allele T in middle-aged subjects, indicating a possible protective role of the allele A in aging. Our results support the hypothesis that longevity is the result of a well-functioning immune system and a hyper-expression of anti-inflammatory genes of immunity. The genetic regulation of inflammatory processes may influence the presence of age-related disorders. 

In recent decades, there have been significant improvements in health and longevity, resulting in centenarians becoming the fastest-growing population group. Human lifespan is influenced by environmental, genetic, and accidental factors. Research has shown that advanced glycation end products (AGEs) may play a role in physiological aging processes. AGEs could be involved through the formation of free radicals or through molecular interaction with their specific surface receptor (RAGE). This study aimed to investigate differences in the frequencies of 374T/A polymorphism in subjects aged over 90 years and middle-aged individuals. 

The study population included 254 Caucasian subjects (170 women and 84 men), with subjects aged over 90 years (n = 119) and subjects aged 18 to <80 years as controls (n = 135). The genotypic and allelic distributions of the 374 T/A polymorphism were reported, with no significant differences found between middle-aged individuals and the long-living group. However, an association was observed between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. 

Stepwise regression analysis showed that RAGE polymorphism remained related to the manifestation of heart disease even after adjusting for confounding variables. The correlation analysis showed that gender significantly correlated with polymorphism, with a higher frequency of homozygous AA genotype in male subjects aged over 90 years than in subjects aged <80 years. No differences were found as regards the TT genotype. 

In conclusion, our results suggest that longevity is related to a well-functioning immune system and hyper-expression of anti-inflammatory genes of immunity. The genetic regulation of inflammatory processes may influence the presence of age-related disorders. The A allele and genotype homozygous for this allele (AA) may have a protective role in aging, particularly in males. These findings may contribute to further research on the genetic mechanisms underlying longevity.distribution, otherwise as median and interquartile range (25th-75th percentile). Categorical variables are expressed as proportions. Differences between groups were analyzed by t-test or Mann-Whitney test for continuous variables and chi-squared test for categorical variables. Logistic regression analysis was performed to test the association between the RAGE 374T/A polymorphism and the likelihood of being a long-living subject. All statistical analyses were performed using SPSS version 22.0 (IBM Corp, Armonk, NY, USA). A p-value <0.05 was considered statistically significant.Distribution and median were used to analyze variables with non-normal distribution. The Student t-test for paired samples was used for data analysis. Categorical variables were reported as absolute (n) and relative (%) frequencies. The chi-square test was used to evaluate associations between categorical variables. Statistical significance was defined as p < 0.05.

Our research revealed a higher prevalence of the AA genotype in the male population of subjects aged 90 years who have reached that age in good health. These results confirm the hypothesis that longevity is the result of good immune system functioning and a presumable hyper-expression of anti-inflammatory genes of immunity variants. Genetic regulation differences in inflammatory processes may influence the presence of age-related disorders. Surprisingly, the prevalence of the AA genotype is lower in the long-living female population than in the male population, where this genotype seems to have a more protective role. Therefore, the AA genotype would not seem to determine better aging in females. In the general population, women live longer than men, so it is worth considering whether the endocrine system can have a protective role even in those subjects without this genotype. Further research is necessary to identify other agents involved in healthy aging.

Conflicts of Interest: The authors declare no conflict of interest.