Gao P, et al. - Whether p53 is essential to the protective role of caloric restriction (CR) in abdominal aortic aneurysm (AAA) formation and underlying mechanisms was investigated in this study performed on p53^+/+ and p53^−/− mice. The mice were subjected to 12 weeks of CR and then evaluated for the incidence of angiotensin II(Ang II )–induced AAA formation. According to findings, Ang II–induced AAA formation was attenuated by both CR and p53 knockout. However, in p53^−/−mice, they found that CR resulted in a remarkable increase in the incidence of AAA formation and exacerbated aortic elastin degradation, accompanied by increased vascular senescence, reactive oxygen species generation, and reduced energy production. Mechanistically, the protective role of CR was almost completely blocked by ablation of p53; this happened via inhibition of cytochrome C oxidase assembly protein 2-dependent mitochondrial complex IV activity. According to the findings, an appropriate mitochondrial function was maintained by the presence of p53 in vascular smooth muscle cells was critical to the protective role of CR in Ang II-induced AAA formation.