Note: Since I’m leaving on vacation tomorrow (Yellowstone baby!), we’ve got a special guest post for you this week from Dr. Kris Verburgh and the fine folks at Novos Labs; a longevity supplement startup targeting multiple aging hallmarks with different life-extending compounds. They’ve been featured on Longevity.Technology and also have a fantastic blog we’ll link to below that’s worth checking out. Since our next content block will be all about different anti-aging supplements and the science behind them, we thought this overview of Alpha-Ketoglutaric Acid (AKG) for longevity would serve as a nice teaser for when we finish up diet and nutrition in October and switch over. So without further ado, take it away, Kris!

In the last few years, we have seen the rise of more science-based supplements to slow down aging. 

Various companies have emerged that want to use a more scientific approach to develop anti-aging supplements. This is very good, because prior to this new wave, most “anti-aging” supplements had very little or no science behind them. 

Even worse, many supplements that claim to be “anti-aging” may even accelerate aging, like those that contain specific antioxidants (studies have shown that most antioxidants don’t extend lifespan, and that some could actually accelerate aging).

Luckily, there are various ingredients that have lots of science behind them when it comes to slowing down aging, and to increase health throughout the aging process. 

One such ingredient is alpha-ketoglutaric acid, or alpha-ketoglutarate (AKG). For many decades, AKG has been used by athletes and fitness fans to increase stamina and energy.

However, AKG can do much more.

Health benefits of AKG

Earlier studies showed that AKG can reduce the side effects and provide protection of organs during very demanding operations, such as during heart surgery.

Intrigued by these effects, scientists decide to look further into AKG. Studies in different organisms demonstrated that AKG can extend lifespan, including in fruit flies, roundworms, and mice.

The healthspan extension by alpha-ketoglutarate is often more striking than the lifespan extension. That means that AKG could help to keep old organisms healthier for longer, “compressing morbidity” while also extending lifespan.

Alpha-ketoglutarate can impact lifespan and health via various mechanisms. For example, AKG plays a role in maintaining a healthy epigenome. 

The epigenome is the intricate molecular machinery that surrounds the DNA and determines which genes are switched on or off. The older we get, the more the epigenome becomes dysregulated. For example, health-promoting and cellular housekeeping genes are switched off more when we get older, while cancer-promoting or pro-inflammatory genes are more switched on, which contributes to the aging process. Epigenetic dysregulation is an important cause of aging. 

Alpha-ketoglutarate helps specific epigenetic proteins, like TET enzymes, to maintain the epigenome. Interestingly, AKG works together with vitamin C for this. Vitamin C, often touted for health simply as an “antioxidant,” has various healthy epigenetic effects too.

Alpha-ketoglutarate is also fuel for our mitochondria. The mitochondria are the power plants of our cells. The older we get, the less well our mitochondria function. AKG can help the mitochondria to function better and to protect them. That is one reason why athletes take AKG for more stamina (energy), and why AKG could be protective during heart operations, in which the mitochondria are starved from oxygen and very prone to damage. 

Alpha-ketoglutarate can also reduce inflammation. This is interesting, because the older we get, the more inflamed our bodies become. This is called “inflammaging,” and this low-grade systemic inflammation fuels the aging process and increases the risk of many aging-related diseases, including heart disease and Alzheimer’s.

Alpha-ketoglutarate has many other roles in the body. For example, it is also involved in collagen production, and could theoretically help for a better skin. Interestingly, in lifespan studies in mice, researchers found that AKG also reduces hair greying in old mice. It is speculated that this is due to the beneficial effect of AKG on the stem cells in the skin that maintain the melanocytes, which are cells that give hair its color. Other studies show that AKG can improve stem cell health.

Beyond AKG

This and other findings led us at NOVOS to use alpha-ketoglutarate in our formulation. However, there are different forms of alpha-ketoglutarate. Most supplements provide plain alpha-ketoglutarate, or arginine alpha-ketoglutarate, but the most interesting lifespan studies have been done with calcium alpha-ketoglutarate (caAKG). Calcium alpha-ketoglutaric acid enables the alpha-ketoglutarate to be broken down slower, and also has the most science behind it to extend lifespan.

Alpha-ketoglutarate is a good example of a much more science-based substance to impact aging. But only using AKG is not enough to significantly slow down the aging process. There are many reasons why we age, and AKG can also address only a few of them, in a very specific way. 

Therefore, we believe that the best supplements to address aging need to contain multiple ingredients. Examples of other promising, science-based anti-aging compounds are microdosed lithium, fisetin, glucosamine, pterostilbene, and so on.

Closing note: Thanks for sticking around for this AKG overview from Kris and Novos Labs! We’re excited to get into the science behind some other promising longevity compounds, and hope you’ll check out the Novos blog where they break down a whole host of supplements as well.

Kris Verburgh

Kris Verburgh is co-founder of NOVOS, a company that develops nutraceuticals and solutions to slow down aging. He is a medical doctor and an expert in aging and longevity, and in new developments in medicine and biotechnology. He is a researcher at the Free University of Brussels, and faculty member at Singularity University Benelux where he teaches about the future of medicine and longevity. He is a partner at a $100 million fund that invests in new technologies to address aging. He wrote his first science book when he was 16 years old, and by age 28 he had written four science books. He has given talks on health, longevity, new developments in medicine and biotechnology for various organizations and institutions, including the European Parliament, Cambridge University, and international companies and banks.

J.P.

I’m the co-founder of Longevity Advice and have been passionate about radical life extension ever since I was a teenager. Formerly I was a content marketing director in the B2B software space. I’m also a sci-fi novelist, wargame rules writer, and enthusiast for cooking things in bacon fat. My sister once called me “King of the Nerds” and it’s a title I’ve been trying to live up to ever since.