Five gene variants in nonagenarians, centenarians and average individuals

Abstract

IntroductionGenetic factors contribute to the variation of human life span which is believed to be more profound after 85 years of age. The aim of the present study was to evaluate the frequency of 5 gene polymorphisms between nonagenarians, centenarians and average individuals.Material and methodsSingle nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT; rs2736098), insulin-like growth factor-1 binding protein-3 (IGFBP3; A-202C, rs2857744), fork-head box O3A (FOXO3A; rs13217795 and rs2764264) factor and adiponectin (ADIPOQ; rs2241766) were evaluated in 405 individuals: n = 256 nonagenarians and centenarians (study group) and n = 149 average lifespan individuals (control group aged 18 – < 80 years).ResultsThe frequency of women was significantly higher in the study group than the control group (64.5 vs. 49.7%, p = 0.004). Genotypic and allele frequencies did not differ between groups according to gender. However, in men, the frequency of TT genotype of FOXO3A; rs2764264 was higher in the study group than the control group (45.6 vs. 28.0%, p = 0.05). Overall, the frequency of the C allele of FOXO3A; rs2764264 was significantly lower in the study group than the control group (3.9 vs. 9.5%, respectively, p = 0.023). Furthermore, in the study group, the T allele was significantly more frequent in the nonagenarians (n = 239) than the centenarians (n = 17) in both FOXO3A; rs13217795 and rs2764264 (64.4 vs. 44.1%, p = 0.018 and 69.7 vs. 50.0%, p = 0.017, respectively).ConclusionsAccording to survival status, there is differentiation in the prevalence of both studied FOXO3A gene polymorphisms. The study group had half of the C alleles compared with the control group and centenarians less frequently had the T allele of both FOXO3A gene polymorphisms compared with nonagenarians. No difference was found between groups according to TERT, IGFBP3 and ADIPOQ gene polymorphisms. It seems that some polymorphisms may be significant in prolonging our lifespan. Nevertheless, confirmation in additional study populations is needed.

Genetic polymorphism of CYP3A4 is associated with poor response to ifosfamide treatment in children with solid embryonic tumors

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Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules That Affect Aging Pathways and Extend Caenorhabditis elegans’ Lifespan

“…. In humans, exceptional longevity-associated FOXO3A polymorphisms have been identified in multiple cohorts (Kenyon 2010;Joshi et al 2017;Kolovou et al 2017), and NRF2 activation and mTOR inhibition have been shown to delay senescence in human fibroblasts (Kapeta et al 2010;Walters et al 2016). As proof of concept, genetic screens for organismal stress resistance in yeast, worms and plants have enriched for mutants that live long (de Castro et al 2004;Kim and Sun 2007;Kennedy et al 1995;Cao et al 2003).…”

Angiotensin-Converting Enzyme (ACE) genetic variation and longevity in Peruvian older people: a cross-sectional study

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