AKG, DNA methylation and biological age
DNA methylation is a chemical modification of DNA that can affect gene expression. It occurs when a methyl group (-CH3) is added to the 5th carbon of a cytosine (C) nucleotide in DNA. This modification can silence genes by preventing them from being transcribed into RNA. They are a type of epigenetic mark, which means that they are not changes to the DNA sequence itself, but rather to the chemical structure of the DNA.
DNA methylation marks are usually found in clusters called CpG islands. CpG islands are regions of DNA that are rich in the sequence cytosine-phosphate-guanine (CpG). They are often found near the promoters of genes, which are the regions of DNA that control when and how genes are expressed. They can affect gene expression by either silencing genes or activating them.
DNA methylation marks can be inherited from parents to offspring, but they can also be changed by environmental factors such as diet, stress, and exposure to toxins. Changes in DNA methylation marks have been linked to a number of diseases, including cancer, heart disease, and Alzheimer's disease.
They are relatively stable, meaning that they can persist for long periods of time.
However, DNA methylation marks do change with age in a number of ways. Overall, there is a trend towards global hypomethylation, meaning that there is a decrease in the amount of methylation in the genome. This is thought to be due to a decrease in the activity of DNA methyltransferases, the enzymes that add methyl groups to DNA.
In addition to global hypomethylation, there are also specific regions of the genome that become hypermethylated with age. These regions often contain genes that are involved in aging, such as genes that control cell growth and DNA repair. Hypermethylation of these genes can lead to silencing of the genes, which can contribute to the aging process.
The changes in DNA methylation marks that occur with age are thought to be one of the factors that contribute to the decline in physical and cognitive function that is associated with aging. However, the exact mechanisms by which these changes lead to aging are still not fully understood.
Alpha-ketoglutarate (AKG) is a metabolic intermediate that is involved in a variety of cellular processes, including DNA methylation. AKG can act as a cofactor for enzymes that demethylate DNA, which can lead to changes in gene expression.
One study found that AKG supplementation in diabetic rats reversed aberrant methylation patterns and restored cardiac function. Another study found that AKG supplementation in mice with Alzheimer's disease reduced levels of amyloid plaques and improved cognitive function.
Another study showed that people taking an AKG supplement showed a reversal in biological age of 8 years after 7 months.
These studies suggest that AKG may have therapeutic potential for diseases that are associated with altered methylation patterns.
Some of the mechanisms by which AKG might affect DNA methylation include:
- AKG can act as a cofactor for DNA demethylases, the enzymes that remove methyl groups from DNA.
- AKG can also inhibit the activity of DNA methyltransferases, the enzymes that add methyl groups to DNA.
- AKG can promote the expression of genes that are involved in DNA demethylation.
- AKG can suppress the expression of genes that are involved in DNA methylation.
The exact mechanisms by which AKG affects DNA methylation are still not fully understood. However, the research that has been done so far suggests that AKG has the potential to be a powerful supplement to reverse age related changes to biological age as measured by DNA methylation.