In recent years, research in genetics and epigenetics has garnered increasing attention, opening new horizons for understanding health and chronic diseases. Genetics studies hereditary traits and variations in DNA structure, while epigenetics examines changes in gene activity that do not alter the DNA sequence itself. One of the key aspects of epigenetics is that these changes can be reversible. This opens up new opportunities for developing treatments for diseases where changes in gene expression play a crucial role, such as autoimmune diseases, cancer, or metabolic disorders. Moreover, epigenetic modifications can be passed from parents to offspring, influencing the health of future generations. Understanding the mechanism of epigenetic regulation presents new prospects in medicine, particularly concerning the impact of the environment, nutrition, and lifestyle on health.
Genetics and Epigenetics
Epigenetic modifications can be inherited from generation to generation, but unlike genetic mutations, they are reversible. Let’s explore the differences between epigenetics and genetics, and why understanding epigenetic processes is so important in treating chronic diseases.
- Epigenetics studies changes in gene activity without altering the DNA sequence. These changes regulate which genes are active and which are not, and can be triggered by environmental factors, lifestyle, or stress.
- Genetics examines heredity and gene variations, explaining how information in DNA is transmitted from parents to offspring and influences the development of an organism. Think of genetics as the architecture of a building with a fixed structure embedded in our genetic code.
If genetics is the structure of the building, then epigenetics represents changes inside, such as turning on lights (active genes) or closing rooms (inactive genes). The building (genetic code) remains unchanged, but its utilization is regulated by epigenetic mechanisms throughout life.
Mechanisms of DNA Regulation:
The main mechanisms of epigenetic regulation of DNA include DNA methylation, histone modifications, and the action of non-coding RNAs. These processes control gene activity, influencing the development and functioning of cells.
- DNA methylation is the process by which methyl groups are added to DNA. These marks act like switches: when they attach to specific regions of DNA, the activity of corresponding genes is suppressed, effectively “turning them off.”
- Histone modifications refer to histones, which are proteins around which DNA is “wrapped.” If we think of DNA as a thread, histones are the spools it is wound around. Modifying histones alters the density of this “winding,” affecting which genes are active and which remain inactive. Acetylation of histones, in particular, weakens the binding between DNA and histones, promoting gene activation.
- Non-coding RNA is a special type of RNA that does not participate in protein synthesis but regulates gene activity, helping cells determine which proteins need to be produced.
DNA methylation is often highlighted as a key mechanism of epigenetic regulation, as it directly impacts gene activity and is associated with numerous diseases. Therefore, we will primarily focus on methylation moving forward.
Factors Influencing Epigenetics
These factors can cause both positive and negative changes in gene expression, potentially leading to a predisposition to various diseases.
- Timing of Exposure:
- Epigenetic changes are particularly sensitive to exposure at specific developmental stages, such as prenatal development, adolescence, and pregnancy.
- The most significant changes occur during critical periods of gene reprogramming, such as early pregnancy and the formation of germ cells.
- Environmental Factors:
- Environmental pollution (mold, chemicals such as endocrine disruptors, pesticides, and heavy metals).
- Exposure to physical factors (radiation, nutrition, stress).
- Biological factors (viruses, bacteria, toxins released by microorganisms).
- Nutrients:
- Nutritional components such as vitamins, minerals, carbohydrates, fats, and proteins play an important role.
- The overall caloric intake and diet also influence epigenetic processes.
Next, we will delve deeper into each of these factors.
Critical Periods of Development for Epigenetic Markers
Epigenetic changes, such as DNA methylation and demethylation, occur during specific critical periods when the organism is most susceptible to changes. These moments are vital for the adaptability and plasticity of the organism, and their impact on health can be long-lasting.
- Early Pregnancy (Conception and Embryonic Development):
- Immediately after fertilization, the first wave of demethylation occurs. The paternal DNA marks are lost more rapidly than those of the maternal DNA.
- Mobile DNA elements partially evade the complete removal of marks.
- During organ formation, the marks change according to their location in the body, determining gene activity in various tissues.
- Intrauterine Period: In germ cells, a second wave of reprogramming occurs, during which old marks are erased and re-established based on the sex of the fetus.
- Puberty: Significant changes in marks influence the development of sexual traits and hormonal regulation.
- Pregnancy: In women, marks can change under the influence of hormones and the environment, affecting the genes of both the mother and the developing fetus.
- Aging: With age, there is a general decrease in methylation levels, increasing vulnerability to diseases associated with epigenetic changes, such as cancer and brain diseases.
These critical periods are important for long-term changes in markers. It is essential to understand that adverse exposures (mold, heavy metals, stress, poor nutrition) during these times can lead to an improper rewriting of marks, increasing the risk of chronic diseases.
