# Longitudinal Neurometabolic Outcomes of Traumatic Stress-Related Accelerated Cellular Aging

> **NIH NIH RF1** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $1,694,033

## Abstract

Early onset of age-related diseases, such as cardiometabolic disorders, inflammatory syndromes, and
neurodegenerative conditions, exact a large personal, economic, and societal toll and lead to shortened
healthspan and lifespan. Traumatic stress (trauma-related psychiatric symptoms) and genetic factors increase
the risk for an acceleration in the underlying pace of biological aging, as indicated by changes in peripheral
DNA methylation patterns (e.g., estimates of “epigenetic age”), increased inflammation, and metabolic
pathology. Alterations in these processes may hold predictive value for subsequent brain health. The aims of
this project are to examine traumatic stress-related accelerated aging in the periphery as an early predictor of
alterations in the neurochemistry of the brain and in neurocognitive performance over time. The study will also
examine genetic factors that may accentuate these associations. This project will build on two waves of
existing data, which include genotypes, psychological and neuropsychological assessments, and banked
plasma samples, by recruiting 160 participants in late middle age/early old age (all of whom have trauma
exposure and symptoms of traumatic stress) to return for a third assessment that is 5-15 years after baseline.
Participants will undergo cutting-edge magnetic resonance spectroscopy to asses for alterations in prefrontal
neurometabolites (including those relevant to neuroinflammation and neuronal viability, such as myo-inositol
and n-acetyl aspartate, respectively) and to examine neurocognitive performance, including assessment of
mild cognitive impairment. Banked DNA and plasma samples from the initial two time points, and new
peripheral samples from the third time point will be used to examine biomarkers that predict subsequent brain
health. The study will obtain measures of inflammation (e.g., cytokines) and neuropathology (e.g., amyloid
beta and total tau) using state-of-the-art Simoa® technology which yields extremely sensitive and precise
estimates of each analyte. Epigenome-wide DNA methylation will be obtained to examine accelerated
epigenetic age (i.e., when estimates of cellular age from established DNA methylation algorithms exceed
chronological age). Using longitudinal path analyses across the three time points of data, the study will
examine peripheral biomarkers (accelerated epigenetic age, inflammation, metabolic- and neuro-pathology) as
mediators of the association between prior traumatic stress and subsequent neural health. The study will
examine genetic variables, such as genome-wide risk scores for Alzheimer’s disease, cardiometabolic
pathology, and inflammation as well as genotypes relevant to dementia (i.e., in apolipoprotein or APOE) that
may moderate these associations. Ultimately, the study will identify early, peripheral prognostic markers of
subsequent accelerated aging in the brain, delineate the subpopulations at greatest risk by virtue of
psychiatric, genetic, and periph...

## Key facts

- **NIH application ID:** 10031095
- **Project number:** 1RF1AG068121-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** ERIKA J WOLF
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,694,033
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031095

## Citation

> US National Institutes of Health, RePORTER application 10031095, Longitudinal Neurometabolic Outcomes of Traumatic Stress-Related Accelerated Cellular Aging (1RF1AG068121-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10031095. Licensed CC0.

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