# Epigenetic Age Acceleration and Psychoneurological Symptoms in Sickle Cell Disease

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $241,500

## Abstract

PROJECT SUMMARY
Individuals with sickle cell disease (SCD) experience deleterious psychoneurological symptoms, such as pain,
sleep disturbances, depressive symptoms, and cognitive impairment. Among these symptoms, there is notable
interindividual variability. Few studies have sought to examine why some individuals experience worse
psychoneurological symptoms than others. Identifying biological factors, such as epigenetic mechanisms that
influence the variability of symptom experiences in SCD, can help inform the development of risk assessment
tools and interventions that promote health maintenance, quality of life, and reduce health disparities in this
population. Recent evidence has converged to suggest a person's epigenetic age may be associated with
psychoneurological symptom experiences in SCD. Epigenetic age is calculated by assessing DNA methylation
patterns at numerous CpG loci that account for the pace of cellular aging or declining tissue function.
Premature epigenetic age acceleration putatively involves many physiologic processes, including increased
inflammation, oxidative stress, and mitochondrial dysfunction. Associations with epigenetic age acceleration
and psychoneurological symptom experiences in other chronic disease populations has recently been
identified. However, whether epigenetic age acceleration occurs and if it is associated with these symptoms in
individuals with SCD remains unknown. The specific aims of this cross-sectional study are to 1) characterize
epigenetic aging DNA methylation patterns and determine presence of epigenetic age acceleration and 2)
identify associations between epigenetic age acceleration and psychoneurological symptoms (pain, sleep
disturbances, depressive symptoms, and cognitive function) in adults with SCD. DNA samples and patient-
reported outcome data already collected at Duke University as part of the Sickle Cell Disease Consortium
Research Registry (n=92) will be used in this study. DNA methylation data will be generated from the extracted
DNA of blood specimens and used to calculate epigenetic age. Because different epigenetic clocks provide
different measures and characteristics of epigenetic aging, epigenetic age acceleration will be calculated using
three epigenetic clocks (Horvath, Hannum, and Levine). We will also examine whether the calculations from
each of the clocks are correlated in the sample. Patient-reported data for each symptom of interest existing in
the SCDIC Registry will be used to determine associations with epigenetic age acceleration for each of the
epigenetic clocks. This “high risk, high return” study may provide novel insight into epigenetic aging biomarkers
associated with symptom development and health outcomes in people with SCD, an underrepresented
population. The data generated is essential for designing a rigorous and adequately powered R01 study to
understand the interactions of multiple level factors (e.g., epigenetic age acceleration, social determinants s...

## Key facts

- **NIH application ID:** 10449461
- **Project number:** 1R21NR020017-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** ALLISON E ASHLEY-KOCH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $241,500
- **Award type:** 1
- **Project period:** 2022-03-18 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449461

## Citation

> US National Institutes of Health, RePORTER application 10449461, Epigenetic Age Acceleration and Psychoneurological Symptoms in Sickle Cell Disease (1R21NR020017-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449461. Licensed CC0.

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