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Aging-Related Mitochondrial Dysfunction Is Associated With Fibrosis in Benign Prostatic Hyperplasia.
- Source :
-
The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2024 Jun 01; Vol. 79 (6). - Publication Year :
- 2024
-
Abstract
- Background: Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Although LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (eg, prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging; however, its impact on the pathological features of BPH remains unknown.<br />Methods: Publicly available gene array data were analyzed. Immunohistochemistry examined mitochondrial proteins in the human prostate. The effect of complex I inhibition (rotenone) on a prostatic cell line was examined using quantitative polymerase chain reaction, immunocytochemistry, and Seahorse assays. Oleic acid (OA) was tested as a bypass of complex I inhibition. Aged mice were treated with OA to examine its effects on urinary dysfunction. Voiding was assessed longitudinally, and a critical complex I protein measured.<br />Results: Mitochondrial function and fibrosis genes were altered in BPH. Essential mitochondrial proteins (ie, voltage-dependent anion channels 1 and 2, PTEN-induced kinase 1, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [NDUFS3]) were significantly (pā <ā .05) decreased in BPH. Complex I inhibition in cultured cells resulted in decreased respiration, altered NDUFS3 expression, increased collagen deposition, and gene expression. OA ameliorated these effects. OA-treated aged mice had significantly (pā <ā .05) improved voiding function and higher prostatic NDUFS3 expression.<br />Conclusions: Complex I dysfunction is a potential contributor to fibrosis and lower urinary tract dysfunction in aged mice. OA partially bypasses complex I inhibition and therefore should be further investigated as a mitochondrial modulator for treatment of LUTS/BPH. Hypotheses generated in this investigation offer a heretofore unexplored cellular target of interest for the management of LUTS/BPH.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Male
Animals
Mice
Humans
Mice, Inbred C57BL
Lower Urinary Tract Symptoms etiology
Lower Urinary Tract Symptoms metabolism
Lower Urinary Tract Symptoms physiopathology
Prostate pathology
Prostate metabolism
Electron Transport Complex I metabolism
Prostatic Hyperplasia metabolism
Prostatic Hyperplasia pathology
Prostatic Hyperplasia complications
Aging
Fibrosis
Mitochondria metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1758-535X
- Volume :
- 79
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The journals of gerontology. Series A, Biological sciences and medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 37738211
- Full Text :
- https://doi.org/10.1093/gerona/glad222