New anti-aging ingredient pushes frontier of “healthspan”

A mammalian study published Sept. 1 in the esteemed journal Cell Metabolism demonstrated that an alpha-ketoglutarate ingredient with a proprietary extended-release delivery format—brand name LifeAKG—significantly extended lifespan and healthspan.

Even more immediate effects were seen among the rodents, from better hair quantity and quality to less frailty and reduced spine curvature.

The implications of this early study are provocative indeed—if translated to people, it could extend human lifespan by some 8-10 years and “compress morbidity,” which is the amount of time the elderly are sick or diseased. Health care cost savings could be in the trillions.

“Lifespan is how long you live. What really matters is how long you’re healthy, functional and disease-free,” said study researcher Brian Kennedy, director of the Center for Healthy Longevity at the National University of Singapore. “Aging is the biggest risk factor for almost every chronic disease you can think of.”

The study showed a lifespan extension of middle-aged female mice by 16.6% and a healthspan extension of both female and males. It showed an even more dramatic effect on frailty than lifespan.

“That’s what you really want,” Kennedy told the Insider. “What drives healthcare costs is the period when you’re sick and disabled late in life. Half of healthcare costs are in the last six months of life. If we can compress that, we can dramatically affect those costs.”

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Surveys show people don’t really want to live to be 100 years old, but that’s because they think it’s just going to be an extended period of time of broken-down lives with a poor quality of life—on oxygen, in pain, taking all kinds of pharmaceuticals.

“We’re trying to extend the time when you’re healthy so you can enjoy that time later in life,” said Kennedy. “At least for these mice that’s what we’ve been able to do.”

Anti-aging research legend

Kennedy is a renowned anti-aging researcher, having worked alongside David Sinclair at MIT where he discovered the sirtuin-1 gene that has been at the core of anti-aging research for the better part of the last two decades.

Sinclair went on to Harvard, where his revolutionary work on resveratrol showed effects on the sirtuin genes, which mimic calorie restriction and lead to expanded lifespan—in yeast, worms and mice. Sinclair sold his company, Sirtris, to pharmaceutical giant GlaxoSmithKline in 2008 for a whopping $720 million—but continued research on resveratrol failed to live up to expectations, and GSK shut down its acquired company five years later.

“We were not trying to slow aging,” said Kennedy, “just trying to understand pathways that regulate the aging process.”

Kennedy spent a handful of years studying anti-aging effects of the pharmaceutical drug rapamycin, but became impatient with the process of bringing a pharmaceutical to market especially for aging, which the FDA as yet does not identify as a disease state. So he shifted his work back to natural ingreidents for use in the supplements arena. 

Longevity meets personalized health care

Kennedy is also chief science officer of Ponce De Leon Health, a supplement company using the branded ingredient LifeAKG in its supplement brand, Rejuvant. 

Ponce De Leon was a famous Spanish explorer who searched for the Fountain of Youth (and discovered Florida).

“One of the exciting things we’re hearing with the sustained-release AKG LifeTabs,” said Kennedy, “anecdotally, people feel better in the present, have better exercise endurance and with that you get more energy, and reporting a variety of other effects as well. We need a controlled clinical study to really validate the effects.”

Kennedy is part of an upcoming human clinical trial, lasting between six and nine months, using LifeAKG to look at biomarkers that help define the epigenetic clock—think of it as describing one’s biological age instead of chronological age.

The Ponce De Leon Health supplements brand has a unique value proposition for consumers. For a monthly fee of $109, shoppers get a month’s worth of Rejuvant supplements as well as a DNA test kit. At seven months in the program, consumers get a second DNA test kit to take. Then they can compare results of biological markers to see if their personal biological age goes down, according to a raft of biomarker references.

After the results of the upcoming human clinical trial are completed, the company hopes to use some of the metrics used in the study parameters to build on its DNA testing program with consumers.

And that makes this DNA testing kit, along with an ingredient with demonstrated benefits in a published study, a new player in the game of using diagnostic testing results to power individualized supplements programs, making personlized nutrition ever more of a reality. Other such testing kits measure vitamin D levels, omega-3 levels, arterial flexibility as a way of revealing vitamin K2 levels, bacterial makeup in the gastrointestinal tract to inform probiotic consumption suggestions, and even DNA test kits that can inform the type of macronutrients a person should consume. 

Anti-aging ingredient No. 3

Kennedy said the difference with LifeAKG compared with the commodity alpha-ketoglutarate that was all the rage in gyms back in the 1990s is the extended-release technology, which allows the ingredient by stay intact past the stomach acids and release into the lower GI tract, where it can pass into the bloodstream. The company has also added vitamin A to the men’s formula and vitamin D to the women’s line, whereas standard alpha-ketoglutarate would often use amino acids such as arginine but to little apparent effect, according to Kennedy. 

“We saw additive effects on frailty when we combined those things,” said Kennedy.

After resveratrol, the second ingredient to grab the attention of anti-aging researchers was nicotinamide riboside. The problem with nicotinamide is it cannot be taken directly, so scientists discovered precursors, called simply NAD+. Both nitotinamide and AKG decline with age.

“The question is how effective are the precursors,” said Kennedy. “We are finding a bigger effect with AKG than NAD precursors.”

AKG has many observed effects. It increases red blood cell function, and because red blood cells carry oxygen it could be a reason for better exercise results. AKG also has other influences on biologic aging biomarkers, including the big one—inflammation. AKG also drives ATP production inside cells to make the mitochondria electron transport chain more active. Kennedy said he’s also seen improved adult stem cell function in animals taking AKG. Also seen is that AKG is a substrate for the enzyme that demethylates DNA, and that has a role to play in the epigenetic clock.

“That’s a lot of observations,” said Kennedy. “What it’s doing directly and then what’s the downstream effect of that. It’s like there’s a network and the pathways we’ve defined is just the edges of the network. The problem is when enough damage happens, that’s when the network starts to break down, and when it breaks down that’s when you start getting diseases. The key thing for a lot of these aging interventions is they preserve this network function, and given that everything is connected, maybe if they touch on two or three of these pathways maybe that improves everything. So if you look at all the pathways, you see benefits, but that doesn’t tell you the immediate thing that AKG is doing, and that’s what we’re trying to figure out right now.”