Objective To investigate the mechanism underlying catch-up growth diet-induced metabolic syndrome and brain aging symptoms in C57 mice. Methods Forty C57 mice were randomly divided into four groups; a normal control group (n =10), a calorie-restricted group (n = 10), a high-energy-diet group (n = 10) and a catch-up growth group (calorie-restricted/ high-energy-diet group, n = 10). These animals were continuously fed for 12 weeks. The body weight and blood glucose of the animals were recorded, biochemical indicators of metabolic syndrome were detected at the end of the experiment, HOMA-IR was calculated, the expression levels of senescence-associated protein P53 and phosphorylated P53 (ser15) were determined by Western blot, and the lipofuscin deposited in the hippocampus was observed by electron microscopy. Results Compared with the normal control group, the calorie-restricted group had lower body weight, blood glucose, and biochemical indicators, its levels of P53 and phosphorylated P53 protein expression were downregulated, and lipofuscin deposition was reduced. Meanwhile, compared with the normal control group, the metabolic syndrome indicators of the high-energy group and the catch-up growth group were significantly higher, the levels of P53 and phosphorylated P53 protein expression were increased, and more lipofuscin deposition was observed. Furthermore, the catch-up growth group showed more pronounced insulin resistance and brain aging symptoms. Conclusions A catch-up growth diet can induce metabolic syndrome in mice with brain aging. This study provides new research ideas for the construction of animal models with metabolic syndrome and neurodegenerative dysfunction caused by different dietary patterns.