Aging-Related Mitochondrial Dysfunction Is Associated With Fibrosis in Benign Prostatic Hyperplasia

Area of Science:

• Urology
• Gerontology
• Mitochondrial Biology

Background:

• Aging is the primary risk factor for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH).
• Pharmacotherapy for LUTS/BPH can fail due to pathological features like fibrosis and inflammation.
• The role of mitochondrial dysfunction, a hallmark of aging, in BPH pathology is largely unknown.

Purpose of the Study:

• To investigate the impact of mitochondrial dysfunction on the pathological features of BPH.
• To explore the potential of oleic acid (OA) as a therapeutic agent for LUTS/BPH.

Main Methods:

• Analysis of gene array data and immunohistochemistry for mitochondrial proteins in human prostate tissue.
• In vitro studies examining complex I inhibition effects on prostatic cells using qPCR, immunocytochemistry, and Seahorse assays.
• In vivo studies with aged mice treated with OA to assess urinary function and prostatic NDUFS3 expression.

Main Results:

• BPH tissues showed altered mitochondrial function and fibrosis genes, with decreased key mitochondrial proteins (e.g., NDUFS3).
• Complex I inhibition in cells reduced respiration, altered NDUFS3, and increased collagen deposition; OA treatment ameliorated these effects.
• OA-treated aged mice exhibited improved voiding function and increased prostatic NDUFS3 levels.

Conclusions:

• Complex I dysfunction may contribute to fibrosis and urinary dysfunction in aged mice.
• Oleic acid (OA) shows potential as a mitochondrial modulator for LUTS/BPH by partially bypassing complex I inhibition.
• This study identifies a novel cellular target for managing LUTS/BPH.