Longevity Key—Calcium Alpha-Ketoglutarate – ALIVE BY SCIENCE – Bioavailable NAD+ Boosters

Longevity Key—Calcium Alpha-Ketoglutarate


CaAKG Extends Healthspan in Mice by 10-16%

A multi-year, controlled study, conducted by the Buck Institute for Research on Aging in aged mice, found that calcium alpha-ketoglutarate (Ca-AKG), a stable form of alpha-ketoglutarate (AKG), promotes a longer, healthier life associated with a decrease in levels of inflammatory cytokines. 

Strikingly, the reduction in frailty was more dramatic than the increase in lifespan, leading the scientists to “propose that Ca-AKG compresses the period of morbidity. (Source)

“What is important about the study is the fact that adding calcium alpha-ketoglutarate to the diet not only delayed aging, it also compressed morbidity.  This study suggests that aging and associated comorbidities are not inevitable, and may likely be managed.”



“Researchers tracked two groups of mice beginning at 18 months of age (analogous to middle age) through the remainder of their natural lifespan.  The animals in both the control group and the CaAKG treated test group were observed for 31 frailty markers and tested for a multitude of biomarkers of aging and inflammation. 

Mice in the test group experienced a 12% increase in lifespan, and perhaps even more significantly, a 46% reduction in frailty, and 41% increase in healthspan.”

41% Increase in Healthspan

The molecule grabbed attention as a possible antiaging treatment in 2014 when researchers reported AKG could extend lifespan by more than 50% in tiny Caenorhabditis elegans worms. (Source)  That’s on par with a low-calorie diet, which has been shown to promote healthy aging, but it’s hard for most people to stick with.  Other groups later showed life span improvements from AKG in fruit flies. (Source)

Middle-aged mice that had the naturally-occurring metabolite alpha-ketoglutarate (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. (Source)

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. AKG is not found in the normal diet, making supplementation the only feasible way to restore its levels.

Reduction in Age-Related Frailty

The preeminent independent research showed sustained-release Calcium Alpha-Ketoglutarate may be an effective strategy in slowing down the aging process.  CaAKG increased the healthiest years of life.

“They looked much blacker, shinier, and younger”

In the landmark study, Gordon Lithgow and Brian Kennedy of the Buck Institute for Research on Aging and colleagues turned to mammals. They gave groups of 18-month-old mice (about age 55 in human years) the equivalent of 2% of their daily chow as AKG until they died, or for up to 21 months.

Some differences jumped out within a few months: “They looked much blacker, shinier, and younger” than control mice, says Azar Asadi Shahmirzadi, Ph.D.

Performed 40% Better

In addition, the AKG-fed mice scored an average of more than 40% better on tests of “frailty,” as measured by 31 physiological attributes including hair color, hearing, walking gait, and grip strength.

Hair discoloration and loss is one of the most common issues associated with human aging, and in mice, the results were visually clear.  Mice treated with CaAKG were visibly less discolored than untreated mice and retained considerably more of their hair.  This is likely to be due to enhanced stem cell function in melanocytes, which allow for the pigmentation of hair.

AKG may also enhance respiration and reduce inflammaging, the age-related inflammation that causes widespread and deleterious effects through our bodies. (Source)

Increases Life Expectancy

Lead researcher, Azar Asadi Shahmirzadi, observed that “what is important about the study is the fact that adding calcium alpha-ketoglutarate to the diet not only delayed aging, it also compressed morbidity.  This study suggests that aging and associated comorbidities are not inevitable, and may likely be managed.”

“The study allowed us to document healthspan changes that took place over time, including benefits in reduced frailty, reduced inflammation, and the increased physical activity in the calcium alpha-ketoglutarate group,” observed one of the trial’s senior researchers, Brian Kennedy, Ph.D. 

“Although the study was conducted on animals, humans share a number of major molecular aging pathways with mice and experience many of the same challenges to health associated with old age,” he continued.  “We are of the view that supplementation with calcium alpha-ketoglutarate may impact important elements of human aging and improve quality of life in the elderly population,” said Dr. Kennedy.

Decreased Levels of Systemic Inflammatory Cytokines

Treatment with AKG promoted the production of Interleukin 10 (IL-10) which has anti-inflammatory properties and helps maintain normal tissue homeostasis.  Mice fed AKG showed a decrease in levels of systemic inflammatory cytokines.

“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.” She also added, “We observed no significant adverse effects upon chronic administration of the metabolite, which is very important,” said Azar Asadi Shahmirzadi, Pharm.D, PhD.

Slows Down Aging and Fertility Decline in Mice

In a new study, researchers investigated the link between AKG and aging of the reproductive system in mammals, including mice, pigs, and humans.  Previous studies have also suggested that AKG declines in certain human tissues during aging. While ascertaining the mechanisms at play in this decline, they demonstrated that AKG has an influence on the age-related decline of fertility of mice. (Source)

Delayed Fertility Decline and Telomere Attrition

The mice treated with AKG retained ovarian function, with egg quality and quantity above that of untreated control mice of the same age.

The long-term supplementation of AKG also appeared to slow down the mice’s rate of telomere attrition, which is one reason that mice and humans are thought to age.  The researchers compared the telomere length in the ovaries of 14-month-old mice with those of 8-week-old mice.  As expected, the old mice in the control group had significantly shorter telomeres than the young mice.  However, the mice that had been given regular AKG had significantly longer telomeres than the control mice of the same age. (Source)

CaAKG – The Healthspan Extender You Need To Know About

Alpha-ketoglutarate (AKG) is a small compound, but plays a big role in our cells. Notably, AKG is a key component in the metabolic pathway, the Krebs Cycle.  However, levels of AKG have been shown to decline with age.  Delivered as a calcium salt (CaAKG), this recent publication shows that AKG can extend healthspan in both male and female mice, and extends lifespan in middle-aged female mice.


Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice

Cellular Compound May Increase Lifespan Without the Need for Strict Dieting

The Metabolite Alpha-Ketoglutarate Extends Lifespan by Inhibiting the ATP Synthase and TOR

Alpha-Ketoglutarate Delays Age-Related Fertility Decline in Mammals