# Reciprocal Modulation of the Microbiome and Cellular Senescence in Metabolic Dysfunction

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2024 · $42,531

## Abstract

Abstract
Age dependent microbial dysbiosis is now considered to be a hallmark of aging. Understanding
the mechanisms by which the gut microbiome modulates aging phenotypes will yield new
avenues for the treatment and prevention of age-related disease. Our work has shown that
high-fat diet (HFD) and intermittent fasting (IF) diet generate distinct gut microbiomes, and have
contrasting-effects on cellular senescence. One central idea of the parent R01 grant is that diet
dependent changes in gut microbiome composition modulate cellular senescence. However, the
parent grant did not propose any molecular mechanism by which the gut microbiome may
impact senescence. This diversity grant proposes a mechanistic study that tests a novel
hypothesis that the microbiomes generated by HFD and IF differentially affect gut barrier
function, resulting in the translocation of Molecular Associated Molecular Patterns (MAMPs) with
opposing effects on senescence and macrophage function in Visceral Adipose Tissue (VAT).
Aim 1 will investigate the effect of the microbiomes produced by IF and HFD on gut barrier
integrity and characterize the microbiota that translocate into VAT. Single cell RNAseq will be
done to reveal how microbiome composition impacts polarization of the various types of
macrophages in visceral fat. Aim 2 will employ a combination of in-vivo, and in-vitro assays to
directly study how translocated MAMPs affect preadipocyte, adipocytes and macrophages, with
regard to senescence and macrophage function at the molecular level. This supplement
proposal provides the candidate with comprehensive cross-disciplinary training in the fields of
immunology, microbiome, and aging biology. This supplement will prepare the candidate to
successfully undertake and complete cutting-edge research as he develops his career as
geriatric immunologist.

## Key facts

- **NIH application ID:** 10838149
- **Project number:** 3R01AG068860-04S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Ming Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,531
- **Award type:** 3
- **Project period:** 2020-09-10 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838149

## Citation

> US National Institutes of Health, RePORTER application 10838149, Reciprocal Modulation of the Microbiome and Cellular Senescence in Metabolic Dysfunction (3R01AG068860-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10838149. Licensed CC0.

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