Abstract
Brief Summary: This translational study evaluated cardiac health and lifespan in two cardiomyocyte-specific transgenic mice with either enhanced or reduced IGF-1 signaling and in human cardiac biopsies from failing and nonfailing hearts. Increased IGF1R expression was related to better cardiac performance in young mice but faster decline of cardiac function with aging. Conversely reduced IGF1R signaling was associated improved lifespan and superior cardiac profile during aging. Human failing hearts showed exaggerated IGF1R signaling. These data unveil a novel role of IGF1R signaling in cardiac health, which acts in a biphasic way according to age and suggest that the use of pharmacological inhibitors of IGF1 could be beneficial in elderly adults at risk of heart failure.
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