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I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 All data produced in the present study are available upon reasonable request to the authors

Xinping Chen, PhD; Megha Talati, PhD; Joshua P. Fessel, MD, PhD; Anna R. Hemnes, MD; Santhi Gladson, MS; Jaketa French, BS; Sheila Shay, BS; Aaron Trammel, MD; John A. Phillips, MD, PhD; Rizwan Hamid, MD, PhD; Joy D. Cogan, PhD; Elliott P. Dawson, MS; Kristie E. Womble, BS; Lora K. Hedges, BS; Elizabeth G. Martinez, DO; Lisa A. Wheeler, BS; James E. Loyd, MD; Susan J. Majka, PhD; James West, PhD; Eric D. Austin, MD, MSCI

The molecular basis of familial isolated GH deficiency (IGHD) is heterogeneous. We have previously found a G → A transition in codon 20 of the GH gene that produces a stop codon and two donor splice site mutations (a T → C transition in the sixth base of IVSIII and G→ C transversion in the first base of IVS IV). The G→ C transversion, which destroys an HphI (GGTGA) restriction site at the exon IV/intron IV boundary (G/GTGA → G/CTGA), was found in a Saudi family with IGHD. To determine the frequency of this mutation among Saudi IGHD subjects, dried blood spots were analyzed from 12 additional Saudi cases from different families. The methodology involved a one-step PCR amplification of DNA obtained from 2 mm2 portions of dried blood spots which were collected on filter paper. These amplification products were then digested with HphI and analyzed on agarose gels. One subject was homozygous and the single, parental sample obtained was heterozygous for loss of this HphI site. Interestingly a simple repeat polymorphism adjacent to the GH gene differed between the two non-related Saudi subjects, who lacked the HphI site, suggesting that the GH mutaiions were independent. To determine if the GH mutations causing loss of the HphI site differed between the two Saudi IGHD cases, direct sequencing of the PCR products obtained from the filler paper samples was performed. In contrast 10 the firsi Saudi case which had a G→C transversion in the first base of IVS IV (G/CTGA) the second had a G→T transversion (G/TTGA). Analysis of the transcription products of the G→C mutation documented aberrant splicing and transcript analysis of the G→T mutation is being done for comparison. Our findings demonstrate 1) detection of GH splicing defects by restriction analysis and sequencing of DNA from dried blood spots and 2) 2/13 (15%) of Saudi IGHD subjects have IVS 3V donor splice site defects. These findings suggest that heterogeneous mutations which lead to transcript splicing errors may constitute a significant proportion of IGHD cases.

Absolute charge-transfer cross sections for collisions of protons with hydrogen and deuterium atoms have been measured within the energy range 0.1 to 150 eV using the merging-beams technique. The results are in excellent agreement with a fully quantum-mechanical treatment of this reaction. Earlier measurements which extended down to about 10 eV lie somewhat above the present values.