# Impact of dysbiosis on the development of age-related inflammation

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $418,750

## Abstract

PROJECT SUMMARY
The “pillars of aging” hypothesis entails that chronic unresolved inflammation, coupled with metabolic
dysfunction and macromolecular damage are among the key mechanisms that impairs cellular renewal and
regenerative processes that contribute to aging and chronic diseases. Inflammation is a protective mechanism
that has evolved to protect against pathogens and tissue injury that enables a host to survive life-threatening
challenges by restoration of homeostasis. How then does a protective response like inflammation become
chronic, drive aging and serve as a trigger of chronic disease? In absence of overt infections in aging,
alterations in the gut microbiota (dysbiosis) or potential translocation of microbiota derived PAMPs to liver,
mesenteric and omental adipose tissue could contribute to the mechanism of age-related inflammation. In line
with this possibility, recent studies have demonstrated profound changes in the microbiome associated with
aging and suggest that the microbiome may play a causal role in certain aspects of inflammaging. We recently
discovered that aging is associated with formation of tertiary lymphoid structures, called Fat-associated
lymphoid clusters (FALCs), in the visceral adipose tissue. The FALCs, unlike lymph nodes are disorganized
non-encapsulated non-classical lymphoid tissues associated to adipocytes contain T cells, B cell and
macrophages. Moreover, we found that B cells expand with age in the FALCs and display a unique
transcriptional profile reminiscent of antigen-experienced B cells. Based on our original findings, the central
hypothesis of this application is that translocation of gut microbes to visceral adipose tissue results in FALC
formation and age-related inflammation leading to metabolic dysfunction. We will test the mechanism of how
preventing the translocation of microbiota protects against FALC formation and inflammaging.

## Key facts

- **NIH application ID:** 10695871
- **Project number:** 5R01AG068863-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VISHWA DEEP DIXIT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695871

## Citation

> US National Institutes of Health, RePORTER application 10695871, Impact of dysbiosis on the development of age-related inflammation (5R01AG068863-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10695871. Licensed CC0.

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