While aging is a critical risk factor for
heart failure, it remains uncertain whether the aging heart responds differentially to a hypertensive stimuli. Here we investigated phenotypic and transcriptomic differences between the young and aging heart using a
mineralocorticoid-excess model of
hypertension. Ten-week ("young") and 36-week ("aging") mice underwent a unilateral uninephrectomy with
deoxycorticosterone acetate (
DOCA) pellet implantation (n = 6-8/group) and were followed for 6 weeks. Cardiac structure and function, blood pressure (BP) and the cardiac transcriptome were subsequently examined. Young and aging
DOCA mice had high BP, increased cardiac mass,
cardiac hypertrophy, and
fibrosis. Left ventricular end-diastolic pressure increased in aging
DOCA-treated mice in contrast to young
DOCA mice. Interstitial and perivascular
fibrosis occurred in response to
DOCA, but perivascular
fibrosis was greater in aging mice. Transcriptomic analysis showed that young mice had features of higher oxidative stress, likely due to activation of the respiratory electron transport chain. In contrast, aging mice showed up-regulation of
collagen formation in association with activation of innate immunity together with markers of
inflammation including
cytokine and platelet signaling. In comparison to younger mice, aging mice demonstrated different phenotypic and molecular responses to hypertensive stress. These findings have potential implications for the pathogenesis of age-related forms of
cardiovascular disease, particularly
heart failure.