Dehydroepiandrosterone opposes cardiac aging via NFκB/IL-10/Sirt1/Nrf2 mediated pathway in aged rats

Cardiovascular aging is characterized by structural and functional deterioration of the heart, mediated by chronic inflammation, oxidative stress, and impaired cellular defense pathways. Dehydroepiandrosterone (DHEA), a steroid hormone with known anti-inflammatory and antioxidant properties, declines with age and may have therapeutic potential in ameliorating cardiac aging. The aim of the present study was to test the hypothesis that replenishing DHEA can counter the age dependent decline in cardiac functions. The possible underlying mechanisms were also tested.

Thirty male Wistar rats were divided into three groups: control, aged, and aged treated with DHEA (30 mg/kg/day via intraperitoneal injection for 4 weeks). Cardiovascular parameters (SBP, DBP, HR), biomarkers of myocardial insult (troponin I, CK-MB, myoglobin, LDH, and GP-BB), cardiac performance (lactic acid and treadmill endurance test), markers for inflammation (NFκB and IL-10) and oxidative stress (MDA and TAC), and the gene expression of NFκB, IL-10, Sirt1 and Nrf2 were assessed.

Aging was associated with significant increases in SBP, DBP, HR, serum levels of myocardial injury markers, lactic acid, NFκB and MDA, and cardiac muscle NFκB gene expression. Aging was also associated with reduced cardiovascular endurance, serum levels of IL-10 and TAC, as well as cardiac muscle IL-10 Sirt1 and Nrf2 gene expression. Administration of DHEA significantly improved all affected parameters compared to untreated aged rats. Nevertheless, control-comparable values were not achieved. Notably, DHEA downregulated cardiac muscle NFκB while it upregulated IL-10, Sirt1, and Nrf2 gene expression, suggesting a possible common anti-inflammatory/antioxidant pathway.

DHEA supplementation in aged rats mitigated cardiovascular aging by improving hemodynamic parameters, reducing myocardial injury, demoting inflammation, enhancing antioxidant capacity, and activating key protective genes. Our findings support a potential therapeutic value of DHEA in modulating age-dependent decline in cardiac functions through a possible NFκB/IL-10/Sirt1/Nrf2 pathway.