INTRODUCTION: Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients. METHODS: Single time point urine specimens were obtained from 140 OAB patients in the age range of 25-90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients. RESULTS: In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112-0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort. CONCLUSIONS: Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients.
INTRODUCTION: Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OABpatients. METHODS: Single time point urine specimens were obtained from 140 OABpatients in the age range of 25-90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OABpatients. RESULTS: In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OABpatients [Pearson r = 0.274; 95 %CI (0.112-0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OABpatients, and the remaining chemokines were undetectable in nearly two-third of OABpatients included in our cohort. CONCLUSIONS: Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OABpatients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OABpatients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OABpatients.
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