Integrated Proteomic and Metabolomic Analyses Implicate Redox-Metabolic Pathways in PTSD-Associated Multisystem Disease and Accelerated Aging

Details

• Journal Article:
  Nature Communications
• Personal Author:
  Kuan, Pei-Fen ; Mann, Frank D. ; Yang, Xiaohua ; Kotov, Roman ; Clouston, Sean A. P. ; Ilkayeva, Olga ; Muehlbauer, Michael ; Newgard, Christopher B. ; Luft, Benjamin J.
• Description:
  Posttraumatic stress disorder (PTSD) is associated with increased risk of chronic disease and premature aging, yet underlying molecular mechanisms remain unclear. We performed plasma proteomics (SomaScan; 9404 proteins) and targeted metabolomics (145 metabolites) in 393 World Trade Center responders (232 with PTSD, 161 trauma-exposed controls). A total of 114 proteins and seven metabolites were differentially expressed in PTSD. Top proteins included NCAN, BCAN, NCAM1, and GDF15. Top metabolites included serotonin, lactate, glutamic acid, and cystathionine. Integrative analyses showed coordinated proteomic-metabolomic alterations, with widespread correlations linking metabolites involved in redox and amino acid metabolism to synaptic and oxidative stress-related proteins. Gene ontology enrichment identified neuronal plasticity, immune activation, extracellular matrix remodeling, and oxidative stress. Proteomic organ aging analyses revealed accelerated aging in the pancreas, lung, and at the organismal level in PTSD. These results reveal a redox-metabolic mechanism through which PTSD may drive multisystem aging and elevate disease risk. Description provided by NIOSH
• Subjects:
  • Occupational Health
  • Safety
  • September 11 Terrorist Attacks
  • Stress Disorders, Post-Traumatic
• Keywords:
  • Post-traumatic stress disorder
  • PTSD
  • Traumatic incident stress
  • World Trade Center
  • WTC
  • Protein biochemistry
  • Molecular biology
  • Oxidative stress
  • Aging
• ISSN:
  2041-1723
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Contract
• Genre:
  Journal Article
• Place as Subject:
  Atlanta Region OSHA ; New York ; New York City Region OSHA ; North Carolina
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  32 pdf pages
• NIOSHTIC Number:
  nn:20071830
• Citation:
  Nat Commun 2026 Jun; :Epub ahead of print
• Contact Point Address:
  Pei-Fen Kuan, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA
• Email:
  PeiFen.Kuan@stonybrook.edu
• Federal Fiscal Year:
  2026
• Performing Organization:
  State University of New York Stony Brook
• Peer Reviewed:
  True
• Start Date:
  2023/07/01
• End Date:
  2026/06/30
• Download URL:
  https://stacks.cdc.gov/view/cdc/260053/cdc_260053_DS1.pdf
• File Type:
  [PDF - 13.85 MB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:296aeac665ad3b0bf7b6335330afd784bd7584bd34d5ed81a2c7ac1f7afe0f554f7334214c4f254fbb92283ef2c9de38b2640d723d84f94d72dabd3f4ee60535