Calcium AKG’s Role In Extending Lifespan
If a genie offered you three wishes, many of us will think twice before asking to live to 100 Why? Because we imagine it'll just be a long period of suffering from age-related ailments. We all wish to live longer but in good health, which is why science is exploring calcium AKG as a possible solution to extend lifespans and delay age-related chronic health problems.
WHERE DOES ALPHA-KETOGLUTARATE COME FROM?
In order to discover the true benefits of calcium AKG or the calcium form of alpha-ketoglutarate, we must look in more detail at what alpha-ketoglutarate (AKG) is.
In 1937 Hans Adolf Krebs and William Arthur Johnson discovered alpha-ketoglutarate as part of the discovery of the citric acid cycle. AKG regulates the overall speed of the citric acid cycle of an organism. So AKG is a naturally occurring chemical that we create that forms part of the Kreb cycle. As a result of Hans Adolf Krebs' discovery, he received a Nobel Prize in 1953 and his name became known as the Krebs cycle.
WHAT IS AKG (ALPHA-KETOGLUTARATE)?
We just read that AKG is what is termed as a metabolite forming part of the Krebs cycle and that our own bodies create it. This special molecule is involved in a number of metabolic and cellular pathways. Although we are now aware of its role in the Kreb cycle, it is just one of the many crucial roles it plays in our bodies. It is actively involved in DNA methylation (the process our cells use to switch on the correct paths of our DNA). It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation. The gastrointestinal tract also uses AKG as a central metabolic fuel because glutamate and glutamine are both precursors of AKG. AKG can enhance bone tissue formation in the skeletal muscles by decreasing protein catabolism and increasing protein synthesis.
Unfortunately, as we age, we experience a dramatic decrease around 10 times between 40 and 80 years. It is concerning that such a crucial molecule in our bodies declines so radically as we age.
HOW DOES CALCIUM AKG EXTEND LIFESPAN?
Metabolism and ageing go hand in hand. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid cycle, and its levels change with fasting, exercise and ageing.
AKG has been used in various lifespan studies. This stems mainly from showing the inhibition of TOR (target of rapamycin). In a nutshell, TOR is like a central controller of cells, tissues and organism growth. AKG does not directly interact with TOR but does influence it, mainly via the inhibition of ATP synthase and this is what influences ageing in multiple species. Research has shown it slowed down ageing in yeast, expanded the lifespan C. elegans, slowed ageing in fruit flies and regulated lifespan in mammals, which we will explore in more detail below.
Dr Sinclair's performed a mammalian study he sought to determine if AKG had any effect on the health and lifespan of mammals. He looked at the role of AKG in DNA methylation. DNA methylation is the process which impacts how our body converts food into energy, our immune response, our brain chemistry, our response to stress, and how our bodies repair and respond to damage caused by free radicals. So when we age, our AKG levels drop and in turn, we're not activating those DNA bodily processes properly.
He used calcium AKG a form of Alpha-ketoglutarate (AKG) which has the calcium atom attached. AKG is used by the cell to make amino acids, energy & reverse the "DNA methylation" clock. The subjects were given a regular diet at the beginning of their lives and switched to a diet containing calcium AKG at 540 days.
The results were astonishing and as follows:
From the beginning of calcium AKG, the lifespan increased by 16.6 and 19.7%.
Subjects displayed improved hair quantity and quality, reduced frailty, and reduced spine curvature among rodents.
Significantly reduced conditions such as fur loss, dermatitis, gait disorder tumours, and eye discharge.
- Furthermore, there were no adverse side effects associated with supplementation of calcium AKG.
Dr Sinclair uses a diagram featured below to illustrate the effects of the endogenous metabolite on the lifespan of his subjects and goes more in-depth about the study.
“Alpha-ketoglutarate (AKG) is a chemical used by the cell to make amino acids, energy & reverse the "DNA methylation" clock. Feeding 18-month-old female mice AKG reduced hair greying, frailty & extended median lifespan 10-16%...”
— DR DAVID A. SINCLAIR
In animals, ageing-delaying interventions are well established; however, most have not been validated in humans. As humans live such long lives, analyzing their survival is impractical. Rather, ageing biomarkers, such as DNA methylation clocks (DNAm), can be used to determine biological age.
In Nov 2021, a paper concerning TruAge DNA methylation test was published in Aging Journal even though the data in this study are limited, it suggests that CaAKG does indeed influence ageing, at least as measured by methylation. After an average of 7 months of use, results showed a reversal of 8 biological years of age.
With further studies, scientists like Dr. Sinclair are very optimistic that the molecule, calcium AKG has made a mark and that it should translate to humans extending the human lifespan by some 8-10 years and “compressing morbidity,” which would save health care costs in the trillions.
WHAT ARE THE BENEFITS OF CALCIUM AKG?
Our DNA is constantly attacked by oxidative damage and by exposure to x-rays, UV light, toxins and chemicals. Our bodies respond by trying to reverse DNA changes through demethylation, a process we lose with age. By protecting DNA methyl patterns, calcium AKG allows genes to communicate better. A methylation profile that is healthy will also lead to healthy ageing.
Growing and repairing require protein, but eating produces ammonia as a byproduct. By detoxifying ammonia, calcium AKG increases the ability of your body's antioxidants to reduce the excess ammonia and assist your body's tissues in maintaining a chemistry balance.
In respiration, oxygen and glucose are converted into energy; AKG plays a key role in determining the overall rate of the Krebs cycle, which is the mechanism for this conversion. CaAKG provides us with molecular energy, which promotes an increase in energy production and reduces fatigue.
Calcium AKG blocks the excretion of inflammatory chemicals by senescent cells (SASP). The increase in the cellular response to inflammaging (age-related inflammation) reduces the low-grade inflammation that occurs during the ageing process.
- As part of the cellular metabolism, it provides glutamine and glutamate, which stimulate protein synthesis, inhibits protein degradation in muscle, and serve as fuel for gastrointestinal cells. Research has shown that Calcium AKG benefitted subjects' bones by increasing bone mass and improved hair, and skin.
IS CALCIUM AKG SAFE?
We know alpha-ketoglutarate is a naturally occurring chemical found in the body. Calcium AKG is AKG delivered as a calcium salt. People actually used AKG to make medicines for treating disorders like kidney disease, intestinal problems, and stomach troubles. AKG is sometimes administered intravenously (by IV) to prevent injury to the heart from blood flow problems during heart surgery or to prevent muscle breakdown after surgery or trauma.
Alpha-ketoglutarate is not available in the human diet. Exercise and fasting can promote an increase in the production of AKG, however direct supplementation is a more effective and feasible route to restore AKG levels. Dr Sinclair advises looking for a trusty supplier as it is better to consume a purified source of AKG. The FDA has granted GRAS status to AKG and its human safety record points to a potential safe human intervention with AKG that may improve the quality of life of elderly people.
“I believe that in the future, delaying and reversing aging will be the best way to treat the diseases that plague most of us.”
— DR DAVID A. SINCLAIR
Ageing starts at a cellular level and now we are all aware of AKG levels naturally declining between the ages of 40 and 80 years old. Science supports calcium AKG as a natural option to increase living organisms' lifespans. Should we not look towards supplementing a molecule that may extend our lifespan and improve our health?
We would all choose to grow younger than older and who knows calcium AKG, could make living to 100 in good health, something that we may no longer need to wish for.
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