Modulating Aging and Aging-Related Symptoms Using Endogenous Small Molecules

January 2019

Min Chai

α-ketobutyrate AMP-activated protein kinase autophagy α-ketoglutarate rapamycin metformin autophagy activators autophagy inhibitors α-KB AMPK α-KG

TLDR A molecule called α-ketobutyrate was found to extend lifespan and improve aging-related symptoms in worms and mice by activating certain cellular pathways and may help develop anti-aging treatments for humans.

The study identified α-ketobutyrate (α-KB) as a novel anti-aging metabolite that extended the lifespan of Caenorhabditis elegans and aged mice by acting as a competitive alternative substrate for pyruvate dehydrogenase, thereby rewiring pyruvate metabolism. The activation of the AMP-activated protein kinase (AMPK) pathway was necessary for α-KB to induce longevity and delay age-dependent paralysis in an Alzheimer’s disease C. elegans model. Additionally, α-KB improved fitness in aged mice, including maintaining healthy hair growth. The research highlighted the essential role of autophagy in the hair growth cycle and suggested that autophagy activators, such as α-KB, α-ketoglutarate, rapamycin, and metformin, could be potential therapies for hair loss. The study's findings on α-KB's anti-aging effects in worms and mice have implications for developing human anti-aging treatments.

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