Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 4 2026 10 31 Aging Induces Heart Injury via Mitochondrial Apoptotic Pathway and Dysregulation of Sirt1/Nrf2 Axis in Male Rats: Rescue Effect of Prazosin 536 543 10.34172/ps.43434 EN Aileen Saranjam https://orcid.org/0000-0002-7573-2770 Rahil Salimi Nasrin Mehran Fard Roya Naderi https://orcid.org/0000-0001-8529-7306 Journal Article 10.34172/ps.43434 2025 10 30 2026 06 14 Introduction: Myocardial aging is a significant contributor to heart dysfunction and subsequently heart failure. However, the underlying molecular mechanisms are not well understood. The goal of this study is to investigate how aging and Prazosin treatment affect apoptosis and Sirt1/Nrf2 signaling pathway in the hearts of aging rats. Methods: Eighteen male Wistar rats including 6 young rats (3-month-old; 200-250 g) in the Young control group and 12 aged rats (18-month-old; 400-450 g) were selected. They were divided into three groups (n=6): Young control, Aged, Aged + Prazosin (1 mg/kg; ip; intraperitoneally). Apoptosis was examined by TUNEL staining. The expression of Sirt1, Nrf2, Bax, and Bcl2 proteins were investigated by western blotting. Cytochrome c concentration was quantified by ELISA with a commercially available kit. The concentrations of CK-MB and LDH were determined using a spectrophotometric method with an autoanalyzer. Results: At the end of the experiment, the TUNEL staining indicated that aging increased the number of apoptotic cells in the hearts of male rats. Molecular analysis demonstrated that aging resulted in increased protein levels of cytochrome c, Bax/Bcl-2 ratio and also decreased protein levels of Sirt1 and Nrf2, with a concomitant up-regulation of LDH and CK-MB enzyme activities in the heart tissue compared to the young control group. Sirt1 and Nrf2 were negatively correlated with cytochrome c (r=-0.74, r=-0.90, P<0.001) and apoptosis (r=-0.81, r=-0.86, P<0.001). Conclusion: Our findings indicate that aging damages heart tissue via mitochondrial apoptosis and Sirt1/Nrf2 dysregulation, while prazosin reverses these changes, highlighting its potential as a therapy against age-related cardiac apoptosis. Furthermore, a negative correlation was identified between apoptosis and Sirt1/Nrf2.