Other, pp.51-58, 2022
International consensus recognizes the impact of the aging process on the development of left ventricular hypertrophy in the heart. Both experimental and clinical data emphasize the intersection between aging and cardiovascular disease, which include age-associated co-morbidities such as metabolic syndrome, obesity, and diabetes that enhance the risk of developing cardiovascular disease. Indeed, cardiometabolic disturbances, including insulin resistance, contribute to aging-associated cardiac insufficiency and/or dysfunction. Cardiac aging is an intrinsic process accompanied by molecular and cellular changes (cardiac electrophysiological remodeling) mainly characterized by a long QT-interval, increased heart rate, and depressed cardiac output, as well as prolonged action potentials, altered sarcolemmal ionic currents and intracellular Ca2+-regulation at the cellular levels. Previous studies emphasize the benefits of insulin regulation as a critical component of pharmacotherapy after myocardial injury. Given the relationship between impaired insulin signaling and depression of various voltagedependent K+-channels, which in turn contribute to prolonged action potentials and long-QT in the heart, insulin treatment to restore proper cellular signaling may become an emerging new field for treatiing age-related heart dysfunction. This reviewarticle focuses on the molecular mechanisms linking insulin resistance, heart dysfunction, and advanced age in mammalians, including recent experimental results associated with the possible contribution of a right-shift of the voltage-dependency of tetrodotoxin-sensitive Na+-currents in ventricular cardiomyocytes from aged rat hearts, as well as the beneficial effects of insulin treatment in aged-rats on their cardiovascular function. Hopefully, this document will encourage scientists and clinicians in this field to design new and more effective mechanism-based insulin-like agents to improve myocardial performance in aged humans.