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Also known as: AKG, Calcium Alpha-Ketoglutarate, CaAKG
A Krebs cycle intermediate that extended lifespan by 12% in mice (Buck Institute) and compressed morbidity — meaning animals lived healthier for longer, not just longer.
Alpha-Ketoglutarate (AKG) is a key intermediate in the Krebs (TCA) cycle and a critical cofactor for numerous enzymes. A landmark 2020 study from the Buck Institute showed that calcium AKG (CaAKG) extended median lifespan in mice by 12% and, remarkably, compressed morbidity — the mice spent less time sick before death.
Most longevity interventions extend both healthy years AND sick years proportionally. AKG is unusual because it specifically compressed the period of decline — animals were healthier for a greater percentage of their total lifespan. This is arguably more important than raw lifespan extension.
A commercial product (Rejuvant) containing CaAKG was tested in a small human trial using TruDiagnostic's biological age clock. Participants showed an average 8-year reduction in biological age after 7 months. While preliminary and industry-sponsored, the results are intriguing.
AKG is a cofactor for TET enzymes, which demethylate DNA. Age is associated with progressive DNA methylation changes. By supporting TET-mediated demethylation, AKG may partially reverse age-related epigenetic drift.
AKG serves as a cofactor for alpha-ketoglutarate-dependent dioxygenases, including TET enzymes (DNA demethylation), prolyl hydroxylases (collagen synthesis, HIF regulation), and JmjC histone demethylases (epigenetic regulation). It fuels the TCA cycle, supports amino acid metabolism, and inhibits ATP synthase under certain conditions (mimicking caloric restriction via AMPK activation).
Typical Dose
1000-2000mg
Frequency
Daily
Cycle Length
Ongoing
Half-Life
~1-2 hours
Buck Institute lifespan study (2020, Cell Metabolism). Human pilot trial for biological age. Active research. GRAS status.
Very safe — natural metabolite present in all cells. No significant adverse effects at supplemental doses. Calcium AKG form provides calcium co-supplementation. GI discomfort rare at recommended doses.
An mTOR inhibitor and FDA-approved immunosuppressant being investigated as the most promising pharmacological intervention for extending lifespan.
A direct NAD+ precursor that restores declining cellular energy metabolism and activates sirtuins for anti-aging effects.
The world's most prescribed diabetes drug, now being studied as a potential anti-aging intervention in the landmark TAME clinical trial.