public RNA-sequencing data were leveraged to define how the transcriptome of healthy human arteries remodels with age, uncovering both known and novel age-dependent processes. We demonstrate for the first time that the SRF regulon is gradually depleted in the aging arterial wall, and that this, when mimicked by genetic SRF depletion in young mice, impairs contractility and elicits aortic remodeling and mucoid extracellular matrix accumulation which are hallmarks of aneurysmal disease. Moreover, aortic reduction of SRF mimics a molecular signature of Ang II treatment, an intervention that causes aortic aneurysm in and by itself.