Abstract:
Atrazine (ATZ), a widely used and persistent environmental contaminant, poses significant risks to human health and food safety. Its association with cardiac fibrosis, oxidative stress, and aging phenotypes in cardiomyocytes is evident. Lycopene (LYC), a potent antioxidant from natural plant extracts, offers protection against cardiovascular diseases and aging. Despite this, the mechanisms of ATZ-induced cellular senescence and LYC's ameliorative effects on this senescence are not well understood. Our in vivo and in vitro investigations using Western blot, immunofluorescence, RT-qPCR, H&E staining, transmission electron microscopy, and SA-β-Gal staining reveal that ATZ/DACT suppresses Sirt3, causing mitochondrial dysfunction, and elevated ROS content and senescence markers in cardiomyocytes, effects that LYC can counteract. Modulation of Sirt3 expression by knockdown or overexpression showed that LYC's mitigation of DACT-induced senescence is Sirt3-dependent. This study confirmed that LYC can maintain mitochondrial function and reduce ROS content by regulating the expression of Sirt3, thereby alleviating ATZ/DACT-induced cardiomyocyte senescence. Our research uncovers the molecular basis of cardiac aging and provides new therapeutic avenues for environmentally induced cardiac aging-related diseases.
