Epigenetics is one of the most exciting fields of research. While it used to be thought that everything was in the genes, we now know that only around 20% is inherited directly and the remaining 80% of our lifespan is determined by epigenetic changes.
The average adult consists of the immense number of around 100,000,000,000,000 cells. With only a few exceptions, such as mature red blood cells, all of these cells have a nucleus in which the human genome is located. We already know this term from the first Hallmark of Aging – genomic instability. The genome is a term that simply describes the entirety of an individual's heritable information. This is information for the production of proteins that help determine and change the appearance of the body.
And what does epigenetics do now? Simply put, epigenetics determines which information is read and which is not. Here we will show you what effects epigenetics can have and what epigenetic changes have to do with age.
What does epigenetics do?
In every cell there is one and the same genetic information. How can it be that some cells become muscle cells and others become skin cells? The answer lies 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 DNA that essentially works 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 (OFF), it is considered silent and no protein is produced.
Perhaps for better illustration. Imagine your DNA is the text in a book. But 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, they are methylated sites on your DNA. They don't change your DNA per se, but rather determine which sections are read - and which are not. To make things even more complicated: The passages change in your life. Sometimes passages from one chapter are read and sometimes passages from the other chapter. And it also depends on which cell you are looking at.
Did you know? Epigenetics is used to determine biological age to be measured. Using the surface features of DNA and modern algorithms, it is now possible to calculate quite accurately how old a body cell is compared to its chronological age. This exact technique is also used in the epiAge test .
Almost more exciting is the fairly new method of measuring the proteins in the cells. With the help of so-called proteomics you go one step further and measure not the DNA, but the proteins produced. This allows a more modern and precise view of cell metabolism.
Do you know your biological age? The epiAge test has the answer.
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 can always be read or is used, but only parts of it for some proteins.
Accordingly, the number of proteins significantly exceeds the number of genes: science today estimates 20.000 to 25.000 human genes , the number of proteins in humans becomes 80.000 to 400.000 estimated. 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 will certainly help here. Using a neural network called AlphaFold, they have developed software that can predict the 3D structure of proteins.
The role of epigenetic fixation
The role of epigenetic fixation
Epigenetics, also known as epigenetic fixation or epigenetic imprinting, is the reason why different cell types develop from cells with the same requirements. They all have the same genome, but different epigenomes that tell them what proteins to produce 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? After we found out that we can find out the biological age with the help of epigenetic changes, the question still arises as to how we can influence this. In addition to exercise and fasting there are also some molecules that can help us reduce biological age . At the forefront is Calcium alphaketoglutarate (Ca-AKG). In human studies, it was able to reduce biological age by up to 7 years! In addition, it helps build muscle and bones and supports our mitochondria.
The combination with calcium ensures better AKG bioavailability in the organism.
Is epigenetics partly responsible for the obesity epidemic?
According to WHO figures, the rate of people being overweight has tripled since 1975. Accordingly, 1.9 billion people worldwide were said to be overweight in 2016.
Overweight, especially severe overweight with a high proportion of visceral fat, poses a risk for many age-related diseases, such as diabetes mellitus and cardiovascular diseases.
But where does this sharp increase in obesity come from? A large part is caused by incorrect eating habits and too little exercise, but epigenetics also have a hand in this.
Several animal experiments suggest that children of overweight parents receive epigenetic patterns that predispose them to gain more weight more quickly. The important point in the experiments was: It is often not the inherited genetics, but the inherited epigenetic pattern.
However, the good news here is that this pattern can be broken by e.g.b Through proper nutrition, the harmful epigenetic markers are replaced by new, more beneficial ones. How exactly something like this can look like in humans still needs to be further researched.
Epigenetic changes and aging
In contrast to the rigid DNA template of the genome, the epigenome changes throughout life. For example, changes occur during physiological development, but environmental factors such as stress, illness or nutrition also have an impact and not all changes are for the best.
Different epigenetic devices cause the changes. This complexity is also the reason why we are only paying attention to one, but very important, epigenetic mechanism: DNA methylation.
This foreign word refers to the transfer of special chemical molecules, the methyl groups, to the DNA. We leave out the remaining chemical subtleties for the sake of clarity. As a result of the addition of these chemical groups, the architecture of the DNA changes. While the stability suffers when building a house, with DNA it is only possible to read proteins in modified form. To go 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 also the transfer of methyl groups, usually require the presence of enzymes, as these create the optimal conditions. Accordingly, enzymes are also necessary 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 as time goes on. Epigenetic changes overall increase with age - a fact that the Horvath Clock takes advantage of.
Progeria and DNA methylation
A reminder: Progeria is a group of diseases with a strikingly (up to 10-fold) increased rate of aging. For example, it is possible for a ten-year-old girl with progeria to have a biological age of 70 years. You can find more details about progeria in the first Hallmark of Aging, the genomic instability.
In these people and also affected mice, researchers found similar methylation patterns to a large extent as in healthy people of old age. A connection between DNA methylation and age is already present. There is still no direct experimental evidence that the lifespan of the organism can be extended by changing DNA methylation patterns.
DNA methylation
Epigenetic changes – outlook
In contrast to DNA mutations, epigenetic changes are reversible. Based on this fact, opportunities arise for the development of new longevity treatments. The totality of current scientific evidence suggests that understanding and manipulating the epigenome holds promise for improving age-related pathologies. Inextricably linked to this is an extension of the healthy lifespan.
If you look at the enormous complexity of epigenetics on the one hand and the current state of research on the other, you realize, however, that there are still efforts, especially with regard to humans are in their infancy. The next years and decades will show to what extent tangible starting points for anti-aging and prevention can be derived from this. Ultimately, research is not a one-way street towards success - but it is definitely one towards understanding and enlightenment.
The next article in this series will focus on the fourth hallmark of aging: Loss of proteostasis.
