Prostate enlargement and altered urinary function are part of the aging process

Abstract

Prostate disease incidence, both benign and malignant, directly correlates with age. Men under 40 years of age are rarely diagnosed with benign or malignant prostate disease, while 90% of men over the age of 80 have histological evidence of benign disease (benign prostatic hyperplasia; BPH). Although rodent models have been invaluable in the study of disease progression and treatment efficacy, the effect of age is often not considered. In examining aged (24-month-old) mice, we observed changes within the lower urinary tract that is typically associated with lower urinary tract dysfunction (LUTD) similar to models of BPH. In this study, we identify LUTD using functional testing as well as various imaging technologies. We also characterize the histological differences within the lower urinary tract between young (2-month-old) and aged mice including proliferation, stromal remodeling, and collagen deposition. Additionally, we examined serum steroid hormone levels, as steroid changes drive LUTD in mice and are known to change with age. We conclude that, with age, changes in prostate function, consistent with LUTD, are a consequence. Therapeutic targeting of endocrine and prostatic factors including smooth muscle function, prostate growth and fibrosis are likely to reestablish normal urinary function.

CD4+ T helper 17 cell response of aged mice promotes prostate cancer cell migration and invasion

“…Although the anatomical differences of the prostate lobe make changes in mice difficult to directly correlate with changes in humans, there are substantial similarities in embryological, cellular, and molecular biology features (approximately 95% identical with human genome). This result suggests that as mice age, there is a development of the prostate‐related disease that corresponds to human diseases, such as benign prostatic hyperplasia and prostate carcinoma, which are associated with aging 35‐38 . Our results also showed an increase in the mRNA levels of proinflammatory mediators IL‐1β, TNF‐α, and IL‐6 and proinflammatory Th17‐related cytokines (IL‐17A, IL‐17F, and IL‐22), and activated NF‐κB and ERK1/2 signaling compared to young mouse prostate tissues.…”

Factors Driving Unique Urination Phenotypes of Male and Female 9-week-old C57BL/6J Mice

“…We recently documented an aging-related voiding dysfunction between 2-month and 24-month-old male C57BL/6J mice. 19 Here, we honed in on urinary function in young adult (1.5 – 3.5-month-old) mice. We performed VSA on 6, 7, 8, 9, 10, 12, and 14-week old male C57BL/6J mice and all measured endpoints changed with age (Figure 3, Table 3).…”

“…18 Several studies demonstrate a clear influence of prostate pathologies on mouse urinary voiding behaviors. 19–22 Influence of the mouse prostate on baseline voiding function has not been specifically evaluated, in part because many methods to alter prostate mass also alter circulating testosterone concentrations.…”

Reproductive tract biology: Of mice and men

“…Other than humans, dogs are the only other species to spontaneously develop BPH. Recently, aged mice were found to have cellular, anatomical, and functional aspects of BPH (Liu et al, 2019). For decades, it was believed that mice would not make good models for BPH/ LUTD research because the anatomy of distinct prostatic lobes in mice is anatomically dissimilar to that of the human prostate.…”

“…As such, a similar anatomical/cellular impingement "mechanism" exists in both men and rodents. Moreover, this obstruction is associated with mouse urinary dysfunction (Liu et al, 2019;Nicholson et al, 2012Nicholson et al, , 2015Ricke et al, 2018). Thus, rodents have been successfully used to model BPH in humans.…”