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We used a novel high\u2010throughput proteomics approach to identify serum peptides and proteins associated with 5\u2010year mortality in community\u2010dwelling men age \u226565\u00a0years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: Mr<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography\u2013ion mobility\u2013mass spectrometry, and incident mortality in the subsequent 5\u00a0years was ascertained by tri\u2010annual questionnaire. Rigorous statistical methods were utilized to identify 56 peptides (31 proteins) that were associated with 5\u2010year mortality. In an independent replication phase, selected reaction monitoring was used to examine 21 of those peptides in baseline serum from 750 additional men; 81% of those peptides remained significantly associated with mortality. Mortality\u2010associated proteins included a variety involved in inflammation or complement activation; several have been previously linked to mortality (e.g., C\u2010reactive protein, alpha 1\u2010antichymotrypsin) and others are not previously known to be associated with mortality. Other novel proteins of interest included pregnancy\u2010associated plasma protein, <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin, leucine\u2010rich \u03b1\u20102 glycoprotein 1, vinculin, vitronectin, mast\/stem cell growth factor receptor, and Saa4. A panel of peptides improved the predictive value of a commonly used clinical predictor of mortality. Overall, these results suggest that complex inflammatory pathways, and proteins in other pathways, are linked to 5\u2010year mortality risk. This work may serve to identify novel biomarkers for near\u2010term mortality.<\/jats:p>","DOI":"10.1111\/acel.12717","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T08:36:37Z","timestamp":1517819797000},"source":"Crossref","is-referenced-by-count":31,"title":["High\u2010throughput serum proteomics for the identification of protein biomarkers of mortality in older men"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-7355","authenticated-orcid":false,"given":"Eric S.","family":"Orwoll","sequence":"first","affiliation":[{"name":"Oregon Health &amp; Science University Portland OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Wiedrick","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University Portland OR 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