Preventive Effects of Long-Term Caloric Restriction on Aging Related In Vivo Bladder Dysfunction and Molecular Biological Changes in the Bladder and Dorsal Root Ganglia in Rats

Abstract

Purpose: We evaluated aging related bladder dysfunctions and biological changes in the bladder and dorsal root ganglia in rats. We also investigated whether long-term caloric restriction may have preventive effects on these changes.

Materials and methods: Male Fischer 344 rats were divided into a young group (age 6 months) and an old group (age 25 to 28 months), each with free access to normal food, and an old group (age 25 to 28 months) with food restricted to 3 days per week. Conscious cystometry, cDNA microarray analysis, immunohistochemistry and oxidative stress measurements of the bladder and dorsal root ganglia were performed.

Results: The old group with free access to normal food showed higher threshold pressure, more nonvoiding contractions and lower bladder compliance than the young group with free access to food. Old rats with free access showed greater post-void residual volume and lower voiding efficiency than old rats with caloric restriction and young rats. In the old group with free access 83 genes in the bladder and 48 in the L6 dorsal root ganglia were up-regulated compared with old rats with caloric restriction and young rats. These genes were mostly related to immune and inflammatory responses. Immunohistochemistry showed stronger expression of the immune response protease Gzm (granzyme) B and the collagenase Mmp13 (matrix metalloproteinase-13) in the bladder of old rats with free access vs old rats with caloric restriction and young rats. The level of malondialdehyde, an oxidative stress marker, was higher in the bladder of old rats with free access than in young rats but there was no difference between old rats with caloric restriction and young rats with free access to food.

Conclusions: In rats aging leads to storage and voiding dysfunctions associated with immune and inflammatory related responses in the bladder and dorsal root ganglia, and with increased oxidative stress in the bladder. Caloric restriction reduced these aging related changes.

Keywords: aging; caloric restriction; fibrosis; oxidative stress; urinary bladder.