In conclusion, our study demonstrates that genetic variation in PPARG-2 is associated with human longevity through its effect on body composition. The Pro/Ala genotype appears to be gender-specific in its association with BMI and insulin resistance degree. Our results highlight the importance of genetic factors in determining human longevity and suggest potential targets for intervention in age-related disorders.The article discusses the association of PPARG genotype with obesity and type 2 diabetes and its effect on longevity. Previous studies have investigated this association in different populations, but the results suggest that survival selection through Pro/Ala locus is differentially affected in males and females. The sex-specific association of longevity with alleles or genotypes of several genes related to risk factors for age-related diseases, including PPARG genotype, is not unexpected based on previous studies on the genetics of longevity in centenarians. Despite the finding that several genes have been found associated with longevity in both genders, different findings in males and females have been observed in previous gene/longevity association studies, pointing out that gender is a major variable in the genetics of longevity and suggesting that men and women follow different strategies to reach longevity. To this regard, it has been hypothesized that female centenarians are more likely to reach 100 years of age because of a more favorable environmental condition and a healthier lifestyle.

The Pro/Ala variant in the peroxisome proliferator-activated receptor gamma (PPARG) has been extensively investigated for association with obesity in two Caucasian populations. Diabetes Blanquart et al. Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. J. Steroid Biochem. Biol. The effect of Pro/Ala polymorphism on body composition appears to be gender-specific, which suggests that it affects human longevity.

Intriguingly, the fact that longevity is associated with an increased heterozygosity at PPARG locus is in agreement with previous findings suggesting a survival advantage for heterozygotes. Loss of heterozygosity is frequent in a number of non-endocrine tumors and in a few endocrine tumors, and its presence can correlate with tumor aggressiveness and survival. Naturally, caution must be exercised in interpreting these novel findings.

In conclusion, the study demonstrated that paraoxonase Pro/Ala gene polymorphism is associated with human longevity. Such an effect is probably due to the effect of Pro/Ala polymorphism on body composition and appears to be gender-specific.

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