Sensitivity of urethral flow-evoked voiding reflexes decline with age in the rat: insights into age-related underactive bladder

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help in the development of new treatments by identifying mechanistic targets. In this work, we studied the relationship between age and systems-level function of the LUT and tested the hypothesis that aging is related to weakening of reflexes that control voiding. Three groups of anesthetized female rats, young (4-7 mo old), mature (11-14 mo old), and old (18-24 mo old), were used to quantify the effect of aging on LUT reflexes. A double-lumen catheter enabled us to control the bladder volume and urethral flow rate independently, under quasi-isovolumetric bladder conditions. We systematically investigated the reflex bladder contractions evoked by combinations of rates of urethral infusion and bladder fill volumes as a function of age. Urethral infusion with the same flow rate evoked bladder contractions (via the augmenting reflex) in old animals less often than in younger animals. Furthermore, old animals needed more fluid in their bladders (relative to their bladder capacity) before urethra flow-evoked bladder contractions could be triggered at all, suggesting a delay in the switch of the LUT to "voiding mode." Old rats also showed longer and weaker bladder contractions than young or mature rats. Taken together, this suggests there is an age-related functional weakening and loss of sensitivity in LUT reflexes, which may contribute to age-related UAB symptoms.