The Role Of Nrf2 In D-Galactose-Induced Cardiac Aging In Mice: Involvement Of Oxidative Stress

Introduction: Cardiac aging is the major risk factor for advanced heart disease, which is the leading cause of death in developed countries, accounting for >30% of deaths worldwide. Objective: To discover the detailed mechanism of cardiac aging and develop an effective therapeutic candidate drug to treat or delay cardiac aging. Methods: We used D-galactose to induce cardiac aging in Nrf2(+/+) and Nrf2(-/-) mice, and then treated these mice with vehicle or the Nrf2 activator, CDDO-imidazolide (CDDO-Im). Results and Conclusions: D-galactose injection significantly induced cardiac aging, cell apoptosis, and oxidative stress in Nrf2(+/+) mice, all of which were further exacerbated in Nrf2(-/-) mice. CDDO-Im treatment can effectively weaken oxidative stress and enhance the activities of antioxidant enzymes, but CDDO-Im lost its antioxidative effect in the Nrf2(-/-) mice. Nrf2 activator CDDO-Im could therefore effectively protect against D-galactose-induced cardiac aging by inhibiting oxidative stress, suggesting that CDDO-Im might be a potential and promising therapeutic candidate drug to treat cardiac aging.