CDKN1A and Hyperinsulinemia: Mature human adipocytes undergo senescence under obesity and hyperinsulinemia stimulation, exhibiting premature aging transcriptomic and secretory characteristics, including upregulation of CDKN2A, CDKN1A, and CCND1 gene expression, and downregulation of HMGB1 and HMGB2 gene expression (101).