Longevity & AgingAlpha-Ketoglutarate Reverses Cartilage Damage in Osteoarthritis via Epigenetic Reprogramming
Researchers at Tongji University discovered that osteoarthritis (OA) impairs glutamine metabolism in chondrocytes through epigenetic silencing of key transporter and enzyme genes. Alpha-ketoglutarate (αKG), a TCA cycle intermediate, countered this by activating the demethylase Kdm6b, which removed repressive H3K27me3 marks from glutaminolysis genes and the ubiquitin-ligase gene Ube2o. Elevated Ube2o then ubiquitinated TRAF6, suppressing NF-κB signaling and restoring metabolic balance. In both surgically induced and obesity-related mouse OA models, αKG supplementation significantly reduced cartilage degradation, establishing a TCA- and HIF-1α-independent therapeutic mechanism.
