Sex and Age Specificity of Susceptibility Genes Modulating Survival at Old Age

Abstract

Objective: We aimed to investigate the influence of the genetic variability of candidate genes on survival at old age in good health. Methods: First, on the basis of a synthetic survival curve constructed using historic mortality data taken from the Italian population from 1890 onward, we defined three age classes ranging from 18 to 106 years. Second, we assembled a multinomial logistic regression model to evaluate the effect of dichotomous variables (genotypes) on the probability to be assigned to a specific category (age class). Third, we applied the regression model to a cross-sectional dataset (10 genes; 972 subjects selected for healthy status) categorized according to age and sex. Results: We found that genetic factors influence survival at advanced age in good health in a sex- and age-specific way. Furthermore, we found that genetic variability plays a stronger role in males than in females and that, in both genders, its impact is especially important at very old ages. Conclusions: The analyses presented here underline the age-specific effect of the gene network in modulating survival at advanced age in good health.

PTK2 rs7460 and rs7843014 Polymorphisms and Exceptional Longevity: A Functional Replication Study

“…Finally, our finding that there were essentially no sex-related differences in the possible effect of PTK2 gene variants on EL remains to be corroborated in other cohorts. Passarino et al 48 showed that genetic factors influence survival at advanced age in a sex-specific way, with genetic variability playing a stronger role in males than in females.…”

The Effect of ACP1-ADA1Genetic Interaction on Human Life Span

“…The sample study was divided into three sex-specific age classes ( the age classes of women are written in square bracket) The first age class was made by men with age <66 [<73], the second class by men with age 66-88 [73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91], and the third class by men with an age >88 [>91]. These gender-specific age classes were defined according to demographic information and accounted for different survivals of men and women in Italian population (Passarino et al 2006). The study protocol was approved by the Joint Ethical Committee (JEC) University of Camerino-Azienda ASUR Marche Camerino, in accordance with the Declaration of Helsinki in its revised edition and with international and local regulatory requirements.…”

MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case–control study using a multilocus genotyping

“…Indeed, genome-wide association studies (GWAS) are at present widely used to find genetic variants contributing to variation in human lifespan (Puca et al 2001;Lunetta et al 2007;Newman et al 2010;Walter et al 2011;Deelen et al 2011;Nebel et al 2011;Malovini et al 2011). Along with GWAS, studies that consider candidate biochemical pathways consisting of many biologically related genes, and a minimal number of "tagging" SNPs that efficiently capture all the common genetic variation in the assayed genomic region, are also being routinely used (Passarino et al 2006;Nebel et al 2009;Pawlikowska et al 2009;Flachsbart et al 2010).…”