Middle-aged mice that had the naturally-occurring metabolite alpha-ketaglutarate (AKG) added to their chow had a better “old age.” They were healthier as they aged and experienced a dramatically shorter time of disease and disability before they died, a first for research involving mammals. Results from the double-blinded study, published in Cell Metabolism, were based on clinically-relevant markers of healthspan.

Previous studies show that blood plasma levels of AKG can drop up to 10-fold as we age. Fasting and exercise, already shown to promote longevity, increase the production of AKG is not found in the normal diet, making supplementation the only feasible way to restore its levels.

“The standard for efficacy in research on aging is whether interventions actually improve healthspan. We’ve reached that mark here with a compound that is naturally produced by the body and is generally shown to be safe,” said Buck professor and senior author Gordon Lithgow, Ph.D… Noting that some of the mice did experience moderate lifespan extension (the average was around 12%), measures of healthspan increased more than 40 percent. Lithgow says the goal is always to compress the time of disease and frailty. “The nightmare scenario has always been life extension with no reduction in disability. In this study, the treated middle-aged mice got healthier over time. Even the mice that died early saw improvements in their health, which was really surprising and encouraging.”