What is epigenetics?

You may have heard about epigenetics in biology class, or you may have seen the Netflix series about the twin experiment. Either way, the term epigenetics has gained a lot of traction outside the scientific community in recent years. It seems that the old dogma that everything lies in the genes no longer applies.

Rather, research into epigenetics shows that we can influence some processes through our behavior, diet or exercise. In this article, we show you what epigenetics is, how epigenetics contributes to ageing research and what our grandparents have to do with it.

What is epigenetics?

Before we get into the subject, we need to clarify the definition: Epigenetics researches how changes that go beyond the genetic code have an effect - a concept expressed in the word part "epi", from the ancient Greek for "over" or "upon". The focus here is not on mutations as such, but rather on modifications that determine how active certain genes are in our cells.

A classic example of such modifications is DNA methylation. This involves attaching a methyl group (CH3) to specific sections of the DNA. This can have the effect of inhibiting certain cellular processes, for example by stopping the production of proteins. Epigenetics is responsible, for example, for the fact that a muscle cell differs from a kidney cell, even though both contain the exact same DNA sequence.

Epigenetics - a little simpler

If you haven't studied biochemistry, terms such as methylation, chromatin or non-coding RNA won't really mean anything to you. Don't worry, we'll explain epigenetics a little more clearly and use this analogy to try and explain the more complicated mechanisms behind it:

First of all, we need to take a closer look inside the cells. Each of our cells has the same strand of DNA, our genetic material. This contains all the information, e.g. how a heart muscle cell is structured, which proteins it contains or which enzymes a stomach cell must contain so that it can produce stomach acid and much more. If all this information were to be "read" at the same time, there would be a huge amount of chaos. For this reason, our DNA is full of chemical structures that can switch sections "on" or "off" like the switches on a volume control.

How "loud" are your genes?

Imagine that each gene on your DNA has such a volume control. With the help of this volume control, your epigenetics can set certain areas "loud" so that the gene is active or set other areas to "quiet", which makes this gene inactive. This fine-tuning is done by methylation. These small hydrocarbon groups determine how "loud" or "quiet" certain sections of the DNA in our genome are.

Another possibility is the so-called histone modifications. Histones are structural proteins around which the DNA is wound. Very similar to a curler. These proteins are also influenced by epigenetics. If they are modified, entire sections of DNA are more difficult to unwind and thus to read. Large parts therefore remain "silent" (inactive).

How are epigenetics influenced?

These epigenetic changes are influenced by various factors, such as environment, diet, stress and lifestyle. Some of these "volume settings" can even be passed on to future generations, which means that the experiences and conditions of your ancestors could influence which genes in your body are easier or harder to access. Epigenetics therefore ensures that, despite unchangeable genetic information, the accessibility and use of this information can be made dynamic and adaptable.

This explains how identical DNA in different cell types can lead to such diverse functions and characteristics. But it also explains why identical twins with exactly the same DNA have different characteristics. The exact settings of your "volume controls" are individual and can change constantly. This is known as an epigenetic pattern. You can make use of this if you want to measure the epigenetic or biological age.

DNA and epigenetics - what is inherited?

Each individual cell consists of 46 chromosomes. This is where the genetic information is stored in the form of DNA. The chromosomes are arranged in pairs, so that we have 23 pairs of chromosomes in each cell. We receive 50 percent of our chromosomes from our mother and the other 50 percent from our biological father.

Factor V Leiden: One of the most common genetic diseases

Imagine that one of your genes related to a certain topic (in this case factor V) is defective. This defective gene comes from your father, but fortunately your mother has passed on a whole copy to you. So you have two genes on the subject, but one of them is defective. In medicine, this is referred to as heterozygous expression.

This specific manifestation, a defective gene for factor V and a healthy one, is one of the most common "genetic diseases" in Europe. Around one in 20 people has a defective gene for factor V, which leads to a higher risk of thrombosis. If both genes are defective, one would speak of a homozygous form.

