# Neurobiological Correlates of Accelerated Cellular Aging

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $157,500

## Abstract

Project Summary/Abstract
Epigenome-wide DNA methylation data can be combined via a weighted algorithm to index cellular age.
These “DNA methylation age” estimates can then be used to determine the extent to which an individual’s
cellular age is advanced compared to his or her chronological age (i.e., accelerated cellular aging). Various
environmental and behavioral factors, including trauma exposure, posttraumatic stress disorder, and poor
sleep, have been associated with advanced DNA methylation age. Advanced DNA methylation age, in turn,
has been linked to early onset of a number of adverse health conditions, including neurocognitive decline and
metabolic aberrations. Accelerated cellular aging may help to explain the association between trauma- and
stress-related psychiatric conditions and premature morbidity and mortality. However, the current state of the
science in this area is limited by an almost exclusive emphasis on blood-based markers. Until now, the field
has lacked systematic investigations of traumatic stress in association with advanced DNA methylation age in
brain tissue and overall, little is known about the neurobiological correlates of advanced DNA methylation age.
Specifically, no study has evaluated the gene expression correlates of advanced DNA methylation age in brain
tissue. This project aims to address this limitation by examining associations between trauma-related
psychiatric disorders (including posttraumatic stress disorder, depression, and alcohol-use disorders) and
cellular age in human postmortem prefrontal brain tissue and will also evaluate the gene expression correlates
of advanced DNA methylation age in the same tissue. The study will make use of an existing resource, the VA
National PTSD Brian Bank, including existing DNA methylation and phenotype data, and it will also generate
new expression data using the banked samples from 117 brains. We will explore associations between
advanced DNA methylation age and altered expression of inflammation, immune, oxidative stress, and
glucocorticoid-related genes. We will also test the novel hypothesis that advanced DNA methylation age is
related to chronobiological disruption as evidenced by alterations in expression of circadian clock-related
genes. The proposed study is expected to clarify the biological pathways that link traumatic stress and related
psychopathology to premature aging of the brain.

## Key facts

- **NIH application ID:** 9868879
- **Project number:** 5R21AG061367-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** ERIKA J WOLF
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,500
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868879

## Citation

> US National Institutes of Health, RePORTER application 9868879, Neurobiological Correlates of Accelerated Cellular Aging (5R21AG061367-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9868879. Licensed CC0.

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