Age-related endolysosome dysfunction in the rat urothelium

• DOI: 10.1371/journal.pone.0198817
• Publication Date: 2018-06-08T17:30:56Z
• Authors: Steven T. Truschel; Dennis R. Clayton; Jonathan M. Beckel; Jonathan G. Yabes; Yi Yao; Amanda Wolf-Johnston; Lori A. Birder; Gerard Apodaca
• Keywords: Senescence; Lipofuscin

Lysosomal dysfunction is associated with a number of age-related pathologies that affect all organ systems. While much research has focused on neurodegenerative diseases and aging-induced changes in neurons, less known about the impact aging lower urinary tract function. Our studies explored age-dependent content endo-lysosomal organelles (i.e., multivesicular bodies, lysosomes, product their fusion, endolysosomes) age-induced effects lysosomal degradation urothelium, epithelial tissue lines inner surface bladder, ureters, renal pelvis. When examined by transmission electron microscopy, urothelium from young adult rats (~3 months), mature (~12 aged (~26 months old) demonstrated progressive accumulation aberrantly large endolysosomes (up to 7μm diameter) contained undigested content, likely indicating impaired degradation. Stereological analysis confirmed occupied approximately 300% more volume than younger counterparts while no change was observed bodies or lysosomes. Consistent diminished endolysosomal degradation, we cathepsin B activity significantly decreased versus urothelial cell lysates as well live cells. Further, pH higher (pH 6.0 vs 4.6). results indicate there decline function during aging. How this contributes bladder elderly discussed.