Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively.
Paraoxonase (PON), an HDL- associated enzyme, may protect against the development of atherosclerosis. Single nucleotide polymorphisms of PON have been reported to be associated with an incidence of coronary heart diseases. We investigated the effect of PON R192Q variants on serum lipid profile after caloric restriction in nondiabetic healthy males. After caloric restriction for 12 weeks, the levels of high-density lipoprotein cholesterol (HDL-C) increased in the subjects carrying RR genotype, but not in the QR and QQ genotypes.
Caloric restriction (CR) has been shown to attenuate age-related oxidative damage and to improve major atherosclerotic risk factors. Paraoxonase 1 (PON1), an enzyme specifically associated with HDL containing apolipoproteins A-I and J, has been reported to prevent the proatherosclerotic effects of oxidized LDL. The aim of this study was to evaluate whether modulation of PON1 activity is part of the underlying CR mechanisms that attenuate the age-associated negative effects.