A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study.

BACKGROUND: An attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (IGF-1R). METHODS: In an elderly population from North-eastern Italy (n = 668 subjects, age range 70-106 years) we investigated the IGF-1R polymorphism G3174A (rs2229765) and the plasma concentration of free IGF-1. Frequency distributions were compared using chi2-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at alpha = 0.05. RESULTS: Males showed an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between rs2229765 genotype and IGF-1 in the females. CONCLUSION: These findings confirm the importance of the rs2229765 minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.

Interleukin-6 plasma level increases with age in an Italian elderly population ("The Treviso Longeva"-Trelong-study) with a sex-specific contribution of rs1800795 polymorphism.

The transcription rate of interleukin-6 (IL-6) can be reduced by the C-allele of a polymorphism (rs1800795) located in the 5'-flanking region of the IL-6 gene (NM_000600), and IL-6 plasma levels increase with age. We assembled an elderly Italian population ["The Treviso Longeva (Trelong) study", age range 70-106 years, n = 668 subjects] and assessed rs1800795 genotype and plasma IL-6 concentrations. The rs1800795 genotype was also assessed in an independent Italian study ("Milan" study, age range 70-96, n = 245 subjects). To verify an age- or sex-specific effect of rs1800795 genotype we compared people younger (70-85) and older (85+) than 85 years of age. We found a significant reduction in the frequency of rs1800795 C/C genotype in 85+ men from the Trelong study, while in the Milan study this data did not reach significance. However, considering the two studies together, the frequency of the rs1800795 C/C genotype was significantly lower in 85+ than in 70-85 males (4.0% and 10.7%, respectively), while it remained unchanged in females. As for IL-6 plasma levels, after a multivariate analysis to control for confounders, a correlation between age and plasma IL-6 concentrations was revealed (P < 0.0001). An increase in circulating IL-6 levels in the entire 85+ group compared to the 70-85 group (P < 0.05, Tukey's test) was also noticed. We suggest a sex-specific pattern for genetic variability linked to inflammatory response and longevity, consistent with the age-related increase in IL-6.