# Role of Histone Deacetylase 9 (HDAC9) in adipose tissue aging: mitochondrial function, oxidative stress and senescence

> **NIH NIH F30** · AUGUSTA UNIVERSITY · 2023 · $52,694

## Abstract

PROJECT SUMMARY
Adipose tissue is a major depot for senescent cell accumulation and sterile inflammation in aging. While adipose
tissue senescence in aging is causally linked to mitochondrial dysfunction and oxidative stress, the underlying
mechanisms are undefined. Here, we propose the novel hypothesis that histone deacetylase 9 (HDAC9), a class
II histone deacetylase, plays a key role in promoting adipose tissue senescence in aging by promoting
mitochondrial dysfunction. Our preliminary data demonstrate that HDAC9 expression is increased in adipose
tissues of aged mice and humans. Moreover, HDAC9 gene deletion improves adipose tissue mitochondrial
energy expenditure and reduces adipose stem cell (ASC) senescence in 1-year-old chow diet fed mice, while
protecting ASCs against senescence in vitro. Our hypothesis will be tested with two specific aims. Aim 1 will test
the hypothesis that increased HDAC9 expression in aged adipose tissues contributes to mitochondrial
dysfunction and oxidative stress by disrupting mitochondrial dynamics. Our preliminary data suggest that HDAC9
is strongly upregulated in the mature adipocytes of aged mice. Therefore, we will employ two novel mouse
models to test our hypothesis: adipocyte-specific HDAC9 knockout (A-KO; HDAC9flox/flox adiponectin-Cre) and
adipocyte-specific transgenic (A-Tg, HDAC9Tg-flox-STOP-flox adiponectin-Cre) mice. Primary ASCs will be cultured
and differentiated to mature adipocytes. Mitochondrial function and dynamics will be measured in adipose tissue
explants and mature adipocytes using the Seahorse analyzer, Western blot, immunofluorescence, transmission
electron microscopy and confocal imaging. Aim 2 will test the hypothesis that HDAC9 gene deletion represses
the development of adipose tissue senescence and promotes healthy adipose tissue aging, while overexpression
of HDAC9 accelerates adipose tissue aging and augments senescence. We will quantify senescent cell
accumulation in adipose tissue and metabolic health through glucose and insulin tolerance testing. ASC cultures
from global HDAC9 knockout mice will be used to assess susceptibility to UV-induced senescence. Additionally,
senescent cell accumulation in A-KO and A-Tg mice will be assessed by senescence-associated β-galactosidase
staining, qRT-PCR and Western blot. This project will allow me to acquire deep knowledge of mitochondrial
biology while developing new technical skills, including primary cell culture, tissue staining and imaging. Most
importantly, it will allow me to gain expertise in conducting rigorous, hypothesis-driven research, thus setting the
stage for a career as a physician-scientist. The project will be conducted under the mentorship of Dr. Neal
Weintraub and co-mentorship of Dr. Masuko Ushio-Fukai in the Vascular Biology Center at the Medical College
of Georgia at Augusta University, which has a rich history of successful pre- and post-doctoral training. We
anticipate that findings from this proposal will identify ...

## Key facts

- **NIH application ID:** 10707000
- **Project number:** 5F30AG074640-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Brandee Goo
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $52,694
- **Award type:** 5
- **Project period:** 2022-08-15 → 2025-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10707000

## Citation

> US National Institutes of Health, RePORTER application 10707000, Role of Histone Deacetylase 9 (HDAC9) in adipose tissue aging: mitochondrial function, oxidative stress and senescence (5F30AG074640-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10707000. Licensed CC0.

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