Accelerated Aging in Gulf War Illness: Phenotypes, Epigenetic Biomarkers, and Associations with Gulf War Exposures
Abstract
Objectives and Rationale: Our objective is to test the hypothesis that Veterans with Gulf War Illness (GWI) are aging faster than their peers without GWI and to understand whether individual-level susceptibility to toxic exposures affects this process. Prior research shows that, even 30 years after the war, Gulf War Veterans disproportionately report a host of co-occurring symptoms (e.g., fatigue, pain, and cognitive problems). Our study aims to newly examine how genetic differences alter the relationship between toxic exposures and aging. Such differences in the health consequences of a toxic exposure based one’s genetic profile is known as epigenetics. If we find that the epigenetics of aging differs for those with and without GWI, then this epigenetic biomarker may be used to advance future research and treatment options for these Veterans. Applicability to FY22 TERP Program Goals and Topic Areas: Our study aligns with these TERP Program Goals: (1) Evaluate genetic and epigenetic mechanisms and potential long-term and/or heritable outcomes; (2) Identify risk factors/genetic predictors for various diseases/conditions that may occur as a result of toxic exposure; (3) Understand individual exposures and their links to individual disease outcomes; and (4) Identify behavioral factors smoking, substance abuse, etc., co-morbidities and pre-existing medical conditions that may impact exposure outcomes. Our study aligns with these Topic Areas: (1) GWI and its treatment; (2) Identify and validate objective biomarkers for the diagnosis and monitoring of GWI and its progression and/or for assessing treatment efficacy; (3) Other military service-Related toxic exposures in general, including prophylactic medications, pesticides, organophosphates, toxic industrial chemicals, materials, metals, and minerals; and (4) Evaluate long-term effects of military toxicant exposures in exposed human populations, including Veterans. Potential Clinical Benefits: Our findings will indicate whether any of the epigenetic age biomarkers are specific for GWI. If so, these biomarkers might be useful for evaluating treatments for reducing the epigenetic age acceleration. Our findings could rapidly be used by ongoing and planned research studies, including clinical trials and other research on treatment effects in GWI, potentially speeding research into treatments for Gulf War Veterans. Project Timeline: Our study will produce estimates of the association of epigenetic accelerated aging measures on clinically derived aging estimate, GWI case status, and GWI symptoms in year 1. In year 2, we will perform an association study of accelerated aging estimates on GW exposures and GWECB and test for an interaction with accelerated aging. In year 3, we will complete manuscripts and disseminate findings to a broad audience including the research community at large, clinical scholars, and Veterans. Likely Contributions to Advance Knowledge: Our study will test the GWI accelerated aging hypothesis and support development of hypotheses related to associations with toxic exposures. If we find that epigenetic estimates of accelerated aging by GWI status, GWI symptoms, and/or toxic exposures, then these associations can be retested in other samples of GW Veterans such as those identified in the TERP RFA and/or the VA Million Veteran Program, which includes over 100,000 GW-era Veterans. Impact on the Health and Well-Being of Service Members, Veterans, and/or Military Beneficiaries: The smooth process for implementation of promising epigenetic aging measures for GWI will have a multiplicity of benefits by providing a longitudinal biomarker of GWI for development of treatment and as outcomes in clinical trials of GWI treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310799
Entities
People
- Elizabeth Hauser
Organizations
- Duke University
- United States Army