Longevity & AgingCholesterol Metabolism Decoded: From Cell Biology to Next-Gen Therapies
This comprehensive 2025 review from West China Hospital dissects how cholesterol is synthesized, absorbed, converted, and cleared, and how dysregulation drives atherosclerosis, fatty liver disease, neurodegeneration, and cancer. It traces the full biosynthetic cascade—from acetyl-CoA through the Bloch and Kandutsch-Russell pathways—alongside intestinal absorption via NPC1L1, bile acid production, steroid hormone synthesis, and lipoprotein-mediated clearance via LDLR and HDL. The authors catalog how disruptions in these pathways cause disease, then survey therapeutic advances: statins, PCSK9 inhibitors, siRNA therapies like inclisiran, CRISPR-based editing (VERVE-101), and novel targets including ANGPTL3 and Lp(a). Natural agents such as berberine and probiotics are also assessed. The review frames a shift toward personalized, multi-target lipid management in the genomic medicine era.
