Accelerated Biological Aging in Familial Pulmonary Fibrosis

Abstract 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement 5K12HD043483-12 P01HL172729 Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: These studies were approved by the Vanderbilt University Institutional Review Board (IRB# 020343, 080780). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Competing Interest Statement: The authors declare no competing interest. Impact: Aging is a significant risk factor for pulmonary fibrosis. Determining the epigenetic clock’s influence in FPF could help identify people at higher risk for disease. Our findings show accelerated epigenetic age in individuals “at risk” for FPF and FPF patients compared to healthy controls. Data Availability All data produced in the present study are available upon reasonable request to the authors