Role of Senolytics in Lower Urinary Tract Aging and Voiding Disorders

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Project Summary/Abstract Lower urinary tract symptoms (LUTS), including urinary incontinence, overactive and underactive bladder, affect over half of the elderly population and are detrimental to quality of life and independence. Current drug therapies are mostly palliative, suboptimally effective and readily abandoned by patients and prescribers due to undesirable side effects. Urinary control is a complex multi-component operation, with aging representing a major risk factor and potential biological driver of altered voiding and incontinence in older adults. Senescent cells are a cell type which accumulates in aging tissues, releasing a host of chemicals that can impair tissue function. We have found evidence of these cells in bladder tissue. Together with published studies targeting other tissues, this suggests that available drugs aimed at eliminating senescent cells could be the basis for new therapies for urinary disorders associated with aging. In this exploratory project, we will use our aging mouse model to confirm the presence of these cells and study the impact of maturation and aging on their presence in bladder tissues. We will also test the ability of senolytics, drugs that can remove these cells, to reduce senescent cell presence in bladders from old animals. Finally, we will test the ability to maintain or recover youthful bladder function in old age using senolytics using our established aging mouse cystometry model. Our findings will provide important directive and supportive data for future research into the mechanisms of senescent cell involvement with aging and associated dysfunction, and may contribute to new and more effective prevention and treatment for urinary disorders of later life.