By Parmida Pajouhesh, Neurobiology, Physiology & Behavior ‘23

Author’s Note: For as long as I can remember I wanted to attend medical school and become a pediatrician. More recently, I have been exposed to the study of epigenetics, which has unveiled the importance of prioritizing prevention of disease and furthered my interest in the field of medicine. In hopes of practicing internal medicine in the future, I wanted to investigate how providing care and support to the patient on an individualized level is crucial for effective treatment in the long term. 

Put simply, epigenetics means “on top of” genetics, derived from the Greek prefix “epi.” Epigenetics describes the relationship between one’s gene activity and their environment, whereby the activity of the genes is altered but the DNA sequence is not directly modified. Genes can be turned “on” or “off” and changes to our epigenome are fortunately reversible. Researchers studying this phenomenon have been trying to answer the following questions: how does our knowledge of epigenetics help to further advance the study of illness and disorders, such as cancer and schizophrenia? How can understanding this phenomenon help scientists, doctors and researchers provide personalized care for patients?

Epigenetic changes, which impact our phenotype without directly affecting our genotype, have been previously tied to aging, our environment and even lifestyle [1]. Prenatal and early postnatal environmental factors have influenced an offspring’s risk and vulnerability to developing a health condition [2]. For instance, in the 1940s, children who were born during a period of increasing famine had exceedingly greater rates of coronary heart disease after maternal exposure to famine, as opposed to those not exposed. This was linked to a decrease in DNA methylation—an epigenetic alteration—of the gene responsible for insulin growth [2]. 

These epigenetic modifications continue to take place throughout an individual’s lifespan. Exposure to pollution can alter methyl tags on DNA and make an individual even more susceptible to neurodegenerative diseases [3]. The foods we consume can have an impact on our epigenome; one study has shown that a high-fat, low-carb diet could open up chromatin and thus improve mental ability [1]. 

A closer look into our epigenome

Common and widely studied epigenetic alterations include histone modifications and DNA methylation. These mechanisms regulate the expression of genes as well as “cellular and biological functions related to homeostasis, allostasis and disease” [4]. DNA methylation adds a methyl group (-CH3) to cytosine at a promoter region containing repetitive sequences of CpG (cytosine–phosphate–guanine) dinucleotides. Proteins then bind to the methylated CpG islands, which correlates with transcriptional repression and affects gene expression [4]. This form of methylation has been previously linked to cancer [5]. 

As for the modification of histones, ubiquitin—a molecule which is attached to a protein destined for degradation—has been linked to neurological disorders including Parkinson’s disease and Angelman syndrome [5]. Likewise, histone methylation has been linked to several biological processes: DNA repair, stress responses, development, differentiation and aging [4]. If any one of these processes is altered, whereby histone methylation is either activated or inhibited, this can result in the development and progression of disease. For example, H3K4me2, a post-translational dimethylation at the lysine 4 residue of the histone H3 protein, located at the promoter of active genes, is downregulated in cases of lung, kidney, prostate and pancreatic cancers [6]. Histone modification contributes to the cell cycle, growth, DNA replication and other processes. Therefore, abnormal histone modifications can lead to the development and progression of tumors [6]. 

Personalized medicine and targeted care

Inevitably, individuals are prone to changes in their epigenome, which makes providing targeted care an even more challenging task. These changes occur not only between individuals but also within a single individual over time. Therefore, genomic approaches that include identifying specific variations in DNA and RNA sequences can help to bridge the gap between epigenetics and personalized care. Health care professionals have shifted their attention towards diagnostic tests that use genomic data to more accurately assess the extent of a patient’s risk for disease or illness, to determine appropriate dosage amounts and to make conclusions about the benefits of a specific drug or treatment. According to a study by Mahmood Rasool that highlights epigenetics as a contributing factor to personalized and individualized care, “various factors such as nutrition, age, body weight, sex, genetic behavior, infections, co-medications and organ function are important considerations that are unavoidable during the course of treatment for a disease” [4]. 

Combatting epigenetic changes. What’s next?

