Abstract Background The Western lifestyle, characterized by a diet rich in fat and fructose (HFHF), has been linked to metabolic disorders that accelerate aortic aging and damage, ultimately leading to the development of atherosclerotic cardiovascular diseases (ASCVD). Signaling pathways that promote cellular aging are associated with pathological changes. Our previous research has shown that activating TRPC7, a protein responsible for regulating cellular calcium homeostasis, leads to elevated levels of reactive oxygen species, DNA damage, and cellular aging, thereby initiating age-related pathogenesis. Metabolic disorders have also been linked to myocardial aging and damage. Therefore, investigating the impact of TRPC7 on the pathogenesis of metabolic disorder-associated aortic damage is of utmost importance. Purpose We aimed to examine the involvement of TRPC7 in the pathogenesis of metabolic disorders associated with aortic damage, which ultimately contributes to the development of ASCVD. Methods The study involved feeding mice an HFHF diet for 10 weeks, after which their body weight was recorded, and their aortas were harvested for analysis. Aortic thickness, lipid accumulation, and collagen content were measured. Immunohistochemistry staining was used to detect various markers, including DNA damage, senescence, senescence-associated secretory phenotype, and cell death. In addition, abnormal lipid production was screened using a lipidomic approach and bioinformatics tool. Results The study revealed that TRPC7 deficiency inhibited HFHF-induced increases in body weight and the ratio of adventitia to tunica media thicknesses, lipid accumulation, and collagen content in the aorta. Interestingly, lacking TRPC7 significantly reduced aortic pathogenesis induced by HFHF while upregulating DNA damage, senescence, SASP, and cell death in the mice fed with HFHF. In contrast, mice fed a regular diet, with or without TRPC7, showed no significant effects on body weight, aortic morphology, lipid droplets, DNA damage, senescence, and cell death in their aortas. Additionally, the study revealed that abnormal lipids, such as PC(18:0/20:4), PC(16:0/20:4), LacCer(d18:1/12:0), and PC(18:0/18:2), which can cause aortic aging and damage, were produced in mice fed with HFHF. However, in mice with deficient TRPC7, these abnormal lipids were not detected in their plasma. Conclusion Our study demonstrates that TRPC7 plays a crucial role in regulating metabolic disorder-associated aortic pathogenesis, leading to the progression of ASCVD. By inhibiting HFHF-induced aortic damage and aging, TRPC7 blockage shows promising effectiveness. Furthermore, the observed abnormal lipids production suggests TRPC7's involvement in lipid metabolism. These findings underscore the significance of investigating TRPC7 as a potential therapeutic target for preventing or treating metabolic disorder-associated aortic damage and related cardiovascular diseases.fig 1fig 2