NS: not significant; *p<0.05, **p<0.01, ***p<0.001. ACE: angiotensin-converting enzyme; PON: paraoxonase; PON : basal (1) paraoxonase activity; PON : stimulated paraoxonase activity. (2)

more retarded in the aging process than Gln homozygous carriers (related to low paraoxonase activity). Regarding apoE, LPL and MTHFR polymorphisms, results obtained after pooling heterozygous and homozygous subjects, as described in Methods, were not different from those ob- tained in keeping the three most frequent apoE, LPL or MTHFR genotypes. The only observed difference con- cerns PON polymorphism, presenting a co-dominance of the two alleles (Table 3).

coefficients were negative for PON and arylesterase ac- tivities, suggesting that elevated PON activity leads to a de- lay in the aging process, whereas TC, TG and apoB concentrations lead to acceleration (Table 4).

To further quantify the association between the AI and the studied variables, multiple regression analysis was applied to estimate the percentage of variation of the AI explained by serum variables significantly found asso- ciated with the AI value. Only PON basal activity and TG concentration were related to AI variance (Table 5). PON activity alone explained 7.12% of the AI with (1) TG concentration 13.6%.

TC, TG and apoB concentrations were significantly and positively correlated with the AI, whereas PON [PON (1) and PON ] and arylesterase activities were significantly (2) and negatively associated with the AI (p<0.05). Regression

3 - Mean values of the aging indicator (AI) according to

Gene candidates Genotypes p-value APOE ε2/ε3 ε3/ε3 ε3/ε4 AI -2.46 -0.45 -0.29 0.34 (NS) LPL(447) C/C C/G G/G AI -0.73 -0.93 -0.26 0.96 (NS) PON(192) Gln/Gln Gln/Arg Arg/Arg AI 0.26 -1.83 -0.53 0.0486* PON(192) Gln/Gln Gln/Arg+ Arg/Arg AI 0.26 -1.57 0.0237* ACE(I/D) I/I I/D D/D AI -0.56 -0.74 -0.89 0.96 (NS) CBS(278) Ile/Ile Ile/Thr AI -0.67 -1.25 0.61 (NS) MTHFR(677) C/C C/T T/T AI -0.16 -1.00 -1.82 0.38 (NS)

NS: not significant; *p<0.05. APOE: apolipoprotein E; LPL: lipoprotein lipase; PON: paraoxonase; ACE: angiotensin-converting enzyme; CBS: cystathionine β-synthase; MTHFR: methylenetetrahydrofolate reductase.

Table 5 - Multiple regression analysis on the aging indicator in men.

who did not find relations between common PON gene variants (Met55Leu, Arg192Gln) and the risk of car- diovascular mortality in a cohort of elderly people aged 85 years and over. In addition, we did not find over-rep- resentation of the Arg allele in this sample population, compared with the frequencies found in Caucasian populations.

Independent variables β s R2×100 PON (nmol/mn/mL) -0.0207 0.0054 7.12 (1) Triglycerides (mmol/L) 2.718 0.801 13.6

β: regression coefficient; s: standard deviation of β; R2: variance explained. PON : basal paraoxonase activity. (1)

The association of TG concentration with the AI found in this study is also a new result. Besides, we re- ported a decrease in the TG concentration in a popu- lation of subjects with AD, when values were com- pared with those of control subjects of the same age (un- published data). This result is independent of the com- mon genetic polymorphism of apoE, and may be linked to the more general nutritional habits and energy metabolism of middle-aged subjects. In contrast, we could not find associations between apoE and ACE polymorphisms with aging in this French sample pop- ulation, as observed in other studies in French cente- narians (1, 7). These authors demonstrated that apoE ε4 is associated with a shorter life expectancy, as this iso- form correlates with increased susceptibility for both CVD and AD, and that apoE ε2 is more frequent in long-lived individuals (1, 7). They also found that the ACE (DD) genotype is associated with increased life expectancy (1), but this finding was refuted by a recent study by Blanché et al. (7).

DISCUSSION

In this study, we used a statistical indicator, AI, to study the association of serum lipid parameters and six ge- netic polymorphisms with aging, in a group of healthy el- derly men around 70 years old. The construction of this aging indicator has been fully described elsewhere (14). The sample population used here was based on a larger study named Stanislas Cohort (25), in which some grand- parents were included. Since not enough women qualified as subjects, we could only use the male group.