# Role of Estrogen Related Receptors in Age Related Kidney Disease

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2024 · $754,233

## Abstract

Life-long caloric restriction (CR) prevents age-related decline in kidney health, including impaired mitochondrial
function, lipid accumulation, and inflammation. We determined that renal expression of the nuclear hormone
receptors the estrogen related receptors (ERRs) ERRα, ERRβ, and ERRγ decreases with age, and that CR
prevents this decrease. We found that treatment of 22-month-old mice with a pan ERR agonist upregulates the
renal expression of ERRα and ERRγ, and reverses the increase in urinary albumin excretion, the impaired
mitochondrial function, and the increase in inflammation. However, knowledge gaps remain, including 1) the
podocyte and tubule specific effects of ERRα or ERRγ, and if beneficial effects of ERRs on age-related kidney
disease depend on 2) alterations in kidney lipid composition and 3) proinflammatory immune cells.
Hypothesis: We hypothesize that ERRs play an important role in modulating age-related kidney disease. We
propose that: (1) decreased expression of ERRα or ERRγ accelerates age-related kidney diseases, whereas
increased expression of ERRα or ERRγ slows age-related kidney disease (SA1); (2) ERRs modulate age-related
kidney disease by inhibiting the increased synthesis and accumulation of ceramides and glycosphingolipids
(SA2); (3) ERRs modulate age-related kidney disease by inhibiting proinflammatory immune cells (SA3).
In SPECIFIC AIM 1, we will test the hypothesis that inducible decreased expression of ERRα or ERRγ in the
podocytes or the tubules accelerates, whereas inducible increased expression of ERRα or ERRγ in the
podocytes or tubules slows age-related kidney disease.
In SPECIFIC AIM 2, we will test the hypothesis that ERRs modulate age-related kidney disease by inhibiting
the increased synthesis and accumulation of ceramides and glycosphingolipids.
In SPECIFIC AIM 3, we will test the hypothesis that ERRs modulate age-related kidney disease by inhibiting
inflammatory immune cells.

## Key facts

- **NIH application ID:** 10981642
- **Project number:** 2R01DK127830-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** MOSHE LEVI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $754,233
- **Award type:** 2
- **Project period:** 2020-12-21 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981642

## Citation

> US National Institutes of Health, RePORTER application 10981642, Role of Estrogen Related Receptors in Age Related Kidney Disease (2R01DK127830-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10981642. Licensed CC0.

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