Surprisingly, the significant association of PON ge- netic polymorphism at codon 192 with aging was in- teresting, as subjects carrying the Arg allele had a bio- logical age 1.5 years below their chronological age. These results suggest that higher PON activity is better for “successful” aging. This seems clear, since PON is an enzyme bound to HDL sub-fractions and may provide protection essentially through hydroperoxide hydrolysis in the antiatherogenic properties of HDL by avoiding ox- idative lipoprotein modifications (26). However, some re- ports found a relationship between the Arg allele (high PON activity) and higher serum TG and apoB, but low- er TC and LDL-C concentrations. Thus, the respective roles of PON Arg allele and PON activity are complex in association with CVD. Epidemiological studies carried out in healthy subjects, patients with angiographically documented CVD, and non-insulin dependent diabetes mellitus (NIDDM) patients having or not a history of CVD led to over-representation of the Arg allele in CVD patients and in NIDDM patients with CVD (12, 13). Other studies suggest that the Arg allele is associ- ated with increased risk for CVD, whereas others did not show evidence of associations between the Arg 192 Gln polymorphism of PON and either myocardial or CVD risk. However, in this study, we do not show statistical and significant differences in lipid profiles between var- ious PON genotypes (data not shown). The observed as- sociation between PON polymorphism and the mean AI values obtained in each PON genotype may partly be ex- plained by the multiple implications of PON polymor- phism in lipid metabolism and by the new physiological role of PON activity in the hydrolysis of lipid hy- droperoxides generated in lipoproteins upon oxidative

and the AI may be explained by the age difference (about 30 years) between our study and the two above studies on French centenarians. Many studies fail to show an association between MTHFR polymorphism and longevity in European populations (28). However, Heijmans et al. (29) found a decrease in the allele fre- quency of MTHFR 677T in an elderly European original population compared with young controls (4.4 vs 12.2%), and concluded that an association of this gene variant (677T) leads to a risk of mortality 3.7-fold high- er in elderly subjects. Perhaps our sample size pre- vented us from obtaining the same results. Meanwhile, to our knowledge, no study has investigated the asso- ciation of CBS and LPL polymorphisms with aging, and we did not demonstrate any significant associa- tion in this study.

Besides the fact that TC is part of the estimate of BA, significant correlations of TC, TG and apoB concen- trations with the AI may be due to their implication in CVD, which reduces successful aging. However, Kervi- nen et al. (6) found concentrations of TC and LDL-C to be lower in the elderly population. The work of Strand- berg et al. (30) also showed a decreased concentra- tion of TC with age in an elderly population, perhaps ex- plained by less physical activity, or by changes in nutri- tional status, and the lower need for lipids in the metabolism in the elderly population.

CONCLUSIONS

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