Promising naturally occurring anti-aging compound looks to human trials

An impressive new study from researchers at The Buck Institute for Research on Aging has found mice given supplements of an endogenous metabolite display significant healthspan improvements. The research follows on from other similar animal studies with the same compound, and a clinical trial in middle-aged humans is set to get underway.

Alpha-ketoglutarate (AKG) is produced endogenously in a human body as a product of natural metabolic processes. The molecule is not present in food, but its production can be enhanced by exercise or fasting.

AKG is commonly available as an exercise supplement. Some athletes and body-builders believe it can improve general athletic performance and help build muscle mass, however, there is only a small and inconclusive body of evidence supporting these claims.

Over the past few years some researchers have started investigating the effect of AKG supplementation on lifespan and healthspan. A 2008 review article on the subject noted AKG blood levels can drop by a factor of ten between the ages of 40 and 80. This suggests AKG supplementation in middle-age could confer helpful anti-aging effects into old age.

The new study, reporting the results of sustained AKG supplementation in mice, follows on from prior work detailing longevity effects from AKG in yeast and worms. From around 18 months of age, the mouse equivalent of middle-age, the animals were fed daily supplements of AKG for well over a year.

The AKG-supplemented mice lived, on average, 12 percent longer than the control mice. A relevant lifespan extension for sure, but looking into the effects of AKG on healthspan offered significantly more impressive results.

Many anti-aging researchers are primarily focusing on improving healthspan as opposed to lifespan. This means, instead of trying to keep us alive for decades longer, the goal is to extend the period of time we are vigorous and healthy. Gordon Lithgow, senior author on the new study, explains the focus on healthspan in this research.

“The nightmare scenario has always been life extension with no reduction in disability,” says Lithgow. “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.”

Healthspan was evaluated in the study using a number of measures including inflammatory markers, frailty and cognition. Overall, the AKG-supplemented animals showed more than 40 percent improvement across these healthspan measures compared to the control mice.

“Treatment with AKG promoted the production of Interleukin 10 (IL-10) which has anti-inflammatory properties and helps maintain normal tissue homeostasis,” explains Azar Asadi Shahmirzadi, another researcher working on the project. “Chronic inflammation is a huge driver of aging. We think suppression of inflammation could be the basis for the extension of lifespan and probably healthspan, and are looking forward to more follow up in this regard.”

It is still early days for the research, and although AKG supplements have been commercially available for several years, it isn’t clear whether there are negative effects from sustained long-term use. Researchers at the National University of Singapore are currently putting together a human clinical trial designed to test the effects of AKG in healthy middle-aged adults.

Of course, the trial will not be able to offer immediate data as to what effects AKG supplements generate after 10 or 20 years, but the research will look at a number of healthspan biomarkers to determine if there are signals to suggest sustained supplementation in middle-age could lead to improved health in one’s senior years.

“This trial will look at the epigenetic clock as well as standard markers of aging, including pulse wave velocity, and inflammation among others,” says senior co-author on the study, Brian Kennedy. “This opportunity will allow us to go beyond anecdotal evidence. Real clinical data will help inform physicians and consumers eager to improve health within the context of aging.”

The new study was published in the journal Cell Metabolism.

Source: The Buck Institute for Research on Aging

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