Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium
Purpose Lower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits s...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Continence Society
2022-06-01
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| Series: | International Neurourology Journal |
| Subjects: | |
| Online Access: | http://einj.org/upload/pdf/inj-2142224-112.pdf |
| _version_ | 1811325883277901824 |
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| author | Mathijs M. de Rijk Amanda Wolf-Johnston Aura F. Kullmann Stephanie Taiclet Anthony J. Kanai Sruti Shiva Lori A. Birder |
| author_facet | Mathijs M. de Rijk Amanda Wolf-Johnston Aura F. Kullmann Stephanie Taiclet Anthony J. Kanai Sruti Shiva Lori A. Birder |
| author_sort | Mathijs M. de Rijk |
| collection | DOAJ |
| description | Purpose Lower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits signaling properties via the release of mediators within the bladder wall that affect bladder functioning. Aging is associated with detrimental changes in cellular health, in part by increasing oxidative stress in the bladder mucosa, and more specifically the urothelium. This, in turn, may impact urothelial mitochondrial health and bioenergetics. Methods We collected mucosal tissue samples from both young (3–4 months old) and aged (25–30 months old) rats. Tissue was evaluated for p21-Arc, nitrotyrosine, and cytochrome C expression by western immunoblotting. Urothelial cells were cultured for single-cell imaging to analyze basal levels of reactive oxygen species and the mitochondrial membrane potential. Mitochondrial bioenergetics and cellular respiration were investigated by the Seahorse assay, and measurements of adenosine triphosphate release were made using the luciferin-luciferase assay. Results Aging was associated with a significant increase in biomarkers of cellular senescence, oxidative stress, and basal levels of reactive oxygen species. The mitochondrial membrane potential was significantly lower in urothelial cell cultures from aged animals, and cultures from aged animals showed a significant decrease in mitochondrial bioenergetics. Conclusions Aging-related increases in oxidative stress and excessive reactive oxygen species may be contributing factors underlying lower urinary tract symptoms in older adults. The mechanisms outlined in this study could be utilized to identify novel pharmaceutical targets to improve aging-associated bladder dysfunction. |
| first_indexed | 2024-04-13T14:41:18Z |
| format | Article |
| id | doaj.art-2903b18874874b06ab8c3e5f8e1687dd |
| institution | Directory Open Access Journal |
| issn | 2093-4777 2093-6931 |
| language | English |
| last_indexed | 2024-04-13T14:41:18Z |
| publishDate | 2022-06-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj.art-2903b18874874b06ab8c3e5f8e1687dd2022-12-22T02:42:53ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312022-06-0126211111810.5213/inj.2142224.1121001Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder UrotheliumMathijs M. de Rijk0Amanda Wolf-Johnston1Aura F. Kullmann2Stephanie Taiclet3Anthony J. Kanai4Sruti Shiva5Lori A. Birder6 Department of Urology, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAPurpose Lower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits signaling properties via the release of mediators within the bladder wall that affect bladder functioning. Aging is associated with detrimental changes in cellular health, in part by increasing oxidative stress in the bladder mucosa, and more specifically the urothelium. This, in turn, may impact urothelial mitochondrial health and bioenergetics. Methods We collected mucosal tissue samples from both young (3–4 months old) and aged (25–30 months old) rats. Tissue was evaluated for p21-Arc, nitrotyrosine, and cytochrome C expression by western immunoblotting. Urothelial cells were cultured for single-cell imaging to analyze basal levels of reactive oxygen species and the mitochondrial membrane potential. Mitochondrial bioenergetics and cellular respiration were investigated by the Seahorse assay, and measurements of adenosine triphosphate release were made using the luciferin-luciferase assay. Results Aging was associated with a significant increase in biomarkers of cellular senescence, oxidative stress, and basal levels of reactive oxygen species. The mitochondrial membrane potential was significantly lower in urothelial cell cultures from aged animals, and cultures from aged animals showed a significant decrease in mitochondrial bioenergetics. Conclusions Aging-related increases in oxidative stress and excessive reactive oxygen species may be contributing factors underlying lower urinary tract symptoms in older adults. The mechanisms outlined in this study could be utilized to identify novel pharmaceutical targets to improve aging-associated bladder dysfunction.http://einj.org/upload/pdf/inj-2142224-112.pdflower urinary tract symptomsurotheliumagingoxidative stressmitochondria |
| spellingShingle | Mathijs M. de Rijk Amanda Wolf-Johnston Aura F. Kullmann Stephanie Taiclet Anthony J. Kanai Sruti Shiva Lori A. Birder Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium International Neurourology Journal lower urinary tract symptoms urothelium aging oxidative stress mitochondria |
| title | Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium |
| title_full | Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium |
| title_fullStr | Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium |
| title_full_unstemmed | Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium |
| title_short | Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium |
| title_sort | aging associated changes in oxidative stress negatively impacts the urinary bladder urothelium |
| topic | lower urinary tract symptoms urothelium aging oxidative stress mitochondria |
| url | http://einj.org/upload/pdf/inj-2142224-112.pdf |
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