Role of Senolytics in Lower Urinary Tract Aging and Voiding Disorders

Senolytics 在下尿路老化和排尿障碍中的作用

• 批准号: 9902307
• 负责人: GEORGE A KUCHEL
• 金额: $ 20.5万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902307
• 关键词: Address; Admission activity; Affect; Age; Aged, 80 and over; Aging; Anesthesia procedures; Animals; Attenuated; Behavior; Biological; Biological Aging; Biological Assay; Bladder; Bladder Control; Bladder Dysfunction; Bladder Tissue; Brain; Brain Stem; Brain-Derived Neurotrophic Factor; Cardiac; Categories; Cells; Chemicals; Clinical; Cognition; Communication; Complex; Control Groups; DNA Damage; Dasatinib; Data; Development; Disease; Drug Combinations; Drug Targeting; Elderly; Exploratory/Developmental Grant; Frequencies; Functional disorder; Funding; Future; Genomics; Geroscience; Goals; Growth; Growth Factor; High Prevalence; Immune; Impairment; Incontinence; Individual; Lead; Link; Lower urinary tract; Measures; Mental Depression; Messenger RNA; Metabolic dysfunction; Micturition Reflex; Modeling; Mus; Natural History; Nature; Nerve; Neuregulin 1; Neuronal Plasticity; Nocturia; Nursing Homes; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Physiological; Population; Prevention; Process; Publishing; Quality of life; Quercetin; Reproducibility; Risk Factors; Role; Science; Sensory; Signal Transduction; Smooth Muscle Myocytes; Stains; Stress; Symptoms; Syndrome; System; Technology; Testing; Therapeutic; Time; Tissues; Urethane; Urinary Incontinence; Urine; age group; age related; aged; awake; beta-Galactosidase; bone loss; cell type; density; experimental study; frailty; functional decline; lower urinary tract symptoms; mouse model; novel therapeutics; operation; palliative; prevent; resilience; response; senescence; sex; side effect; stressor; telomere; translational approach; treatment group; urinary

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.

项目总结/文摘