Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal disorder that causes premature aging, affecting approximately one in 4–8 million births. Most cases result from a mutation in the lamin A/C (LMNA) gene, leading to the production of progerin, an aberrant lamin A variant that disrupts nuclear architecture and alters gene expression, including microRNA (miRNA) deregulation. This study aimed to investigate the molecular mechanisms underlying HGPS and aging using global miRNA sequencing to identify key deregulated miRNAs. Both miR-145 and miR-27b were significantly altered in HGPS. Functional experiments further revealed their crucial role in adipogenesis. Downregulation of these miRNAs in HGPS cells enhanced adipocyte differentiation, whereas their upregulation in control cells suppressed this process. These findings indicate that elevated levels of miR-145-5p and miR-27b-3p impair adipogenesis, providing mechanistic insights into HGPS pathophysiology and highlight new potential therapeutic avenues for both HGPS and metabolic disorders.