Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

Prior work documented that surgical removal of approximately 70% of the bladder (subtotal cystectomy) in 12-week-old female rats induced complete functional regeneration of the bladder within 8 weeks. To determine whether animal age affects bladder regeneration, female F344 rats aged 12 weeks (young) and 12 months (old) underwent subtotal cystectomy, and then when evaluated from 1 to 26 weeks after subtotal cystectomy. Af 26 weeks after subtotal cystectomy, bladder capacity in young animals was indistinguishable from that in age-matched controls, but bladder capacity in old animals was approximately 56% of that in age-matched controls. There was no detectable difference in residual volume among treatment groups, but the diminished regeneration in old animals was associated with a corresponding increase in the ratio of residual volume to micturition volume. The majority of old animals exhibited evidence of chronic kidney damage after subtotal cystectomy. Maximal contraction of bladder strips to electric field stimulation, as well as activation with carbachol, phenylephrine, and KCI, were lower in old than in young animals at 26 weeks after subtotal cystectomy. Immunostaining with proliferating cell nuclear antigen and Von Willebrand factor revealed delayed and/or diminished proliferative and angiogenic responses, respectively, in old animals. These results confirm prior work and suggest that multiple mechanisms may contribute to an age-related decline in regenerative capacity of the bladder.
Published in the American Journal of Pathology, v183 n5 p1585-1595, November 2013.