α-Ketoglutarate Ameliorates Sarcopenia in D-Galactose-Induced Aging Mice by Modulating Protein Homeostasis and Optimizing Mitochondrial Function

This 2025 study in Nutrients tested whether AKG could protect against sarcopenia — the age-related loss of muscle mass, strength, and function — in mice aged prematurely with D-galactose, a well-established model for studying age-related muscle decline.

AKG-treated aging mice kept more muscle mass, ran further, gripped harder, and tolerated cold better than untreated aging mice — cold tolerance is a standard proxy for muscle-driven thermogenesis in this model. Looking inside the muscle, the researchers found AKG preserved the normal balance of protein building and breakdown (protein homeostasis), kept muscle fibres larger and better organised, and activated a specific antioxidant and energy pathway (SIRT1/PGC-1α/Nrf2) that improved mitochondrial function and cut oxidative damage.

This is preclinical mouse evidence, not a human trial — it does not establish that oral Ca-AKG preserves muscle in ageing people. But it is a mechanistically coherent, quantitatively detailed account of how AKG might support muscle in an aging biological system, and it directly strengthens the case that muscle and frailty are a genuine, biologically plausible domain for Ca-AKG research to focus on.