Hemophilia is associated with accelerated biological aging.

Abstract

Hemophilia is a rare X-linked bleeding disorder caused by mutations in the F8 or F9 gene (hemophilia A or B), leading to deficient factor VIII or IX proteins, respectively. Hemophilia-related complications caused by bleeding into the joints (the hallmark of hemophilia) and age-related comorbidities occur frequently and impact the functionality and quality of life of persons with hemophilia (PwH). Given the chronic nature of hemophilia, we hypothesized that hemophilia has an association with accelerated biological aging. Therefore, we investigated biological aging biomarkers, i.e. telomere length and mitochondrial DNA (mtDNA) copy number with a quantitative-PCR-based assay in PwH (n=99) and age- and sex-matched healthy controls (n=61). The association of telomere length and mtDNA copy number with hemophilia severity was investigated using ordinary-least-squares linear regression models allowing for interactions with chronological age. Telomere length (6.09 [4.79-7.68] kb vs. 10.07 [7.93-12.66] kb, p.