What is Epigenetics?

When we think about genes -- i.e. the heredity units that play a large part in determining our individual characteristics -- many of us tend to think of them as rigid units passed down from generation to generation, impervious to the influences of the environment.

While the DNA sequence you inherit certainly plays an important role in your genome, helping to determine which genes are expressed and which ones are not, it’s not the only factor that influences how your genes behave.  

Instead, epigenetic researchers have found that numerous environmental factors can potentially change the behavior of your genes, resulting in a stimulus-dependant up or down-regulation in the expression of certain genes.

So what kind of exogenous factors can actually influence these kinds of changes and what might the ultimate consequences be?  Well, before we dive too far down that rabbit hole, let’s first discuss in more depth what epigenetics is and how it works.  

What is Epigenetics?

Within the field of biology, epigenetics involves the study of hereditary alterations in gene expression that occur in the absence of any such changes occurring in a person’s DNA sequence.⁽¹⁾

In simple terms, epigenetic changes, which come about by environmental factors, can actually switch different genes on or off.  While you may be born with a specific DNA sequence that influences the behavior of your genes, external factors can actually change how they behave, leading to potential alterations that can be passed on from one generation of cells to the next.  

Research suggests that epigenetic changes in gene expression occur by way of a three-step process.⁽²⁾ In step one, something in your environment activates a switch in your DNA. 

In the second step, the turned-on switch initiates a process in which new proteins or messenger are sent out. Finally, as the environmental stimulus continues, the switch learns to stay activated, helping to maintain the epigenetic changes that occurred. 

Mechanisms of Epigenetic Change

Researchers have been interested in identifying the different mechanisms through which epigenetic changes occur for some time, and to date, it appears that there are at least three different pathways through which exogenous factors can potentiate change: DNA methylation, histone modifications, and micro RNA expression.  

1. DNA Methylation

One way in which researchers have found that epigenetic change can occur is through DNA methylation, which refers to the physiological process through which a methyl group is added to a particular strand of DNA.  

Modifying the structure of a specific strand of DNA through methylation can ultimately change the behavior of the associated gene, oftentimes inhibiting the transcription process, thus turning the gene off.⁽³⁾⁽⁴⁾

2. Histone Modifications

Another way in which epigenetic alterations can occur is through histone modifications.  Histones are proteins that play an important architectural role in chromatin, a complex molecular assembly within a chromosome that acts as the reel in which DNA is wrapped around.⁽⁵⁾

When histones are altered, it can change the structure and arrangement of chromatin, potentially altering the transcription process of a particular gene.  Histone modifications can both turn a gene on or off, depending on how the chromatin is altered -- In instances in which the chromatin of a particular cell is condensed, it becomes inactive and transcription is turned off, whereas expanding a previously condensed chromatin may activate transcription.⁽⁶⁾

3. Micro RNA Expression 

MicroRNA (miRNA) is a type of non-coding ribonucleic acid (RNA) that goes through the DNA transcription process but ultimately does not get translated into proteins.⁽⁷⁾

When it comes to epigenetics, research suggests that exogenous factors can cause miRNAs to interfere with the normal functions of messenger RNAs -- a type of RNA that transfers genetic information from DNA to a ribosome -- leading to a down-regulation in the expression of certain genes.⁽⁸⁾

Epigenetics and the Role of the Environmental

Numerous studies have examined how exposure to environmental chemicals affects epigenetics, with many investigations focused on the relationship between epigenetic changes and disease susceptibility.⁽⁹⁾

In-vitro experiments involving both human and animal cells have demonstrated that exposure to a number of different heavy metals and air pollutants such as arsenic, chromium, cadmium, black carbon, particulate matter, and benzene can cause significant changes in genome function that can, in turn, increase the risk of adverse health outcomes.⁽¹⁰⁾

Inflammation and Epigenetics 

There is an ample body of evidence to suggest that exposure to environmental toxins can cause significant alterations in immune cell activation.  

In addition to blunting the immune response, these alterations have also been shown to upregulate the expression of certain pro-inflammatory genes, which can, in turn, lead to a number of inflammatory diseases like cancer, metabolic syndrome, diabetes, and arthritis along with lung and heart disease.⁽¹¹⁾

A number of studies involving epigenetics and cancer, for instance, have demonstrated the role of histone modification in cancer-related tumor growth.  More specifically, alterations to histones H3 and H4, which can be spurred on by environmental exposures, have been shown to turn off certain genes that have tumor-suppressing qualities.⁽¹²⁾

There is also evidence that miRNA may play an important tumor-suppressing function as well, with some studies demonstrating a relationship between epigenetic alterations and the downregulation of miRNA subgroups in tumors.⁽¹³⁾

