Experimental Gerontology
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The intron interferon-gamma gene and group po Italian Mt CETTee TEE UIstituto | EE MEPIS Nazionale > di] MP EEi Ricovero re Cura dell'Anziano, EMA GEE_ Ancona, | ee ENA EEA, Italy

Received, June 7 .//,0; received in lint 1 revised form ./ September .//,0; accepted 7 .1 September 4 .//

Abstract

SABA Oe cardiovascular diseases, LILLIES, neurodegeneration, ONE J OED NN, osteoarthritis < s and osteoporosis, and diabetes. Thus, it is hypothesized that genetic variations in pro-EN ENON SE:r anti-inflammatory cytokines might influence successful ageing and longevity. 75 NN IE have Jr> studied the distribution of +874T - ae ren> Ai interferon-gamma in a large number of Italian BNE ON ED1 centenarians to evaluate if the two alleles might be differently represented in people selected for longevity. I ee Oe.DNAs samples Were obtained from 11741 Italian centenarians (8;; cae) years old (NEE DT women and men); and from 248 PN BNI NENT 0 OA/ <60-year-old oe NEN OT control beesubjects (8;/ women and men) matched for geographical distribution. EM LEO IEEPolymorphisms at +874 were identified using an amplification refractory mutation FINESsystem EEE eeemethodology. The +874T z allele was found less frequently in centenarian women than in centenarian men and control women whereas significant differences were observed in the distribution of the two alleles between male or female. Allele frequencies in centenarian women were not found significantly different from male controls. Possession of the +874A allele, known to be associated with low IFN-y production, significantly increases the possibility to achieve extended longevity, suggesting that the pro-inflammatory status characteristic of ageing may be detrimental for successful ageing. The datum that the oore allele was significantly increased in female but not in male centenarians strengthens the idea that gender may be a major variable in the biology of ageing. However, the data add another piece of evidence to the complex puzzle of genetic and environmental factors involved in controlling human life span expectancy. Thus, studies on cytokine gene polymorphisms may promise to individuate a complex network of trans-interactive genes able to influence the type and strength of responses to environmental stressors and as a final result, thereby conditioning individual life expectancy. //. Elsevier Science Inc. All rights reserved.

Keywords: Interferon-gamma; Longevity; Inflammation; Centenarians; Immunogenetics

Introduction