# Histone H4 Lysine16 Acetylation in Aging and Lung Fibrosis

> **NIH NIH R01** · EASTERN VIRGINIA MEDICAL SCHOOL · 2020 · $70,042

## Abstract

PROJECT SUMMARY
 Idiopathic pulmonary fibrosis (IPF) is an age related fatal disease with unknown etiology.
Its incidence increases with age, environmental effects is important. Epigenetic changes,
including DNA methylation and histone modifications, are major causes of age-related diseases.
Environmental stressors and aging contribute to histone modifications. Epigenetic modifications
are potentially reversible. We and others have established that epigenetic mechanisms
participate in the pathogenesis of IPF. Aging may potentiate the susceptibility to environmental
stress by modulating pro-fibrotic cellular phenotypes in IPF. However, studies of epigenetic
regulation, in particular histone modifications and their related cellular phenotypes in the aging
lung and in IPF are lacking.
 Chromatin structure, which is affected by histone modifications, is an important
determinant of the cell phenotype. The active histone mark H4K16Ac epigenetically regulates
gene expression. Our preliminary data demonstrated the dysregulation of this histone
modification in IPF fibroblasts. We hypothesize that age-related histone modifications, in
particular H4K16Ac, mediates fibrotic cell phenotype, promotes senescence and induced
apoptosis resistant lung fibroblasts that leads to persistent fibrosis in aging. Targeting this
histone modification will alter pro-fibrotic cell phenotypes and promote resolution of fibrosis. Our
specific aims are: (1) Determine mechanisms that regulate H4K16Ac in persistent lung fibrosis
associated with aging. (2) Determine the role of H4K16Ac in regulating pro-fibrotic phenotypes
in fibrotic lung fibroblasts. (3) Determine the efficacy of targeting H416Ac in an aging mice
model of persistent lung fibrosis. The proposed studies will define the role of age-related
histone modification H4K16Ac in the pathogenesis of IPF, and translate that knowledge to novel
therapeutic interventions for pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10934126
- **Project number:** 7R01AG050567-06
- **Recipient organization:** EASTERN VIRGINIA MEDICAL SCHOOL
- **Principal Investigator:** Yan Sanders
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,042
- **Award type:** 7
- **Project period:** 2023-09-23 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934126

## Citation

> US National Institutes of Health, RePORTER application 10934126, Histone H4 Lysine16 Acetylation in Aging and Lung Fibrosis (7R01AG050567-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10934126. Licensed CC0.

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