# Epigenetic Age and Patient Outcomes after Severe Traumatic Brain Injury

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $786,785

## Abstract

ABSTRACT
Aging is a risk factor for many chronic conditions including Alzheimer’s disease (AD) and Alzheimer’s disease
related dementias (ADRD) and impacts patient outcomes after traumatic brain injury (TBI). Aging can be
chronologic aging (time since birth) or biological aging that may differ substantially from chronological age for
some individuals, putting them at increased risk (accelerated biological aging) or decreased risk (decelerated
biological aging) for age related conditions including AD and ADRD and poorer recovery from TBI. Epigenetic
age measured using DNA methylation and epigenetic clock computations is one way to quantify biological age.
Another risk factor besides age for ADRD is TBI particularly severe TBI. In our preliminary work we have
developed epigenetic clock based biological age and calculated epigenetic age acceleration from DNA
extracted from serial cerebrospinal fluid (CSF) samples during the acute phase following severe TBI. Our
preliminary work has implicated epigenetic clock based biological age and epigenetic age acceleration during
the acute phase post injury in patient outcomes at 6, 12, and 24 months after severe TBI. We also have
evidence that social deprivation may impact epigenetic age acceleration in patients who have suffered a
severe TBI. Additionally, DNA methylation of the BDNF gene from serial CSF samples could be a biomarker
for patient outcomes after severe TBI, but the role of this biomarker appears to differ depending on the age of
the patient. This project will expand these investigations in a larger cohort of well-characterized severely
injured individuals with severe TBI. Expected results include finding a link between accelerated epigenetic
aging and variation in patient outcomes up to 2 years after severe TBI and that social determinants of health
impact accelerated epigenetic aging in this patient population. Accelerated epigenetic aging could be a useful
biomarker for prognosticating about a patient’s acute and chronic outcomes as well as guiding and monitoring
treatment during the acute and chronic phases after TBI. Knowledge that accelerated epigenetic aging impacts
patient outcomes after severe TBI, and identifying what influences accelerated epigenetic aging in this
population, could also inform treatment developments. Harnessing this knowledge could be beneficial to
patients who have sustained a severe TBI. Knowing that TBI is a risk factor for AD/ADRD, caring for the
severely injured brain with evidence-based interventions could also help mitigate long term sequela after TBI
that includes mitigating risk for AD/ADRD.

## Key facts

- **NIH application ID:** 10878118
- **Project number:** 1R01AG082734-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yvette P Conley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $786,785
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878118

## Citation

> US National Institutes of Health, RePORTER application 10878118, Epigenetic Age and Patient Outcomes after Severe Traumatic Brain Injury (1R01AG082734-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10878118. Licensed CC0.

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