Analysis of the Effect of the Longevity Associated FOXO3 Genotype on Telomerase Activity in
a Japanese-Okinawan Cohort
Analysis of the Effect of the Longevity Associated FOXO3 Genotype on Telomerase Activity in a Japanese-Okinawan Cohort
Molecular Cell Biology
University of Hawai'i at Manoa
Forkhead box O3 (FOXO3) is one of the few genes that has consistently correlated across multiple long-lived populations to be associated with longevity. 1,2 In a previous study, an analysis of FOXO3 single nucleotide polymorphisms (SNP) identified a specific allele as being associated with less rapid shortening of telomeres, which is a molecular marker of longevity. 3 Telomeres are tandem repeats that shorten after each cell division, and telomerase is an enzyme that adds new tandem repeats, thereby extending the telomeres and the lifespan of the cell. 4 Because previous results have shown FOXO3 protects against telomere shortening, it is expected that telomerase activity will be higher in individuals that carry the longevity-associated allele of FOXO3. It is also expected that telomerase activity will be constant with age in the longevity-associated genotype. In this study, blood was extracted from 100 participants from a Japanese-Okinawan cohort, a notably long-lived population, and peripheral blood mononuclear cells were isolated. The genotype of each sample was obtained and telomeric repeat amplification assays were performed to quantify telomerase activity, as a function of genotype, sex, and age. Results indicate that telomerase activity decreases with age for the TT genotype, but do not decrease, to the same extent, with age for G-carriers. These findings provide insight as to how FOXO3 protects against telomere attrition and link the longevity-associated G-allele to modulated telomerase activity. Keywords: Longevity, FOXO3, telomerase
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