engleski

Reaching 95.0 years of age: The genetic association in the elderly Croatian population

Human longevity is influenced both by genetic and non-genetic factors, and genetic variability accounts for approximately 25% of variation in life expectancy. Genes that can positively influence lifespan and the ageing process are known as longevity genes. We aimed to elucidate single nucleotide polymorphisms (SNPs) that are significantly related to longevity as defined by the cut-off age of 95.0 (the threshold age for extreme longevity) in a sample of elderly persons of European origin. The study sample comprised of 314 unrelated individuals from Croatia who were above 85.0 years of age when the data were collected. As the sample of long-lived individuals was gathered in the period between 2007 and 2009, the age at death for each individual has been determined from the national mortality register 10 years after the initial sampling. This enabled us to differentiate between truly long-lived individuals that had survived beyond 95 years of age, and those that died before reaching 95 years, thus elucidating which SNPs are a key component for extreme longevity in the Croatian population. Genotype data were obtained for 42 SNPs from 28 putative longevity genes, which were selected due to strong and/or replicated association to human longevity and their role in different signalling pathways of cellular ageing and senescence. Univariate and multivariate logistic regression were performed with genotypic data coded as: 2 = longevity allele homozygotes ; 1 = heterozygotes ; 0 = non-longevity allele homozygotes. Out of the initial 42 SNPs, 10 SNPs that reached the inclusion criteria of having a p-value of p < 0.2 in univariate logistic regression entered the series of multivariate logistic regressions. The best model, explaining 9.3% of the variance for the survival to the age of 95.0, consisted of five SNPs. Three SNPs that were significantly (at p < 0.05 level) associated with reaching 95.0 years of age are PTPN1 rs6067484, PAPPA rs4837525, and TP53 rs1042522. Two remaining SNPs were marginally significant (APOE rs429358 ; p = 0.053) or not significant (IRF4 rs12203592) but they both contribute to the strength of the model. Although the best model explains a considerable proportion of variance for surviving up to the 95-years-of- age phenotype, the modest associations of particular SNPs warrant replication in more powered studies. (CSF grant IP 01-2018-2497: HECUBA)

extreme longevity ; longevity genes ; single nucleotide polymorphisms ; logistic regression analysis ; survival ; oldest-olds ; Croatia

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