Introduction

Epigenetics shows how the environment and our own habits influence our genetics and our disposition for diseases. The most important external factors that can influence our epigenetics are nutrition, sport and stress. In this article we will examine the connection between epigenetics, illness, sports and nutrition.

How does epigenetics affect you?

Epigenetics and diseases

In 1996, two identical twins, who wore the same mutation in a region of the X chromosome, developed different disease courses. Only one of the people who suffered from blindness, equilibrium disorders and loss of myelin in the brain: all signs of the neurological disease adreneoleukodystrophy (ALD). At that time, the researchers, who reported on the case, came to the conclusion that non-genetic factors had to be the cause of the different ALD phenotypes. Today we know that this was actually the case and that the causes were in the different epigenoms of the twins.

After that, similar cases were reported. Since epigenetics play an important role in regulating genes, it is not surprising that it plays a role in numerous diseases. Since epigenetics can suppress or intensify the expression of "good" and/or "bad" genes, epigenetic defects with diseases such as cancer, autoimmune diseases, metabolic syndromes, neuropsychiatric disorders or even asthma and (heart) vascular diseases can be associated or cause them. Some of these cases are shown in the next lines.

Genomic embossing

The genomic embossing is an epigenetic mechanism that determines whether the maternal or paternal copy of a gene is expressed in the descendants. In every generation, the parent -specific pregnant stamps must be deleted, reset and preserved. If one of the copies is "switched off" and the other copy is defective (e.g. by a mutation), this can have serious consequences for the individual. A number of diseases and disorders were associated with the genetic embossing, e.g. B. the Angelman syndrome, Prader-Willi syndrome and the Beckwith-Wiedemann syndrome.

Protein mutation

Another group of epigenetically conditioned diseases is caused by mutations in proteins that are essential for chromatin modification. These proteins are directly involved in the post-translational modification of histones and the methylation of the DNA or as a reader molecule of these modifications. For example, mutations in the Histon Acetyltransferasen CRBBP and EP300 are associated with the Rubinstein-Taybi syndrome. Mutations in the genes DNMT3B and ZBTB24, which are required for DNA methylation, lead to the syndrome of immune deficiency, centromic instability and facial anomalies. And mutations in the histone modification reader MECP2 cause Rett syndrome.

Epigenetic markers

A number of epigenetic biomarkers are associated with cancer and used for various clinical applications. For example, CPG methylation on a series of genome points was used precisely for the classification of subtypes of stomach cancer and subtypes of colorectal cancer. The DNA methylation on certain genes, such as BMP3, NDRG4, Sept9, was approved by the FDA as a marker for diagnosis of colon cancer. Histon markers were used preclinically for diagnosis of pancreatic cancer, e.g. B. H3K4 dimethylation, H3K9-acetylation and H3K27 trimethylation.

In neurology there is a number of epigenetic markers in the preclinical phase. For example, the methylation of the SNCA gene for the diagnosis of Parkinson's and the trimethylation of H3K9 for the diagnosis of Alzheimer's. Or the metylation of the genes app, Bace1, LRP1 and Sorl1 for the forecast of Alzheimer's disease.

In the event of autoimmune diseases, epigenetic markers could be used for disease forecast in the future. For example, the methylation of interferon and interleukin genes is used for the forecast of lupus.

Epigenetics are also associated with metabolic disorders such as type 2 diabetes and obesity. Diet can strongly influence our epigenetics. More on this in the blog post "The effect of fasting on epigenetics".

As already mentioned, the identification of certain epigenetic markers that are connected to certain diseases can provide funds for diagnosis, monitoring and development of measures that can reduce the risk or burden on the disease. Moleqlar Analytics supports the pharmaceutical industry in the discovery of new epigenetic biomarkers and in evaluating the effects of medication and treatments on the epigenetics of people.

How do you influence epigenetics?

Epigenetics and sport

Have you ever wondered why some of our bodies react differently than others, even if you do exactly the same exercise? It has been shown that the genetic equipment plays a major role when untrained people carry out certain physical activities, with some better and other worse off [1].

Studies on transcriptomics (examination of RNA transcripts) and proteomics (examination of proteins) have shown that our gene expression patterns adapt to the type of sporting activity [1]. For example, people who train their perseverance apparently have other gene expression patterns in the skeletal muscles as people who train their strength [1]. But it's not just about our genetic code.

In order to illuminate the molecular and systemic effects of physical activity in more detail, an important aspect must be taken into account: epigenetics. It has been proven that physical activity has an impact on histone modifications in muscle and brain tissue as well as on the DNA methylation status in muscle tissue [2, 3]. For example, it was suspected that physical activity leads to a DNA methylation of genes that are involved in chronic inflammation and tumor suppression [4].

In order to come back to the example of the skeletal muscles: histonedeacetylases (HDAC), enzymes that remove an acetyl group from a histone, are primarily responsible for the epigenetic changes of the histones [2]. HDACS affect the suppression of the transcription factor Myocyte Enhancer Factor 2 (MEF-2), which in return suppresses the formation of slowly twitching oxidative myofibers [2]. However, the overexpression of MEF-2 by selective breakdown of HDACs in the skeletal muscle of mice promoted the formation of slow myofibers and improved the running endurance, so that these transgenic mice could run almost twice as far as wild type mice [2].

Other studies have shown that sporting activity increases the expression of genes and proteins of the glucose van (glut4) in human skeletal muscles, which generally increases the insulin effect throughout the body [5]. After exercising, the nuclear HDACs were reduced by more than half, and the Association of the HDACs with MEF-2 was reduced by more than a quarter [5].

There are several epigenetic changes associated with physical activity. They therefore represent potential therapeutic goals for different diseases (e.g. the regulation of glut4 expression in diseases such as type 2 diabetes). Together with partners, Moleqlar Analytics wants to deepen our understanding of the effects of physical activity on us and our epigenetic properties.

Epigenetics and nutrition

Consumption of food can cause changes in our epigenetics and thereby affect individual health by influencing the catalytic activities of the enzymes Writing, deleting and reading epigenetic changes are responsible.

It is known that a number of metabolic products from food (with more or less scientific evidence) influence DNA methylation and histone modifications;

For example, it has been shown that consumption of Concord grape juice reduces the depression values ​​for mice, which is due to the presence of dihydrochanic acid (DHCA) in this drink. DHCA is an inhibition of DNMT1, a writer of the DNA methylation of the GEN IL-6, which, if it is methylated, increases the depression values.

Another ingredient in the Concord drink is Malvidin-3'-O-Glucoside (Mal-Gluc) that lowers the stress level. Mal-Gluc is an inhibitor from HDAC2, a so-called eraser for Histon-H3 acetylation on the RAC1 gene. If the H3 acetylation on this gene is high, the stress level sinks in mice.

Another example of how nutrition affects our epigenetics was found in a common food preservative: sodium benzoat. Sodium benzoat is converted metabolic into benzoyl coa in our body. It has been shown that this derivative is used by writer molecules to increase histone benzoylation. The effects of this epigenetic change are still unknown.

As can be seen from the table above, some other metabolites can also cause changes in the epigenoma. At Moleqlar Analytics, we work with business partners from the nutrotional industry in order to evaluate the effects of nutrition and nutritional supplements on the epigenetics of the individual.