# Kidney Aging Impairs Progenitor and Endocrine Function

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $636,812

## Abstract

Project Summary and Abstract
Because the US population is living longer, the impact of advanced age on the kidney is highly clinically
relevant. Kidney disease outcomes are worse in the older versus younger patient population s and the elderly
comprise the largest group to initiate dialysis annually in the US. Recent attention in the aged kidney has been
given to cells of renin lineage because of their two essential functions: their endocrine function of producing the
body's supply of renin, and their adult progenitor function as facultative stem cells that transdifferentiate into
cell fates that they partially or fully replace, including podocytes. The scope of the problem is that in addition to
a decrease in total CoRL density in the aged kidney, both functions are also impaired with advancing age.
From the standpoint of glomerular diseases typified by podocyte depletion, reduced CoRL progenitor function
limits podocyte regeneration, and therefore repair in the aged kidney. We reported that aged CoRL undergo
senescence, apoptosis, and DNA damage, with an increase in complement components and inflammatory
cytokines, consistent with a chronic low-grade inflammatory state. Aged CoRL mitochondria have lower
biogenesis and energy, but increased reactive oxygen species accumulation. The knowledge gap is identifying
the mechanisms that cause these changes to CoRL in aged kidneys. Importantly, our data shows that
superimposed glomerular disease compounds the aging phenotype as follows: when podocytes are depleted
in young mice in experimental FSGS, the changes to the transcriptome in young CoRL are very similar to the
changes in CoRL in the healthy aged kidney without disease. We propose that changes to CoRL in glomerular
disease recapitulates and superimposes changes to CoRL in aged kidneys, and that this compounding effect
worsens disease outcomes in aged populations. The unmet need is targeting the mechanisms that impair
CoRL function in the aged kidney with disease, with the ultimate goal to minimize further injury to the aged
kidney. To achieve this, the following specific aims are proposed: (1) Test the hypothesis that senescence
impairs the facultative stem cell function of cells of renin lineage (CoRL) during aging. (2) Test the hypothesis
that chronic inflammation reduces the endocrine phenotype and function of aged cells of renin lineage. (3) Test
the hypothesis that mitochondrial changes in the aged kidney lowers the number of cells of renin lineage.
The significance of these studies includes uncovering, for the first time, potential mechanisms whereby age
impairs the CoRL endocrine phenotype and function, reduces CoRL progenitor function and lowers CoRL
density. In doing so, we will identify targets to modify in disease states in the aged kidney that maintain the
CoRL phenotype and enhance their functions. Innovations include identifying changes to a kidney cell (cells of
renin lineage) following injury to another kidney cell (podocyte loss...

## Key facts

- **NIH application ID:** 9860903
- **Project number:** 1R01DK123031-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Stuart James Shankland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $636,812
- **Award type:** 1
- **Project period:** 2020-02-11 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9860903

## Citation

> US National Institutes of Health, RePORTER application 9860903, Kidney Aging Impairs Progenitor and Endocrine Function (1R01DK123031-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9860903. Licensed CC0.

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