However, during the aging process, the dysfunction and decline of VSMCs have a detrimental impact on the structural integrity of the aorta, ultimately leading to the development of transthoracic aortic aneurysms.142 Classical molecular IGF-1 signaling causes cardiac hypertrophy and heart failure.142 IGF-1 increases cellular senescence in VSMCs by inducing DNA damage and increasing ROS production via the p53 pathway. Here, IGF1 is linked to heart failure.