{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:58:52Z","timestamp":1793674732298,"version":"4.5.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,2]]},"abstract":"<jats:p>\n                    Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis (IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. Short telomeres limit tissue renewal capacity in the lung and germ-line mutations in telomerase components,\n                    <jats:italic>hTERT<\/jats:italic>\n                    and\n                    <jats:italic>hTR<\/jats:italic>\n                    , underlie inheritance in a subset of families with IPF. To examine the hypothesis that short telomeres contribute to disease risk in sporadic IIPs, we recruited patients who have no family history and examined telomere length in leukocytes and in alveolar cells. To screen for mutations, we sequenced\n                    <jats:italic>hTERT<\/jats:italic>\n                    and\n                    <jats:italic>hTR.<\/jats:italic>\n                    We also reviewed the cases for features of a telomere syndrome. IIP patients had shorter leukocyte telomeres than age-matched controls (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). In a subset (10%), IIP patients had telomere lengths below the first percentile for their age. Similar to familial cases with mutations, IPF patients had short telomeres in alveolar epithelial cells (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Although telomerase mutations were rare, detected in 1 of 100 patients, we identified a cluster of individuals (3%) with IPF and cryptogenic liver cirrhosis, another feature of a telomere syndrome. Short telomeres are thus a signature in IIPs and likely play a role in their age-related onset. The clustering of cryptogenic liver cirrhosis with IPF suggests that the telomere shortening we identify has consequences and can contribute to what appears clinically as\n                    <jats:italic>idiopathic<\/jats:italic>\n                    progressive organ failure in the lung and the liver.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0804280105","type":"journal-article","created":{"date-parts":[[2008,8,27]],"date-time":"2008-08-27T21:39:48Z","timestamp":1219873188000},"page":"13051-13056","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":735,"title":["Short telomeres are a risk factor for idiopathic pulmonary fibrosis"],"prefix":"10.1073","volume":"105","author":[{"given":"Jonathan K.","family":"Alder","sequence":"first","affiliation":[{"name":"Departments of *Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian J.-L.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85287;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Departments of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonye","family":"Danoff","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-chih","family":"Su","sequence":"additional","affiliation":[{"name":"the \u2016Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy D.","family":"Cogan","sequence":"additional","affiliation":[{"name":"**Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Vulto","sequence":"additional","affiliation":[{"name":"Terry Fox Laboratory, British Columbia Cancer Agency, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin M.","family":"Tuder","sequence":"additional","affiliation":[{"name":"Pathology, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John A.","family":"Phillips","sequence":"additional","affiliation":[{"name":"**Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Lansdorp","sequence":"additional","affiliation":[{"name":"Terry Fox Laboratory, British Columbia Cancer Agency, and"},{"name":"Department of Medicine University of British Columbia, Vancouver, BC, Canada V5Z 1L3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Loyd","sequence":"additional","affiliation":[{"name":"Departments of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Y.","family":"Armanios","sequence":"additional","affiliation":[{"name":"Departments of *Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,9,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.2.ats01"},{"key":"e_1_3_3_2_2","first-page":"S47","article-title":"Pulmonary fibrosis in families","volume":"29","author":"Loyd JE","year":"2003","unstructured":"JE Loyd, Pulmonary fibrosis in families. Am J Respir cell Mol Biol 29, S47\u2013S50 (2003).","journal-title":"Am J Respir cell Mol Biol"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200408-1104OC"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200112-123OC"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066157"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701009104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508124102"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80006-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.11.020"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1346"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02118"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/345458a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/33345"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90170-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90576-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5328.955"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/35096585"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042980"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.02109.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)07040-4"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-32"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/990141"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-075598"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80687-X"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0335"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-120907"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm111"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.10.004"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2007.00721.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5456.1253"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.263"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62553-9"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708032200"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506319200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600952"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0804280105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:14:33Z","timestamp":1649783673000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0804280105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,2]]},"references-count":35,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2008,9,2]]}},"alternative-id":["10.1073\/pnas.0804280105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0804280105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1123109.793497150","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1123109.580232","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,2]]},"assertion":[{"value":"2008-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}