The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Int J Mol Sci. 2024 May 11;25(10):5236. doi: 10.3390/ijms25105236.

Abstract

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.

Keywords: EMT; aged prostate; aging; caloric restriction; fibrosis; inflammaging; oxidative stress.

MeSH terms

  • Aging* / metabolism
  • Animals
  • Caloric Restriction* / methods
  • Fibrosis
  • Inflammasomes / metabolism
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Oxidative Stress
  • Prostate* / metabolism
  • Prostate* / pathology
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Rats
  • Rats, Sprague-Dawley*
  • Superoxide Dismutase-1 / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Transforming Growth Factor beta1
  • Inflammasomes
  • Superoxide Dismutase-1
  • Nlrp3 protein, rat
  • Sod1 protein, rat

Grants and funding

This research received no external funding.