# Epigenetics of HIV, Aging, and Sleep Deficiency

> **NIH NIH P30** · YALE UNIVERSITY · 2022 · $436,290

## Abstract

Project Summary/Abstract
Older people living with HIV (PLWH) are at high risk for multiple adverse geriatric outcomes, including
cognitive impairment. Cognitive impairment in older PLWH has been closely linked to CNS immune activation,
but the cellular mechanisms driving this abnormal CNS immune activity remain unknown, and the role of
epigenetic modifications in promoting CNS immune activation in PLWH has not been examined. Epigenetic
changes provide a potential link between HIV, sleep deficiency, and aging-induced CNS immune activation.
DNA methylation (DNAm), one of the main and best-characterized epigenetic modifications, is affected by
normal aging, by HIV infection, and by sleep deficiency, which is highly prevalent in PLWH. While DNAm
changes can occur anywhere in the genome, the epigenetic integrity of circadian clock genes has been
specifically tied to maintaining immune homoeostasis in the brain, and the epigenetic disruption of these genes
has been associated with neuroinflammation. Our preliminary studies in PLWH demonstrate that DNAm of
circardian clock genes within CNS-disease relevant monocytes is differentially altered in PLWH compared to
controls, suggesting that these epigenetic changes may contribute to CNS disease in older PLWH. For this
proposed administrative supplement to the Yale Pepper Center parent grant, we will measure epigenetic
changes in circadian clock genes in both peripheral blood and in cerebrospinal fluid (CSF) immune cells from
older PLWH and matched controls, using tissue already biobanked as part of the Yale HARC cohort study of
PLWH. In AIm 1, we will assess whether epigenetic changes in circadian-clock genes associate with soluble
CSF markers of CNS immune activation. In Aim 2, we will assess whether sleep deficiency associates with
epigenetic dysregulation of circadian clock genes, and with CNS immune activation in PLWH. This work will be
performed by a multidisciplinary team from the Yale Pepper Center and Weill Cornell, with diverse expertise in
aging, HIV neurology, epigenetics, sleep, and biostatistics. The results will inform future interventions to
improve sleep deficiency and prevent adverse neurocognitive and functional outcomes in older PLWH.

## Key facts

- **NIH application ID:** 10610023
- **Project number:** 3P30AG021342-20S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Thomas Michael Gill
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,290
- **Award type:** 3
- **Project period:** 2002-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10610023

## Citation

> US National Institutes of Health, RePORTER application 10610023, Epigenetics of HIV, Aging, and Sleep Deficiency (3P30AG021342-20S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10610023. Licensed CC0.

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