Abstract
Age-related changes in various tissues have been associated with the onset of a number of age-related diseases, including inflammation and cancer. Bladder cancer, for instance, is a disease that mainly afflicts middle-aged or elderly people and is mostly of urothelial origin. Although research on age-related changes of long-lived post-mitotic cells such as neurons is rapidly progressing, nothing is known about age-related changes in the urothelium of the urinary bladder, despite all the evidence confirming the important role of oxidative stress in urinary bladder pathology. The purpose of this study was thus to investigate the oxidative status and age-related changes in urothelial cells of the urinary bladder of young (2 months) and aging (20 months) mice by means of various methods. Our results demonstrated that healthy young urothelium possesses a powerful antioxidant defence system that functions as a strong defence barrier against reactive species. In contrast, urothelial cells of aging bladder show significantly decreased total antioxidant capacity and significantly increased levels of lipid peroxides (MDA) and iNOS, markers of oxidative stress. Our study demonstrates for the first time that ultrastructural alterations in mitochondria and accumulation of lipofuscin, known to be one of the aging pigments, can clearly be found in superficial urothelial cells of the urinary bladder in aging mice. Since the presence of lipofuscin in the urothelium has not yet been reported, we applied various methods to confirm our finding. Our results reveal changes in the oxidative status and structural alterations to superficial urothelial cells similar to those of other long-lived post-mitotic cells.
Highlights
The urothelium of the urinary bladder is a three layered epithelium covering the luminal side of the urinary bladder
It contains a low proportion of post-mitotic superficial cells, which are incapable of further proliferation
We demonstrated for the first time that superficial urothelial cells of aging bladder show changes in oxidative status and structural alterations that accumulate over time, similar to those of other long-lived post-mitotic cells in the aging process
Summary
The urothelium of the urinary bladder is a three layered epithelium covering the luminal side of the urinary bladder. Labelling indices are known to vary between 0.5% and 1%, cell cycle time is about one year and mitotic cells are mostly present in deeper layers and never in the superficial layer [1,2,3]. The urothelium contains a low proportion of cycling cells capable of resuming cell cycle progression when required. It contains a low proportion of post-mitotic superficial cells, which are incapable of further proliferation. It has been demonstrated that terminally differentiated superficial cells in murine urinary bladder have a lifespan of more than 200 days [2,4], which suggests that superficial cells may be subject to agerelated changes responsible for various urinary bladder disorders
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