Health & Wellbeing

Promising naturally occurring anti-aging compound looks to human trials

Promising naturally occurring ...
A new mouse study has confirmed prior findings relating to anti-aging properties of AKG, laying the groundwork for a human trial
A new mouse study has confirmed prior findings relating to anti-aging properties of AKG, laying the groundwork for a human trial
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A new mouse study has confirmed prior findings relating to anti-aging properties of AKG, laying the groundwork for a human trial
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A new mouse study has confirmed prior findings relating to anti-aging properties of AKG, laying the groundwork for a human trial

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

7 comments
paul314
it's really hard to do longterm studies in these days where most companies barely see anything past the next quarter, and many researchers work year to year. Which is unfortunate for the human race.
Aross
As a senior this sounds really good. We don't necessarily want or need to live longer but improved health and mobility plus reduced pain from inflammation would sure be a boon.
Roger Royce
For all those thinking of going out to buy some AKG, most will likely find AAKG - as in Alpha-AKG. However, this study used Ca-AKG, a different formulation. Yes Ca-AKG is available if you look carefully on sites like Amazon, but it is NOT the commonly available supplement used in body building mixes and the like. Just saying it should be mentioned for full disclosure in articles like this one, so people don't run out and buy the wrong supplement form of AKG.

https://www.biorxiv.org/content/10.1101/779157v1.full.pdf

"Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms , can significantly extend lifespan and healthspan in
mice."
drBill
So we can get AKG from yeast and worms? Or do I have to buy some from GNC? Dose rate? There are some details...
BlueOak
"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."

No it does not. Classic association does not necessarily mean causation fallacy. Amateur "science".

So there might be a benefit in rodents - it is premature to get excited about humans.

But since AKG is already available as an exercise supplement, the AKG producers celebrate another sales channel. (Follow the money - who funded the study?)
akarp
Is this why keto-diets care correlated with lower inflammation?
undrgrndgirl
what what the supplemental dose in the mice? and what is an equivalent dose for humans?