In short
Alpha-ketoglutarate (AKG) is a metabolic intermediate in the citric acid cycle (Krebs cycle) that also serves as a cofactor for enzymes involved in collagen synthesis and epigenetic regulation, and declines in circulating levels with age.
Beyond its central role in cellular energy metabolism, alpha-ketoglutarate is a required cofactor for a family of enzymes called dioxygenases, which includes enzymes involved in collagen hydroxylation (relevant to connective tissue and skin) and TET enzymes and Jumonji-domain histone demethylases, which are involved in modifying the epigenetic marks that epigenetic clocks measure — giving AKG a plausible mechanistic link to several aging-related processes beyond simple energy metabolism.
In C. elegans (roundworm) studies, AKG supplementation has extended lifespan, an effect partly attributed to mTOR inhibition and AMPK activation similar to caloric restriction's signaling effects, and a mouse study found a calcium-AKG formulation extended female mouse lifespan and improved several healthspan measures in aged mice.
The most cited human data point is a 2022 open-label study (Vaiserman et al./the company behind a branded calcium-AKG supplement) reporting a reduction in a proprietary composite epigenetic-age score after several months of supplementation in a small, uncontrolled group of adults — this is an early, methodologically limited human signal (no placebo control, small sample, and a biomarker rather than a clinical outcome), not a rigorous randomized trial demonstrating a health benefit. No trial has shown AKG extends human lifespan or produces a clinical outcome benefit, and the human evidence base remains considerably thinner than the animal-model data.