# Discovering mechanisms of tissue-resident immune aging

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $1,453,500

## Abstract

Project Summary
Persistent low-grade inflammation underlies the development of chronic diseases that are prevalent in the
elderly. Adipose tissue displays unique susceptibility to age-related inflammation. Even healthy individuals
accumulate visceral adiposity in older age, leading to increased systemic inflammation and reduced metabolic
health. A strong candidate source of inflammation in aged adipose tissue is the resident immune compartment.
Within every organ is a specialized repertoire of resident immune cells that is essential for tissue homeostasis
and stress adaptation. In adipose tissue, resident immune cells coordinate responses to fasting and cold, and
our prior work establishes that changes in adipose-resident immune cells impairs responses to both these
challenges in old mice. But the mechanisms that drive adipose-resident immune dysfunction throughout the
lifespan have remained elusive. This proposal will leverage new technological approaches to address this
outstanding question. Peripheral immune cells accumulate intracellular defects during aging, leading to poor
immune protection after vaccination or infection. Given that tissue-resident immune cells are seeded early in life
and maintained through self-renewal, we expect them to be especially sensitive to age-related regulatory
pressures. Importantly, immune cells are also sensitive to environmental cues, and extracellular cytokines and
nutrient availability strongly influence the recruitment and function of immune cells. Therefore, we hypothesize
that both immune cell-intrinsic and -extrinsic mechanisms cause dysregulation of the aging adipose-resident
immune compartment. We will use an inducible fate-mapping strategy, combined with intra-vascular labeling, to
study bonafide long-lived adipose-resident immune cells. We will use a viral vector-based proximity ligation
approach to discover age-dependent changes in adipose secreted proteins and test how they impact resident
immune cells. By comparing old and younger obese mice, we will isolate age-specific mechanisms of
inflammation and adipose tissue dysfunction. We will use these results to develop new strategies that protect
the aging adipose-resident immune compartment and prevent inflammation. Our methods overcome several
longstanding obstacles in aging science: (1) knowing the “age” of an immune cell, and (2) pinpointing known cell
sources of age-associated cytokines/secreted factors. With these new capabilities, our work stands to advance
aging science and enable discovery of new disease mechanisms affecting any organ system.

## Key facts

- **NIH application ID:** 10472369
- **Project number:** 1DP2AI175641-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Emily Lauren Goldberg
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,453,500
- **Award type:** 1
- **Project period:** 2022-09-08 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472369

## Citation

> US National Institutes of Health, RePORTER application 10472369, Discovering mechanisms of tissue-resident immune aging (1DP2AI175641-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10472369. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*