DNA and epigenetics - what is inherited?

The example of the defective factor V gene is typical of a hereditary disease. Epigenetics plays no role in this case, as the underlying information relating to the gene is defective. For a long time, it was believed that we only inherit the genes from our parents and only acquire epigenetics (i.e. the volume setting) later. According to current research, this is not correct. So do we also inherit some of the volume control presets from our parents?

Can trauma be inherited?

The eye color from the mother, the hair from the father and the psychological trauma from the grandparents? Although this is a rather bold statement, there is increasing evidence that we not only inherit DNA from our parents, but also epigenetic patterns and imprints - and this over several generations.

To stick with our analogy: It used to be assumed that volume control settings were not heritable. The differences in DNA methylation would only be acquired later in life. This assumption does not appear to be correct. In this study on fruit flies, scientists from the Max Planck Institute were able to show that epigenetic patterns can be passed on from generation to generation.

It is reasonable to assume that this is also the case in humans and perhaps new therapies can be developed from these findings in the future.

Can obesity be inherited?

Now that we have seen that certain epigenetic patterns can be inherited over several generations in fruit flies, the question arises as to what effects this can have. On the one hand, it is assumed that traumatic experiences can cause epigenetic changes that are also inherited and show up in later generations. You can find an interesting article in this ZDF Terra Xplore documentary, for example.

Another question is whether overweight parents pass on their epigenetic patterns to their children, making them more susceptible to obesity. Here, too, there is still a lack of direct evidence, but there are certainly indications that this is possible. In rats, for example, one study found that exposure to a pesticide (DDT = dichlorodiphenyltrichloroethane) led to a 50 percent incidence of obesity in subsequent generations.

This shows that environmental factors have the power to change epigenetic patterns and also promote obesity in subsequent generations. There is also evidence in humans that susceptibility to obesity is partly hereditary.

Epigenetics and biological age

Each of us has our own epigenetic patterns and yet we also have things in common. Steve Horvath was one of the first to recognize this. He investigated the question of how to measure biological age and used epigenetics to do so. The researcher developed the Horvath Clock, named after him, which can be used to measure the biological age of cells very accurately.

In the course of our lives, typical markings accumulate on our DNA. These marks are characteristic and the same for every person. The first epigenetic age test was developed on this basis.

The key to longevity?

The discovery of the Horvath Clock was so groundbreaking that he was awarded the Nobel Prize for it in 2017. For the first time, it was possible to measure the influence of various parameters on our cell health and age. Together with the Hallmarks of Aging, this laid the foundation for epigenetic ageing research. If we manage to reverse the epigenetic markers, we may be able to slow down or even stop ageing.

Researchers such as Harvard professor David Sinclair and American millionaire Bryan Johnson are already one step ahead and have tested (partly on themselves) a number of age-reducing molecules. Both have a significantly younger biological age, and new studies on the subject appear almost daily. In one study, for example, the biological age of humans was reduced by an impressive 8 years.

The secret? In the study, the test subjects took alpha-ketoglutarate, a molecule from the energy metabolism. If you want to find out more, you can read the background in our article on alpha-ketoglutarate. Further exciting research is being carried out in the field of NAD metabolism. The sirtuinsnicknamed "longevity genes", are also a key topic.

Proteomics - the next step?

DNA, epigenetics, longevity genes - ageing research is quite complex. Somewhere in this intricate network of metabolic pathways, the explanation for diseases or ageing itself will be hidden. To add another layer, we would like to introduce you to proteomics, because without this field of research, our picture will not be complete.

To give you an understanding of proteomics, we need to introduce a new analogy. The cell as a closet. While epigenetics uses its volume controls to determine which genes are active and which are inactive, proteomics looks at the result. Which proteins (items of clothing) are in your cell (closet)?

We can see what happens to the proteins after translation and how they interact with each other. You can find out more about this in our article on proteomics.