Physical Influences on Epigenetics
Physical influences on epigenetics significantly impact health and the development of diseases. Let’s examine several key factors that can alter epigenetic marks and, consequently, gene functioning:
- Behaviour and Stress: Stress and behaviour can change DNA methylation, affecting gene function. For example, individuals who experienced trauma in childhood show increased methylation of certain genes, which is associated with heightened stress responses and a greater propensity for anxiety and depression later in life.
- Radiation: Even low doses of ionizing radiation can alter epigenetic marks. This effect is observed not only in the irradiated cells but also in surrounding cells (bystander effect). This can lead to genomic instability and the transmission of mark alterations to offspring.
- Nutrition: A diet rich in antioxidants (e.g., vitamins C, E, and other substances) can reduce negative epigenetic changes caused by radiation and lower errors in the transmission of genetic information from parents to their offspring.
Chemical Influences on Epigenetics
Chemical exposures can have serious health impacts and can alter gene expression. Let’s explore the primary chemicals capable of influencing epigenetic mechanisms:
- Bisphenol A (BPA) and Phthalates: These substances are commonly found in plastics, packaging, cosmetics, and many household products. Research has shown that BPA exposure during development can cause DNA hypomethylation, negatively impacting gene expression.
- Heavy Metals: Metals such as lead, cadmium, nickel, and others significantly affect the epigenome, particularly during critical developmental periods.
- Alcohol: Ethanol can induce epigenetic changes, especially during early development. Prenatal alcohol exposure leads to gene hypermethylation, which is linked to fetal alcohol syndrome.
- Pesticides: Pesticides and other environmental pollutants can also cause epigenetic changes. Some studies have indicated that these chemicals can affect DNA methylation and alter the expression of genes related to the immune system and cancer development.
Biological Factors Influencing Epigenetics
Biological factors such as viruses, bacteria, and toxins produced by microorganisms can significantly alter gene expression without changing the DNA structure, affecting health and the risk of chronic diseases.
- Viruses:
- Herpesviruses: The integration of their DNA into the host genome can disrupt methylation, increasing cancer risk.
- Human Papillomavirus (HPV): Integration of HPV into the genome can lead to hypomethylation and activation of oncogenic pathways.
- Hepatitis B Virus: This virus induces changes in methylation, which are associated with an increased risk of liver cancer.
- Epstein-Barr Virus (EBV): Alters histone acetylation, facilitating the activation of latent viral genes and disrupting cell cycle regulation.
- Bacteria:
- Helicobacter pylori: Alters DNA methylation in the stomach, increasing cancer risk.
- Streptococcus pneumoniae: Affects the expression of immune response genes, reducing the efficacy of immune cells.
- Endotoxins:
- Escherichia coli: Lipopolysaccharides affect methylation, causing chronic inflammation and potential cancer.
- Klebsiella pneumoniae: Contributes to changes in methylation and may be linked to inflammatory diseases.
- Pseudomonas aeruginosa: Can induce epigenetic changes affecting immune response and DNA methylation.
- Mycotoxins:
- Aspergillus: Produces aflatoxin, which causes hypomethylation and liver cancer.
- Stachybotrys chartarum: Releases toxins such as satratoxin, trichothecenes, and stachybotryins that impact epigenetics. These mycotoxins can alter DNA methylation, causing both hypo- and hypermethylation, disrupting gene expression, and increasing the risk of chronic diseases and cancer.
- Gut Dysbiosis:
- Pathogenic Bacteria (Clostridium difficile and Escherichia coli): Excessive amounts of these bacteria lead to hypomethylation of immune response genes, disrupting immune regulation and causing chronic inflammation, increasing the risk of diseases, including cancer.
- Candida albicans: Its influence on DNA methylation leads to changes in gene expression, increasing disease risk, including cancer, by altering regulators responsible for apoptosis. Hypomethylation can activate genes that promote the survival of tumour cells.
- Decreased Microbiota Diversity: Reduced diversity disrupts the microbial balance and causes epigenetic changes, increasing inflammation and disease risk. This can result in hypomethylation of protective genes, making the organism more vulnerable.
Conclusion
Thus, the study of genetic and epigenetic mechanisms allows for a deeper understanding of how environmental factors and lifestyle choices influence gene activity and, ultimately, our health. Epigenetic changes, such as DNA methylation and histone modifications, play a key role in the predisposition to various diseases, including cancer and inflammatory processes. Recognizing the significance of critical developmental periods and the impact of different factors can aid in the development of strategies for the prevention and treatment of chronic diseases. Given that epigenetics offers the possibility of reversible changes, it opens the door to new approaches in therapy and personalized medical care, which can ultimately lead to more effective and safer treatment methods. In the second part of the article, we will discuss the currently available pathways to influence epigenetics.