Alpha-ketoglutarate (AKG) is a molecule that plays a crucial role in the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle or citric acid cycle. This cycle is a series of chemical reactions that occur within the cells of living organisms, converting nutrients into energy.

The TCA cycle is a central hub for cellular metabolism, and AKG is an important intermediate in this process. It’s generated during the breakdown of carbohydrates, fats, and proteins, and is used to produce energy in the form of adenosine triphosphate (ATP).

AKG also has other important functions in the cell, including:

1. Nitrogen metabolism: AKG is involved in the metabolism of nitrogen-containing compounds, such as amino acids, which are the building blocks of proteins.
2. Gene expression: AKG can act as a signaling molecule, influencing gene expression and the production of proteins within the cell.
3. Stress response: AKG can help regulate the cell’s response to stress, such as oxidative stress caused by the accumulation of reactive oxygen species (ROS).

As we age, the levels of AKG in our blood plasma tend to decrease. This decline may be associated with various age-related changes and diseases, such as:

1. Reduced energy production: Lower levels of AKG may impair the TCA cycle’s ability to generate energy, leading to cellular dysfunction.
2. Altered gene expression: Changes in AKG levels may affect gene expression, leading to the production of abnormal proteins or the loss of normal protein function.
3. Increased oxidative stress: Lower levels of AKG may compromise the cell’s ability to neutralize ROS, leading to increased oxidative stress and damage to cellular components.

Supplementing with AKG has been shown to have various health benefits in animal models, including:

1. Extended lifespan: AKG supplementation has been found to increase the lifespan of certain organisms, such as worms and fruit flies.
2. Improved metabolic health: AKG supplementation has been shown to improve glucose tolerance, insulin sensitivity, and lipid metabolism in animal models.
3. Reduced oxidative stress: AKG supplementation has been found to decrease oxidative stress and increase the activity of antioxidant enzymes in animal models.

While more research is needed to fully understand the effects of AKG supplementation in humans, it appears to have potential as a dietary supplement for maintaining metabolic health and overall well-being.