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.

Public Health Relevance

Public Relevance The loss of normal voiding ability known as Detrusor Underactivity is a common cause for urinary symptoms including incontinence in later life. Considering DU as a disease of the bladder muscle has yielded no corrective therapy. We propose an innovative approach to Detrusor Underactivity, as the result of exaggerated normal changes of aging contributing to loss of resilience. Using novel methodologies and on-site collaborations possible only within our institution, we will discover specific factors that contribute to a loss of adaptive capabilities in later life which ultimate result in voiding deficiencies characterized by Detrusor Underactivity. These discoveries will re-define evaluative and therapeutic approaches to this difficult disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG058814-01A1
Application #
9737078
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kerr, Candace L
Project Start
2019-05-15
Project End
2024-01-31
Budget Start
2019-05-15
Budget End
2020-01-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Surgery
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030