Genetic mechanisms of age regulation of human blood coagulation factor IX

Blood coagulation capacity increases with age in healthy individuals. Throu gh extensive Longitudinal analyses of human factor IX gene expression in tr ansgenic mice, two essential age-regulatory elements, AE5' and AE3', have b een identified. These elements are required and together are sufficient for normal age regulation of factor IX expression. AE5', a PEA-3 related eleme nt present in the 5' upstream region of the gene encoding factor IX, is res ponsible for age-stable expression of the gene. AE3', in the middle of the 3' untranslated region, is responsible for age-associated elevation in mess enger RNA Levels. In a concerted manner, AE5' and AE3' recapitulate natural patterns of the advancing age-associated increase in factor IX gene expres sion.