@article{94b06590995148d0abdbe97a40f4f5c1,
title = "High-throughput serum proteomics for the identification of protein biomarkers of mortality in older men",
abstract = "The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography–ion mobility–mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire. Rigorous statistical methods were utilized to identify 56 peptides (31 proteins) that were associated with 5-year 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-associated proteins included a variety involved in inflammation or complement activation; several have been previously linked to mortality (e.g., C-reactive protein, alpha 1-antichymotrypsin) and others are not previously known to be associated with mortality. Other novel proteins of interest included pregnancy-associated plasma protein, VE-cadherin, leucine-rich α-2 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-year mortality risk. This work may serve to identify novel biomarkers for near-term mortality.",
keywords = "aging, biomarker, inflammation, men, mortality, proteomics",
author = "{for the Osteoporotic Fractures in Men Study (MrOS) Research Group} and Orwoll, {Eric S.} and Jack Wiedrick and Jon Jacobs and Baker, {Erin S.} and Paul Piehowski and Vladislav Petyuk and Yuqian Gao and Tujin Shi and Smith, {Richard D.} and Bauer, {Douglas C.} and Cummings, {Steven R.} and Nielson, {Carrie M.} and Jodi Lapidus",
note = "Funding Information: The MrOS Study is supported by the following institutes under the National Institutes of Health (NIH): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Center for Advancing Translational Sciences (NCATS), and NIH roadmap for Medical Research under the following grant numbers: U01AR45580, U01AR45614, U01AR45632, U01AR45647, U01AR45654, U01AR45583, U01AG18197, U01AG027810, and UL1RR024140, P50 AR063043, and endowment to the Center of Musculoskeletal health, UC Davis. The proteomics measurements were supported by the National Institutes of Health (NIH) NIGMS Grant P41 GM103493 (RDS) and were performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy (DOE) national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is operated by Battelle for the DOE under Contract DE-AC05-76RL0 1830. Proteome data analysis was further supported by the preceding grant as well as NIH/NCATS grant UL1TR000128. CMN is supported by K01 AR062655. Funding Information: The MrOS Study is supported by the following institutes under the National Institutes of Health (NIH): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Center for Advancing Translational Sciences (NCATS), and NIH roadmap for Medical Research under the following grant numbers: U01AR45580, U01AR45614, U01AR45632, U01AR 45647, U01AR45654, U01AR45583, U01AG18197, U01AG027810, and UL1RR024140, P50 AR063043, and endowment to the Center of Musculoskeletal health, UC Davis. The proteomics measurements were supported by the National Institutes of Health (NIH) NIGMS Grant P41 GM103493 (RDS) and were performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy (DOE) national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is operated by Battelle for the DOE under Contract DE-AC05-76RL0 1830. Proteome data analysis was further supported by the preceding grant as well as NIH/NCATS grant UL1TR000128. CMN is supported by K01 AR062655. Publisher Copyright: {\textcopyright} 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.",
year = "2018",
month = apr,
doi = "10.1111/acel.12717",
language = "English (US)",
volume = "17",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "2",
}