Age-related remodeling of the JAK/STAT/SOCS signaling pathway and associated myocardial changes: From histological to molecular level

Background: The cellular and molecular mechanisms implicated in age-associated changes in myocardial structure are of paramount importance since they cause profound alterations in the functional response and represent targets for alleviating age-related pathologies. One of these mechanisms is the JAK/STAT/SOCS signaling pathway. Aim of the study: The present study is designed to elucidate age-dependent changes of the myocardium to provide morphological basis displaying the pathogenesis of myocardial hypertrophy, fibrosis and inflammation with aging. Material and methods: Thirty male Sprague Dawley rats aged; 6, 30 and 36 months were used in this study. The animals were divided into three age groups, young adult, senile and very senile rats, respectively. The heart weight/body weight ratio was determined. The heart was subjected to gross morphologic examination, microscopic examination using H&E and Masson's trichrome stains and immunohistochemical examination for detection of JAK, pSTAT3, alpha-SMA, beta-MHC and CD45. Western blotting was also carried out to detect SOCS genes. Real-time PCR was used to detect the inflammatory markers TNF alpha and IL1 beta and the hypertrophy marker alpha-SKA. Biochemical analysis of cardiac troponin I and creatine kinase-MB was done. Quantitative histomorphometric estimations included estimation of cardiac myocyte cross sectional area, estimation of the area percent of collagen fibers in Masson's trichrome stained sections and determination of optical density in immunostained sections. Electron microscopic examination was done to determine capillary density. Results: Jak and pSTAT3 were predominantly localized to the nuclei and exhibited progressive decline with aging, while SOCS3 activity displayed an age-related increase. The aged myocardium displayed profound age associated structural changes as well as myocardial hypertrophy, fibrosis and inflammation in senile and very senile rats. Conclusion: The age-related modifications in the JAK/STAT/SOCS signaling as well as the age-associated pathological changes in myocardial structure are of particular interest as they provide further insight in age-associated heart pathologies and represent potential targets for cardioprotective and therapeutic approaches. (C) 2017 Elsevier GmbH. All rights reserved.