ABSTRACT
Lower urinary tract symptoms (LUTS) are a significant burden to aging men and are often as a result of benign
prostatic hyperplasia (BPH). While BPH/LUTS is not commonly fatal with proper medical intervention, it does
cause a significant reduction in quality of life for many men as they age. Furthermore, BPH/LUTS increases risk
of mortality and results in billions of dollars in healthcare costs annually. There is currently a subset of BPH/LUTS
patients that fail FDA-approved treatments (a-blockers, 5ARI), and these patients have been shown to have
increased prostatic fibrosis. There is no FDA-approved medication targeting fibrosis or the aging process in
BPH/LUTS, even though aging is the greatest risk factor. This proposal aims to develop a better understanding
about the role of aging, fibrosis, and mitochondrial dysfunction in BPH/LUTS. Mitochondrial dysfunction is a
hallmark of both aging and fibrosis and has not been thoroughly studied in relation to BPH/LUTS. Preliminary
data suggests that oxidative phosphorylation (OXPHOS) is a mitochondrial pathway contributing to cellular
dysfunction in BPH/LUTS. Aim 1 of this proposal intends to investigate the connection between OXPHOS
disruption and lower urinary tract dysfunction (LUTD) in a novel mouse model. Aim 2 of this proposal will
investigate the connection between OXPHOS disruption and pathways associated with fibrosis, using genetic
loss-of-function cell line models. Finally, Aim 3 will work to identify a new pathway of interest for treatment, using
oleic acid as a mitochondrial metabolism modulator. Collectively, these aims will improve our overall
understanding of the processes underlying BPH/LUTS, with a special focus on aging, mitochondrial dysfunction,
and fibrosis. This proposal hopes to provide translational outcomes that can eventually improve patient care and
treatment options.
