Paraoxonase activity and genotype predispose to successful aging

Area of Science:

• Genetics
• Biochemistry
• Gerontology

Background:

• The paraoxonase 1 (PON1) codon 192 R allele is associated with successful aging.
• Understanding the interplay between PON1 genotypes, activity, and aging is crucial for gerontological research.

Purpose of the Study:

• To investigate the relationship between PON1 genotypes, enzymatic activity, and mass concentration across a wide age range.
• To specifically examine these relationships in nonagenarian and centenarian participants to understand longevity.
• To determine if PON1 genetic variability influences paraoxonase activity and contributes to the longevity phenotype.

Main Methods:

• Evaluated PON1 genotypes, enzymatic activity, and mass concentration in 229 participants aged 22-104.
• Focused analysis on nonagenarian and centenarian subgroups.
• Employed multinomial regression logistic models to assess the contribution of PON1 parameters to longevity.

Main Results:

• Found genetic control of paraoxonase activity, maintained throughout life, including in extreme age groups.
• Observed a significant decrease in paraoxonase activity with aging.
• Identified significantly higher paraoxonase activity in R+ and M- carriers compared to other genotypes.
• Demonstrated that paraoxonase activity and specific PON1 genotypes (R+ and M-) significantly explain the longevity phenotype.

Conclusions:

• Genetic variability at the PON1 locus significantly influences paraoxonase activity across the lifespan.
• Both PON1 genetic variability and resulting paraoxonase activity levels appear to be important factors in survival at extreme advanced ages.
• The study supports a role for PON1 in the aging process and longevity.