Changes due to our environment are unpredictable; therefore, we must take precautions as early as possible. Being wary of how our lifestyle can impact the activation of our genes is crucial to our health and development. We must take preventative measures early in our life and determine which lifestyle changes will benefit us in the long term. Exposure to hazards in our environment is not fully noticeable until years and sometimes decades later. If we place emphasis on the prevention of disease early on, we are much less likely to encounter abrupt and irreversible effects to our well-being. While epigenetic biomarkers are being evaluated for use in environmental risk assessment, more immediate lifestyle changes include reducing exposure to harmful air pollutants, implementing specific dietary changes and altering medication use that will provide long-term benefits, as opposed to only short-term relief [4]. Our diet can result in profound changes in our epigenome, leading to human disease. For instance, lacking essential amino acids in your diet can result in colon cancer, which “impairs biosynthesis of the active precursor for DNA methylation.” Similarly, exposure to nicotine and other toxins can cause epigenetic changes in smokers, “affecting the genes involved in normal pulmonary function.” Exercise can also have important effects on the skeletal-muscle epigenome [7].

With this being said, we must recognize the importance of integrative medicine in primary care. Physicians, and even specialists, consider the patient as a whole person and are cognizant of their lifestyle, diet, genetic background and even mental health. This holistic approach to medical care provides patients with a greater sense of what they need to accomplish to keep their body and mind healthy. This not only strengthens the connection between practitioner and patient, but it demonstrates the importance of taking preventative measures prior to development of the illness. Understanding epigenetics can increase our awareness of how physical space alters our well-being and reinforce that providing holistic and preventative care reduces the negative impacts of epigenetic changes. 

References (online)

1. Baccarelli, Andrea, and Valentina Bollati. “Epigenetics and environmental chemicals.” Current opinion in pediatrics vol. 21,2 (2009): 243-51. doi:10.1097/mop.0b013e32832925cc
2. Heerboth, Sarah et al. “Use of epigenetic drugs in disease: an overview.” Genetics & epigenetics vol. 6 9-19. 27 May. 2014, doi:10.4137/GEG.S12270
3. Moosavi, Azam, and Ali Motevalizadeh Ardekani. “Role of Epigenetics in Biology and Human Diseases.” Iranian biomedical journal vol. 20,5 (2016): 246-58. doi:10.22045/ibj.2016.01
4. Rasool, Mahmood et al. “The role of epigenetics in personalized medicine: challenges and opportunities.” BMC medical genomics vol. 8 Suppl 1,Suppl 1 (2015): S5. doi:10.1186/1755-8794-8-S1-S5
5. Tollefsbol, Trygve O. “Dietary epigenetics in cancer and aging.” Cancer treatment and research vol. 159 (2014): 257-67. doi:10.1007/978-3-642-38007-5_15
6. Li, Simin, et al. “Association between H3K4 Methylation and Cancer Prognosis: A Meta-Analysis.” Thoracic Cancer, vol. 9, no. 7, 2018, pp. 794–99. Crossref, doi:10.1111/1759-7714.12647.
7. Feinberg, Andrew P. “The Key Role of Epigenetics in Human Disease Prevention and Mitigation.” New England Journal of Medicine, edited by Dan L. Longo, vol. 378, no. 14, 2018, pp. 1323–34. Crossref, doi:10.1056/nejmra1402513.

References (print)

1. Baccarelli and Bollati. Current opinion in pediatrics vol. 21,2 (2009): 243-51. 
2. Heerboth, et al. Genetics & epigenetics vol. 6 9-19. 27 May. 2014.
3. Moosavi and Ardekani. Iranian biomedical journal vol. 20,5 (2016): 246-58. 
4. Rasool, et al. BMC medical genomics vol. 8 Suppl 1,Suppl 1 (2015): S5. 
5. Tollefsbol. Cancer treatment and research vol. 159 (2014): 257-67. 
6. Li, et al. Thoracic Cancer, vol. 9, no. 7, 2018, pp. 794–99. 
7. Feinberg. New England Journal of Medicine, edited by Dan L. Longo, vol. 378, no. 14, 2018, pp. 1323–34.