Protective effects of cordycepin against d‐galactose‐induced aging in rats: A view from the heart

Aims Aging is a critical contributing factor for cardiovascular diseases. The d ‐galactose‐induced accelerated aging model is comparable to physiological aging from the cellular to the physiological level. The d ‐galactose treatment induces mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and upregulation of senescence‐related genes. Cordycepin, a functional element in Chinese traditional medicine, has multiple beneficial effects as an antioxidant and ROS scavenger, and has been reported to be effective in a number of ischemia models. This paper aims to investigate the cardioprotective effects of cordycepin in the d‐galactose accelerated aging model. Methods In the current study, we employed the d ‐galactose accelerated aging model to study the cardioprotective effect of cordycepin. Eight‐week‐old Sprague–Dawley rats, randomly divided into five groups, were given vehicle, d ‐galactose (150 mg/kg/day), and cordycepin at 5, 10, and 20 mg/kg per day. At the end of the 8‐week treatment, rat cardiac structure and function were assessed with echocardiographic imaging and hemodynamic parameter analysis. Results Cordycepin upregulated the expression of Klotho in serum and heart tissues. The expressions of senescence markers β‐galactosidase, p21, and oxidative stress marker malondialdehyde (MDA) were downregulated by cordycepin treatment. Reduction of levels and activity of the antioxidant factors superoxide dismutase (SOD) and catalase (CAT) induced by by d‐galactose treatment was ameliorated by cordycepin. Furthermore, cordycepin activated AMPK signaling in d ‐galactose‐treated rats. After 8 weeks of treatment, we found that cordycepin improved myocardia contractility and hypertension caused by d ‐galactose treatment. Mechanistically, reduced expression of the Klotho protein SOD1 caused by d ‐galactose was recovered in rats co‐treated with cordycepin. Conclusion Cordycepin could protect against cardiac dysfunction in a d ‐galactose‐induced aging rat model, suggesting the therapeutic cardioprotective potential of cordycepin in aging. Geriatr Gerontol Int 2022; 22: 433–440 .