3. Hallmark of Aging: Epigenetic changes

What does epigenetics do?

In every cell, there is the same genetic information. How can it be that some cells become muscle cells while others become skin cells? The answer is hidden in the cell nucleus.

We humans possess not only a genome but also an epigenome. The epigenome is a collection of chemical changes to the DNA that functions practically like a switch. Many genes have such a switch. When the switch is ON, the gene is "expressed," meaning: the blueprint is put into action and the desired protein is produced. When the gene is turned off (OFF), it is considered silent and no protein is produced.

Perhaps for better illustration. Imagine your DNA is the text in a book. However, you never read the entire book, as it is far too large, but only sections of it. To remember which sections you want to read, you have stuck small Post-It notes at the beginning and the end of the text passage. These Post-it notes are your epigenetic markers.

Chemically expressed, these are methylated sites on your DNA. They do not change your DNA itself, but determine which sections are read – and which are not. To make things even more complicated: The text sections change throughout your life. Sometimes passages from one chapter are read, and sometimes passages from another chapter. And it also depends on which cell you are looking at.

Did you know? Epigenetics is used, to measure the biological age of cells. Based on proteins in your cheek cells and modern algorithms, it can now be calculated quite accurately how old a body cell is compared to chronological age. This very technique is also used in our Epiproteomics Test .

The diversity of genes

Each gene contains the blueprint for one or more proteins. This is made possible by a process called "alternative splicing". This means that not all the information in a gene is read or used, but only parts of it for some proteins.

Accordingly, the number of proteins significantly exceeds the number of genes: While science currently estimates 20,000 to 25,000 human genes , the number of proteins in humans is estimated to be between 80,000 and 400,000 . More precise statements are currently difficult to make because research is still far from deciphering all proteins.

Helping will certainly be a groundbreaking development of the company DeepMind, which has developed software with the help of a neural network called AlphaFold that can predict the 3D structure of proteins.

The role of epigenetic fixation

Epigenetics, also referred to as  epigenetic fixation  or  epigenetic imprinting , is the reason,  why different cell types develop from cells with the same conditions. They all have the same genome, but different epigenomes that tell them which proteins need to be produced and  what type of cells they ultimately need to be.

In addition, epigenetics, at least according to current research, is partially heritable.Research on epigenetics is still a relatively young field, but there are already some exciting results.

Did you know? After we discovered that we can determine biological age through epigenetic changes, the question remains how we can influence it. In addition to  exercise and fasting , there are also some molecules that can help us reduce biological age.  At the forefront is  Calcium Alpha-Ketoglutarate (Ca-AKG). In human studies, it was able to reduce biological age  by up to 7 years! Additionally, it also helps with muscle and bone development and supports our  mitochondria.

The combination with calcium ensures better bioavailability of AKG in the body.

Is epigenetics partially responsible for the obesity epidemic?

According to WHO figures, the rate of overweight individuals has tripled since 1975. Worldwide, it is estimated that 1.9 billion people were overweight in 2016 .

Overweight, especially severe obesity with a high visceral fat percentage, poses a risk for many age-related diseases, such as diabetes mellitus and cardiovascular diseases.

But where does this significant increase in overweight come from? A large part is due to poor eating habits and insufficient exercise, but epigenetics also plays a role here.

Multiple animal experiments suggest that children of overweight parents inherit epigenetic patterns that predispose them to gain weight more quickly. The important point in the experiments was: It is often not the inherited genetics, but the inherited epigenetic pattern.

The good news here, however, is that this pattern can be broken by z.B. replacing harmful epigenetic markers with new, more beneficial ones through proper nutrition. However, how exactly this might look in humans still needs to be further researched.

Epigenetic changes and aging

The epigenome changes throughout life, in contrast to the rigid DNA matrix of the genome.Changes occur, for example, during physiological development, but environmental factors such as stress, illness, or nutrition also have an impact, and not all changes are for the better. Different mechanisms of epigenetics cause the changes. This complexity is also the reason why we will focus our attention on just one, but very important epigenetic mechanism: DNA methylation. This foreign term refers to the transfer of special chemical molecules, the methyl groups, onto the DNA. We will omit the remaining chemical intricacies for the sake of clarity. As a result of the attachment of these chemical groups, the architecture of the DNA changes.Whereas in house construction stability suffers, in DNA the reading of proteins is only altered possible. To refer back to our analogy from the beginning. The DNA methylations are the colored Post-it notes that tell you whether you want to read the text behind them or not.

Chemical reactions in the body, and thus the transfer of methyl groups, usually require the presence of enzymes, as they create the optimal conditions. Accordingly, enzymes are also needed here, the so-called DNA methyltransferases (enzymes that transfer the methyl groups to the DNA). What does this rather complicated input have to do with aging?

Recent studies have shown that more and more methyl groups bind to the DNA over time.Epigenetic changes increase with age overall – a circumstance that the  Horvath Clock  takes advantage of.