This study investigates aging heterogeneity in diabetes-related tissues using the p21-3MR mouse model, focusing on p16 and p21 as markers of senescence. Type 2 diabetes, a common age-related disease, impacts multiple organs, and the study examines aging patterns in tissues such as the pancreas, kidney, heart, adipose tissue, femur, spleen, thymus, liver, and lungs. The results reveal significant aging heterogeneity and asynchrony across different organs during diabetes progression, with varying responses to anti-aging treatments. Specifically, the combination of dasatinib and quercetin demonstrated superior anti-aging effects in several tissues compared to p21 intervention alone, while p21 intervention showed distinct responses in adipose tissue and bone marrow. Immune organs displayed immunosenescence heterogeneity, and the liver and lungs showed greater sensitivity to vascular aging. This is the first study to use the p21-3MR model to explore aging heterogeneity and the differential effects of anti-aging treatments in diabetic tissues. The findings highlight the need for personalized anti-aging strategies, particularly in adipocytes and metabolic disorders. Future research should focus on understanding the mechanisms of p21 high cells in aging-related diseases, offering insights for more effective treatments.