Alpha-Ketoglutarate (AKG)

Alpha-Ketoglutarate (AKG) delivers the strongest epigenetic rejuvenation signal in biohacking, anchored by the Rejuvant trial (PMC8660611) which found a mean biological age reduction of approximately 8 years over seven months using the Horvath DNA methylation clock. AKG is a central TCA cycle metabolite that regulates DNA methylation and histone modification via TET enzymes and Jumonji-domain demethylases, directly countering epigenetic drift. It also inhibits ATP synthase to activate AMPK (mimicking caloric restriction), inhibits mTOR signaling, and serves as a precursor for glutathione—the primary intracellular antioxidant. This positions AKG at the convergence of five aging pathways: epigenetic regulation, nutrient sensing, mitochondrial function, oxidative stress, and proteostasis. A follow-up RCT (NCT07114536) is underway with larger sample size. AKG is available OTC as calcium AKG dosed at 1–2 grams/day, costing around $50/month for quality formulations, with minimal side effects.