D., Faulds, G., Jeffery, R., Mohamed-Ali, V., J. S., Humphries, S. and Woo, P., The effect of novel phisms in the interleukin-

(IL-

) gene on IL-

transcription plasma IL-

levels, and an association with systemic-onset nile chronic arthritis. J. Clin. Invest.

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Terry, C. F., Loukaci, V. and Green, F. R., Cooperative of genetic polymorphisms on interleukin

transcriptional tion. J. Biol. Chem.

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Franceschi, C., Motta, L., Valensin, S., Rapisarda, R., zone, A., Berardelli, M., Motta, M., Monti, D., Bonafe`, M., rucci, L., Deiana, L., Pes, G.M., Carru, C., Desole, M.S., C., Sartoni, G., Gemelli, C., Lescai, F., Olivieri, F., F., Cardelli, M., Cavallone, L., Gueresi, P., Cossarizza, A., ano, L., Pini, G., Sansoni, P., Passeri, G., Lisa, R., fumo, L., Amadio, L., Giunta, S., Stecconi, R., Morresi, Viticchi, C., Mattace, R., De Benedictis, G. and Baggio, G., men and women follow different trajectories to reach longevity? Italian Multicenter Study on Centenarians. (Milano)

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Bruunsgaard, H., Pedersen, A. N., Schroll, M., Skinhoj, P. Pedersen, B. K., Impaired production of proinflammatory kines in response to lipopolysaccharide (LPS) stimulation elderly humans. Clin. Exp. Immunol

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De Benedictis, G., Rose, G., Carrieri, G., De Luca, M., cone, E., Passarino, G., Bonafe`, M., Monti, D., Baggio, Bertolini, S., Mari, D., Mattace, R. and Franceschi, C., chondrial DNA inherited variants are associated with aging and longevity in humans. FASEB J.

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De Benedictis, G., Carotenuto, L., Carrieri, G., De Luca, Falcone, E., Rose, G., Cavalcanti, S., Corsonello, F., E., Baggio, G., Bertolini, S., Mari, D., Mattace, R., Yashin, Bonafe`, M. and Franceschi, C., Gene/longevity

females), and a group of 70 centenarians (age range 100–110, median age = 101, 18 men and 52 women). No acute pathological condition was present in the subjects at the time of blood collection. All the subjects gave their informed consent.

4.2 Genotyping

DNA was extracted from blood lymphocytes by phenol chlo- roform according to standard procedures. Amplification of the –174 C/G locus was performed as previously described [24].

4.3 Immunoassay for IL-6

Sera were frozen and kept at –80°C. IL-6 serum level was quantified with an immunoassay kit (BioSource Cytoscreen human IL-6 UltraSensitive kit). The minimum detectable amount was 0.10 pg/ml.

4.4 Statistical analysis

Non-normally distributed IL-6 serum level was ln- transformed, as previously suggested [8]. General Linear Models (GLM) was employed to test hypothesis regarding the age-adjusted effects of binary factors (–174 C/G locus). When necessary, Bonferroni adjustment for multiple com- parisons was applied, and indicated by p . Allelic and adj genotypic frequencies were compared by Monte-Carlo £ 2, implemented in SPSS package (SPSS, Chicago, IL). HWE was calculated by Monte Carlo Markov Chain [25].

Terry, C. F., Loukaci, V. and Green, F. R., Cooperative influence of genetic polymorphisms on interleukin

transcriptional regula- tion. J. Biol. Chem.

:

–

Franceschi, C., Motta, L., Valensin, S., Rapisarda, R., zone, A., Berardelli, M., Motta, M., Monti, D., Bonafe`, M., Fer- rucci, L., Deiana, L., Pes, G.M., Carru, C., Desole, M.S., C., Sartoni, G., Gemelli, C., Lescai, F., Olivieri, F., F., Cardelli, M., Cavallone, L., Gueresi, P., Cossarizza, A., Troi- ano, L., Pini, G., Sansoni, P., Passeri, G., Lisa, R., Spazza- fumo, L., Amadio, L., Giunta, S., Stecconi, R., Morresi, R., Viticchi, C., Mattace, R., De Benedictis, G. and Baggio, G., Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians. Aging (Milano)

:

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Bruunsgaard, H., Pedersen, A. N., Schroll, M., Skinhoj, P. Pedersen, B. K., Impaired production of proinflammatory cyto- kines in response to lipopolysaccharide (LPS) stimulation in elderly humans. Clin. Exp. Immunol

:

–

De Benedictis, G., Rose, G., Carrieri, G., De Luca, M., Fal- cone, E., Passarino, G., Bonafe`, M., Monti, D., Baggio, G., Bertolini, S., Mari, D., Mattace, R. and Franceschi, C., Mito- chondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J.

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