# Detrusor Underactivity as an HCN-mediated Failure of Resilience in Aging

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $575,955

## Abstract

ABSTRACT
Detrusor Underactivity (DU) is a voiding impairment due to insufficient bladder muscle effort to ensure timely
and efficient bladder emptying. As a disorder of volume management, DU is often associated with
incontinence and other urinary symptoms, especially in later life. Despite the term suggesting a bladder
muscle disorder, a key characteristic of DU is loss of sensitivity to bladder volume. Like DU, aging is also
associated with loss of volume sensitivity. Moreover, aging is characterized by increasing risk of failure to
adapt to biologic challenge, i.e. loss of resilience. We therefore propose that DU is not a detrusor disease,
rather it is a manifestation of the nonresilient end of the spectrum of bladder sensory changes of aging. In this
project we will investigate the role of a “pacemaker” ion channel in the age evolution of a control mechanism
critical to bladder volume sensitivity. We hypothesize that DU is associated with the more severe age-
associated changes. This knowledge will allow us to determine the control factors contributing to the loss of
successful, resilient aging and the resulting non-resilience manifested as DU. To accomplish these goals will
use our established mouse cystometry model to test urinary resilience and define a DU group separate from
age groups. Our research methods will include single cell genomic sequencing, electrophysiology,
molecular/cellular investigations, and correlative tissue-level experiments in order to address our objective. By
taking advantage of the uniquely available combined expertise within the UConn Center on Aging,
Neurosciences department, and on-site Jackson laboratory, we will address the goal of identifying DU
pathophysiology and contributing to an improved therapeutic model which recognizes DU as an adaptive
failure.

## Key facts

- **NIH application ID:** 10556327
- **Project number:** 5R01AG058814-05
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** GEORGE A KUCHEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $575,955
- **Award type:** 5
- **Project period:** 2019-05-15 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556327

## Citation

> US National Institutes of Health, RePORTER application 10556327, Detrusor Underactivity as an HCN-mediated Failure of Resilience in Aging (5R01AG058814-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10556327. Licensed CC0.

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