# Role of HDAC7 in senescence-associated inflammation

> **NIH NIH F32** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2021 · $70,458

## Abstract

PROJECT SUMMARY
Cellular senescence is a hallmark of the aging process and contributes to chronic disease vulnerability.
Although senescence acts acutely as a tumor suppressor mechanism, chronically it also contributes to
inflammation in aged tissue through the senescence-associated secretory phenotype (SASP). Hence, removal
of senescent cells in vivo improves healthspan and lifespan, although pharmacological “senolytic” approaches
tend to have toxic side effects, likely limiting the utility of senolytics as tools to promote healthy aging. As
proof-of-concept for an alternative approach, suppression of SASP in vivo reduces chronic liver inflammation
and delays onset of hepatocellular carcinoma. Recently, we have shown that SASP is dependent on expulsion
of cytosolic chromatin fragments (CCF) from the nucleus into the cytoplasm of senescent cells. We have
recently linked mitochondrial dysfunction to CCF production through a retrograde mitonuclear signaling
pathway. This pathway is blocked by histone deacetylase inhibitors through an unknown mechanism.
Unexpectedly, we recently discovered the histone deacetylase HDAC7 localizes in the nucleus of senescent
cells, is required for CCF formation, and is sensitive to mitochondrial status. We hypothesize that HDAC7 is a
novel component of mitochondria-nucleus retrograde signaling in senescent cells. This proposal has two
Aims, to: 1) Determine the mitonuclear signaling role of HDAC7, 2) Determine the nuclear role of
HDAC7 in CCF formation. Elucidation of the mechanism of this signaling pathway is of interest to all
biologists but can also identify therapeutic targets for reduction of SASP. This approach can uncover
alternatives to senolytic drugs for treatment of age-associated disease and promote healthy aging.

## Key facts

- **NIH application ID:** 10241964
- **Project number:** 5F32AG066459-03
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Karl Nathan Miller
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2019-09-12 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241964

## Citation

> US National Institutes of Health, RePORTER application 10241964, Role of HDAC7 in senescence-associated inflammation (5F32AG066459-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241964. Licensed CC0.

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