Accelerated Biological Aging in Familial Pulmonary Fibrosis

Since Familial Pulmonary Fibrosis (FPF) manifests in older adults and telomere attrition is common in FPF and sporadic Idiopathic Pulmonary Fibrosis (IPF), we postulated that accelerated aging, as determined by epigenetic clock (DNA methylation) measurements, could occur in FPF. We measured DNAge from blood of patients with FPF and a group of first-degree relatives of FPF patients without disease (termed "at-risk" for FPF) with or without genetic rare variants (RVs) in telomerase pathway genes. We observed accelerated epigenetic aging with increased DNAge compared to chronological age in individuals at-risk for FPF and FPF patients compared to healthy controls. We found that increased DNAge manifests independently of the presence of RVs in telomerase pathway genes or telomere length in peripheral blood cells. These findings suggest that increased DNAge could be an independent risk factor for the development of FPF.