Polymorphism of the Forkhead box-O3 (FOXO3) Longevity Gene rs2802292 and senescence-associated secretory phenotype (SASP) in Indonesian Elderly Population

Abstract

BACKGROUND: Forkhead box O3 (FOXO3) is a transcription factor that regulates stress resistance, metabolism, cell cycle, and apoptosis. Several studies exhibited the association of the FOXO3 polymorphism rs2802292 with human longevity and protects individuals from degenerative diseases. The emergence of degenerative diseases in the elderly is associated with the accumulation of senescent cells that secrete a secretome known as a senescence-associated secretory phenotype (SASP) consists of several cytokines, chemokines, growth factors, proteases. OBJECTIVE: The aim of this research was to analysis polymorphism of FOXO3 gene rs2802292 G-allele and its impact to the SASP by measuring IL-1α, IL-6, IL-8, and IL-10 in Indonesian elderly populations. METHODS: This study was conducted on 92 elderly subjects living at Jakarta. DNA was isolated from the whole blood then continued with PCR and sequencing for FOXO3 rs2802292 analysis. SASP was analyzed from the plasma using Luminex. Statistical analysis was performed using ANOVA and Kruskal Wallis. RESULTS: The results showed that FOXO3 rs2802292 was detected in Indonesian elderly population as follows GG, GT, TT genotype frequencies were 17.4 %, 42.4 % and 40.2 % respectively. Meanwhile, G and T allele frequencies based on the Hardy-Weinberg equilibrium test were 0.385 and 0.615 respectively. GG genotype was significantly found in subjects with longevity. Nevertheless, SASP analysis was found no significant differences both among GG, GT, TT genotypes. CONCLUSION: The frequency of FOXO3 rs2802292 G-allele in Indonesian elderly population was 0.385 and significantly detected in subjects with longevity. However, the FOXO3 rs2802292 polymorphism did not affect cytokines level as the component of SASP.