Epigenetics and Obesity

Other research suggests that environmental exposures -- particularly those that occur early in life -- can lead to changes in the epigenome that persist over the life course and increase the risk of obesity.⁽¹⁴⁾

Compared to research on epigenetics and cancer, however, the particular pathways through which environmental factors affect obesity are less clear.  With that being said, researchers have observed that certain environment-induced changes in gene expression can lead to alterations in things like appetite, satiety, and metabolism which can, in turn, make maintaining a healthy weight more difficult, especially as you age.⁽¹⁵⁾

Improving Your Epigenetics Through Lifestyle Changes

While environment-induced epigenetic changes can lead to a whole host of negative health outcomes like cancer and obesity, more and more research is also beginning to suggests that you may be able to overturn unfavorable epigenetic changes through lifestyle intervention.  

In other words, although environmental factors can negatively impact the function of your epigenome, you may also be able to change your epigenetics for the better simply through making alterations to the way you live.  

Nutrition and Epigenetic Change 

Scientists in the subfield of nutriepigenomics are continuing to explore the relationship between nutrition and epigenetic modifications and to date, there is a sizeable body of evidence that you may be able to reverse certain unfavorable gene alterations through the foods that you consume in your diet.⁽¹⁶⁾

More specifically, evidence from multiple trials suggests that exposure to certain dietary cues may lead to positive alterations in gene expression, which in turn may help to improve your overall health and reduce the risk of diseases like cancer and metabolic syndrome.⁽¹⁷⁾

For example, one 2010 study published in the European Journal of Pharmacology ultimately found that exposure to polyphenols such those present in green tea (EGCG), grapes (resveratrol), and soybeans (genistein) helped to reverse the silencing of tumor-suppressor genes, reducing the overall risk of uncontrolled cell growth (cancer).⁽¹⁸⁾

Other research has demonstrated that certain substances found in apples -- and particularly in apple extract -- may also help to positively alter the epigenome.  Findings suggest that apple-derived substances like catechins, epicatechins, chlorogenic acid, and quercetin may help to increase leptin production by altering methylation on certain regions of DNA (CpG sites).⁽¹⁹⁾

An increased leptin production, in turn, has been shown to aid in the prevention of weight gain and the improvement of several markers of metabolic syndrome, including insulin resistance and hyperglycemia.  In the aforementioned study, the researchers ultimately found that regular supplementation with apple extract helped to significantly reduce the occurrence of diet-related obesity.⁽²⁰⁾

The Importance of Micronutrients 

Several vitamins and minerals have also been shown to affect gene expression, with deficiencies potentially disrupting the normal function of your genome.  Evidence suggests that deficiencies in things like B vitamins, vitamin D, and iron just to name a few, can lead to a number of different negative health outcomes.^(21)(22)

More specifically, research shows that micronutrient supplementation, particularly in instances of deficiency, may help to regulate gene expression in the post-transcription stage through positively impacting miRNA expression -- again, micro RNA can sometimes interfere with messenger RNA, resulting in the downregulation of a particular gene.⁽²³⁾

Epigenetic Change and Exercise

On top of your diet, science suggests that regular exercise may also help to induce positive epigenetic changes as well.  For example, research shows that individuals with a family history of type 2 diabetes, on average, have significantly lower maximal aerobic capacities (Vo2max) in comparison to those with no family history, even when both individuals have similar levels of physical activity.⁽²⁵⁾

However, on top of seeing significant reductions in things like waist circumference, body weight, and BMI through exercise-induced epigenetic changes, research has also demonstrated that those with a family history of type 2 diabetes, may also be able to improve their Vo2max through epigenetics as well.  

For example, one 2012 study published by the American Diabetes Association, ultimately found that following a 6-month exercise program, those with a family history of type two diabetes not only saw significant reductions in body weight along with several markers of metabolic syndrome, but they also saw significant improvements in their Vo2max.⁽²⁶⁾

The researchers ultimately attributed these improvements in aerobic capacity to a positive alteration in DNA methylation in the NDUFC2 gene, which plays an important role in respiratory function.   

Wrap Up

Epigenetics refers to the basic concept that certain environmental factors can influence the behavior of your genes without affecting any change in your DNA sequence.  

Research suggests that exposure to several environmental chemicals and heavy metals can alter your epigenome, changing the expression of your genes and increasing the risk of several diseases including cancer and obesity.  

While environmental factors can alter your genetics for the worse, mounting evidence also suggests that you may be able to reverse certain epigenetic changes through your lifestyle.  More specifically, recent evidence has demonstrated that altering your diet and fitness routine may help to improve to function of your epigenome.

