The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

Advancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate gland including benign prostatic hyperplasia (BPH) and prostate carcinoma. The prostate is comprised of a functional secretory epithelium, a basal epithelium, and a supporting stroma comprised of structural elements, and a spectrum of cell types that includes smooth muscle cells, fibroblasts, and inflammatory cells. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stroma could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate microenvironment that could influence pathology.We quantitated transcript levels in microdissected glandular-adjacent stroma from young (age 4 months) and old (age 20-24 months) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding proteins associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/oxidative stress (e.g., Apod, Serpinb5) and other paracrine-acting effects (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age-associated declines. By histology, immunofluorescence, and electron microscopy we determined that the collagen matrix is abundant and disorganized, smooth muscle cell orientation is disordered, and inflammatory infiltrates are significantly increased, and are comprised of macrophages, T cells and, to a lesser extent, B cells.These findings demonstrate that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate

Prenatal and pubertal testosterone exposure imprint permanent modifications in the prostate that predispose to the development of lesions in old Mongolian gerbils

The prostate is an accessory sex gland that develops under precise androgenic control. It is known that hormonal imbalance may disrupt its development predisposing this gland to develop diseases during aging. Although the hypothesis regarding earlier origins of prostate diseases was proposed many years ago, the mechanisms underlying this complex phenomenon are poorly understood. Therefore, the aim of this study was to evaluate the prostates of old male gerbils exposed to testosterone during intrauterine and postnatal life using morphological, biometrical, stereological, Kariometric, immunohistochemical, and immunofluorescence analyses. Our findings demonstrate that prenatal and pubertal exposure to testosterone increases the susceptibility to the development of prostate diseases during aging. The presence of a more proliferative gland associated with foci of adenomatous hyperplasia in animals exposed to testosterone during the prenatal and pubertal phase show that the utero life and the pubertal period are important phases for prostatic morphophysiology establishment, which is a determinant for the health of the gland during aging. Therefore, these findings reinforce the idea that prostate disease may result from hormonal disruptions in early events during prostate development, which imprint permanently on the gland predisposing it to develop lesions in later stages of life