3. Hallmark of Aging: Epigenetic changes

What does epigenetics do?

Every cell contains the same genetic information. So how can it be that some cells become muscle cells and others become skin cells? The answer is hidden in the cell nucleus.

We humans not only have a genome, but also an epigenome. The epigenome is a collection of chemical changes to the DNA that practically functions like a switch. Many genes have such a switch. If the switch is ON, the gene is "expressed", i.e. the blueprint is put into action and the desired protein is produced. If the gene is switched 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 because it is far too big, but only sections of it. So that you can remember which sections you want to read, you have stuck small post-it notes at the beginning and end of the text passage. These post-it notes are your epigenetic markers.

In chemical terms, these are methylated sites on your DNA. They do not change your DNA per se, but determine which sections are read - and which are not. To make things even more complicated: The sections of text 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 biological age . Using proteins in your cheek cells and modern algorithms, it is now possible to calculate fairly accurately how old a body cell is compared to its chronological age. This technology 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 of the information on a gene is always read or used, but only parts of it for some proteins.

Accordingly, the number of proteins significantly exceeds the number of genes: if science today assumes 20,000 to 25,000 human genes , the number of proteins in humans is estimated at 80,000 to 400,000 . More precise statements are currently difficult to make because research is still a long way from decoding all proteins.

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

The role of epigenetic fixation

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

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

Did you know Now that we have discovered that we can find out our biological age with the help of epigenetic changes, the question remains as to how we can influence it. Besides exercise and fasting there are also some molecules that can help us to reduce our biological age. At the forefront of this is calcium alphaketoglutarate (Ca-AKG). In human studies, it was able to reduce biological age by up to 7 years! It also helps to build muscle and bone and supports our mitochondria.

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

Is epigenetics partly responsible for the obesity epidemic?

According to WHO figures, the rate of obesity has tripled since 1975. Worldwide 1.9 billion people are said to have been overweight in 2016.

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

But where does this sharp rise in obesity come from? A large part is caused by poor eating habits and too little exercise, but epigenetics also has a hand in this.

Several animal experiments suggest that children of overweight parents receive epigenetic patterns that cause a predisposition to put on more 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 the harmful epigenetic markers with new, more beneficial ones through proper nutrition. However, further research is needed into exactly what this might look like in humans.

Epigenetic changes and aging

In contrast to the rigid DNA template of the genome, the epigenome changes throughout life. Changes occur during physiological development, for example, but environmental factors such as stress, illness or nutrition also have an effect and not all changes are for the best.

Different institutions of epigenetics cause the changes. This complexity is also the reason why we turn our attention to only one, but very important, epigenetic mechanism as an example: DNA methylation.

This foreign word refers to the transfer of special chemical molecules, the methyl groups, to the DNA. For reasons of clarity, we will omit the remaining chemical subtleties. As a result of the attachment of these chemical groups, the architecture of the DNAchanges. Whereas the stability of a house suffers, the reading of proteins in DNA is only possible in a modified form. To return 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 therefore also the transfer of methyl groups, generally require the presence of enzymes, as these create the optimum conditions. Accordingly, enzymes are also required 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 ageing?

Recent studies have shown that more and more methyl groups bind to the DNA over time. Epigenetic changes therefore increase in total with age - a fact that theHorvath clock makes use of.