• References
  1. “Environmental epigenetics”Bollati, V., Baccarelli, A. Heredity. Feb. 2010.
  2. “An operational definition of epigenetics”Berger, S.L., Kouzarides, T., Shiekhattar, R., Shilatifard, A. Genes and Development. Apr. 2009.
  3. “Environmental epigenetics”Bollati, V., Baccarelli, A. Heredity. Feb. 2010.
  4. “Epigenetics in Cancer”Esteller, M., The New England Journal of Medicine. Mar. 2008.
  5. “Making sense of chromatin states”Baker, M. Nature Methods. Aug. 2011.
  6. “Environmental epigenetics”Bollati, V., Baccarelli, A. Heredity. Feb. 2010.
  7. “Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression”Baker, M. Nature Methods. Aug. 2011.
  8. “MicroRNAs as Oncogenes and Tumor Suppressors”Chen, C.Z. New England Journal of Medicine. Oct. 2005.
  9. “Environmental epigenetics”Bollati, V., Baccarelli, A. Heredity. Feb. 2010.
  10. “Epigenetics and environmental chemicals”Baccarelli, A., Bollati, V. Current Opinion in Pediatrics. Apr. 2009.
  11. “Epigenetics of Inflammation, Maternal Infection, and Nutrition”Claycombe, K.J., Brissette, C.A., Ghribi, O. The Journal of Nutrition. May. 2015.
  12. “Epigenetics in Cancer”Esteller, M., The New England Journal of Medicine. Mar. 2008.
  13. “MicroRNAs as Oncogenes and Tumor Suppressors”Chen, C.Z. New England Journal of Medicine. Oct. 2005.
  14. “Epigenetics and human obesity”van Dijk, S.J., Molloy, P.L., Varinli, H., Morrison, J.L., Muhlhausler, B.S. International Journal of Obesity. Feb. 2014.
  15. “Genetics and epigenetics of obesity”Herrera, B.M., Keildson, S., Lindgren, C.M. Maturitas. May. 2011.
  16. “Nutriepigenomics: the role of nutrition in epigenetic control of human diseases”emely, M., Stefanska, B., Lovrecic, L., Magner, U., Haslberger, A.G. Current Opinion in Clinical Nutrition. 2015.
  17. “Nutriepigenomics: the role of nutrition in epigenetic control of human diseases”emely, M., Stefanska, B., Lovrecic, L., Magner, U., Haslberger, A.G. Current Opinion in Clinical Nutrition. 2015.
  18. “Hypomethylation and induction of retinoic acid receptor beta 2 by concurrent action of adenosine analogues and natural compounds in breast cancer cells”Stefanska, B., Rudnicka, K., Bednarek, A., Fabianowska-Majewska, K. European Journal of Pharmacology. Jul. 2010.
  19. “Nutriepigenomics: the role of nutrition in epigenetic control of human diseases” Stefanska, B., Lovrecic, L., Magner, U., Haslberger, A.G. Current Opinion in Clinical Nutrition. 2015.
  20. “Prevention of diet‐induced obesity by apple polyphenols in W istar rats through regulation of adipocyte gene expression and DNA methylation patterns”Boque, N., de la Iglesia, R., de la Garza, A.L., Milagro, F.I., Olivares, M., Banuelos, O., Soria, A.C., Rodriguez-Sanchez, S., Martinez, J.A., Campion, J. Molecular Nutrition Food Research. Mar. 2013.
  21. “Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging”Wimaiawansa, S.J. Biology. Feb. 2019.
  22. “Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation”Anderson, O.S., Sant, K.E., Dolinoy, D.C. The Journal of Nutritional Biochemistry. Aug. 2012.
  23. “The role of vitamins and minerals in modulating the expression of microRNA”Beckett, E.L., Yate, Z., Veysey, M., Duesing, K. Nutrition Research Reviews. Jun. 2014.
  24. “A Family History of Diabetes Is Associated With Reduced Physical Fitness in the Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia Study”Isomaa, B., Forsen, B., Lahti, K., Holmstrom, N., Waden, J., Matintupa, O., Almgren, P., Eriksson, J.G., Lyssenko, V., Taskinen, M.R., Tuomi, T., Groop, L.C. Diabetologia. Aug. 2010.
  25. “Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise"Sharples, A.P., Stewart, C.E., Seaborne, R.A. Aging Cell. Apr. 2016.
  26. “Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes"Nitert, M.D., Dayeh, T., Volkov, P., Elgzyri, T., Hall, E., Nilsson, E., Yang, B.T., Lang, S., Parikh, H., Wessman, Y., Weishaupt, H., Attema, J., Abels, M., Wierup, N., Almgren, P., Jansson, P-A., Ronn, T., Hansson, O., Eriksson, H-F., Groop, L., Ling, C. American Diabetes Association. Dec. 2012..