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Age-related endolysosome dysfunction in the rat urothelium
Steven T Truschel1, Dennis R Clayton1, Jonathan M Beckel2
1Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Plos One
|June 9, 2018
Summary
Aging impairs lysosomal function in the bladder lining (urothelium), leading to larger, dysfunctional endolysosomes and reduced degradation. This decline in urothelial endolysosomal function contributes to age-related bladder issues.
Area of Science:
- Cell Biology
- Gerontology
- Urology
Background:
- Lysosomal dysfunction is linked to age-related diseases across organ systems.
- Research on aging's impact on the lower urinary tract, specifically the urothelium, is limited compared to neurodegenerative diseases.
Purpose of the Study:
- To investigate age-dependent changes in endo-lysosomal organelles within the urothelium.
- To assess the effects of aging on lysosomal degradation capacity in the urothelium.
Main Methods:
- Transmission electron microscopy to examine urothelial organelles in rats of different ages (young, mature, aged).
- Stereological analysis to quantify organelle volume.
- Measurement of cathepsin B activity and endolysosomal pH in urothelial cell lysates and live cells.
Main Results:
- Aged urothelium showed a progressive accumulation of significantly larger endolysosomes containing undigested material.
- Aged endolysosomes occupied ~300% more volume compared to younger ones; no significant changes in multivesicular bodies or lysosomes.
- Cathepsin B activity was decreased, and endolysosomal pH was higher (pH 6.0 vs. 4.6) in aged urothelium, indicating impaired lysosomal degradation.
Conclusions:
- Aging leads to a progressive decline in urothelial endolysosomal function.
- Impaired lysosomal degradation in the urothelium may contribute to age-related lower urinary tract dysfunction.
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