Picture by IChemE Institution of Chemical Engineers
In this brief school paper, I presented a basic introduction to the role of gene expression and environmental factors in human life experience and the understanding of disease. Epigenetics is an incredible field to be in. If I could start all over again and be twenty years younger, this is what I would study. But, my life path soon approaching midlife has something else in store for me. However, I want to be an inspiration to young souls out there who have every chance in the future to shape it and make human history happen. I share to inspire young minds to follow their dreams, to be resilient in their pursuit of knowledge, to not let fear get in the way of achieving greatness, and to never cease learning. Passion for learning will take you very far in life, thus, be open to expand your understanding of life and the world at all times. This is my advice to any young soul reading this short article of mine who finds himself or herself hungry for a life full of meaning and purpose. This is for you, young spirits ready to take onto the future of the world.
Gene Expression and Environmental Factors In Human Life Experience and The Understanding of Disease A Basic Introduction Carmen A. Kraela PSY 220 September 26, 2021
As presented by Randy Jirtle, a geneticist in the Department of Radiation Oncology at Duke University, who answered several questions in 2007 related to epigenetics and how our lifestyles may affect health, one of the questions he answered was “If environmental factors can influence the gene expression in offspring, can that process be reversed or altered by other factors (diet, drugs, gene therapy, etc.) after the offspring are born?” (Nova Science Trust, 2007, Q6). Mr. Jirtle claimed that “during early fetal development, maternal nutrient supplements of methyl-donating substances (folic acid, choline, vitamin B12, and betaine) or genistein, found in soy products, can counteract the reduction in DNA methylation caused by BPA.” (Nova Science Trust, 2007, Q6). BPA is an industrial chemical used for making certain types of plastics and resins since the 1950s. One of the concerns related to BPA, which per an article on the subject published by The Mayo Clinic, exposure to BPA can lead to health concerns due to this industrial chemical being able to sip though plastic in food or beverages. The reason this is potentially dangerous is because of the impact this could have on health, if indeed the research which suggests that a link between BPA and blood pressure, type 2 diabetes, and cardiovascular disease in fact exists. (Bauer, 2021)
The first lesson most valuable to my life from my studies in Developmental Psychology taught me that the fundamental basis of human life experience is rooted in both nature and nurture but my understanding of the role of epigenetics at molecular level in both of these was much further expanded by my current studies in Biological Basic of Behavior. In Chapter 4, of Epigenetics and human health: linking hereditary, environmental and nutritional aspects, (2009), author Alexander Haslberger illustrates nurture vs. nature, as “Hereditary dispositions and environmental factors such as nutrition and the natural and societal environment interact with human health. Diet compounds raise increasing interest due to their influence in epigenetic gene expression. Nutrition and specific food ingredients have been shown to alter epigenetic marks such as DNA methylation or histone acetylation involving regulation of genes with relevance for fundamental mechanisms such as antioxidative control, cell cycle regulation or expression of immune mediators.” (Halsberger, 2009, Chapter 4) This chapter also explains how modification of gene expression is possible by altering chromatin without changing the DNA sequence and how this additional regulatory molecular level exists in addition to the genetic code in mammalian cells. Nutrition and lifestyle factors influence chromatin packaging where the epigenetic changes occur, which is correlated to the development of chronic diseases like cancer, diabetes, and obesity. Thus, clearly, there is a powerful interconnection between environmental factors and lifestyle, including nutrition, and the epigenome which Halsberger describes in his book as “a cell’s overall epigenetic state.” (Halsberger, 2009, Chapter 4.2) A great study which showcases the environment’s impact on alterations to a cell’s epigenetic makeup, is shown in the study of monozygotic twins which are epigenetically identical early in life but, with age, exhibit substantial differences in the epigenome in later years of life. (Halsberger, 2009, Chapter 4.2) What this clearly illustrates is that environmental factors and lifestyle influence gene alterations. The study goes on to explain the importance of maternal diet in prenatal care and the life of an embryo. Going back to the bisphenol A (BPA) mentioned earlier, Halsberger remarks that “maternal diet containing bisphenol A (BPA), an estrogenic monomer used in polycarbonate plastic production, significantly decreases the offspring’s methylation of the Avy gene promoter which induces a different phenotype. Maternal nutritional supplementation with methyl-donors counteracts the effects from BPA, showing that simple dietary changes may protect against harmful epigenetical effects caused by environmental toxins.” (Halsberger, 2009, Chapter 4.4.1) Knowing this, it’s easy to understand how early epigenetic programming may be alterable through the mother’s diet during pregnancy; however, we have to understand that impact on human health is directly linked to influences from the natural and social environment, from things like pollution and toxins to dietary factors.
Per Halsberger, “Air pollution, for instance, particular matters/small particles in the air and cigarette smoke, appear to have omnipresent toxicological influences on humans. Promoter hypermethylation in early tumorgenesis is likely to have a clinical importance, because dissentient promoter methylation in tumor suppressor genes has been detected in a large percentage of human lung cancers.” To truly understand this statement one would have to understand DNA methylation. A brilliant description of it was provided by Mihai Niculescu and Paul Haggarty in their book Nutrition in Epigenetics (2011) which states, “DNA methylation was first described as a natural chemical modification in 1950 (Wyatt, 1950), but its relationship with DNA activation remained unclear until 1971 when de Waard demonstrated that the biological activity of DNA was modulated by its methylation in vitro (de Waard, 1971). Soon it became clear that DNA methylation was a dynamic process that varied across different phases of the cell cycle, and that the amount of DNA methylation might be related to the active and inactive states of chromatin (Comings, 1972). The role of DNA methylation in regulating gene expression was clearly hypothesized by Venner and Reinert in 1973 (Venner and Reinert, 1973). The idea that DNA methylation could profoundly influence gene expression led to the hypothesis that the inactivation of chromosome X was epigenetic (Riggs, 1975), and the opposite relationship between DNA methylation and gene expression was established later (Christman et al., 1977). […] In 1964, both methylation and acetylation of histones were reported to have a role in RNA synthesis (Allfrey et al., 1964). (Niculescu & Haggarty, 2011, Chapter 1.1)
When we consider dietary effects, studies of dietary effects on epigenetic gene regulation are still in their infancy but some research has already provided answers. “Evidence shows that a diet rich in vegetables and fruits may prevent some kinds of cancers [65]. In this context, the role of flavonoids is often discussed. Flavonoids can act either in a pro- or antioxidative manner depending on their structure and characters. Because of the antioxidative properties of some flavonoids, oxidative damage of DNA can be prevented and cancerogenesis altered.” (Halsberger, 2009, Chapter 4.4.2) Chapter four of Halsberger’s book concludes with an important summary, which states that “Genomics and World Health (WHO, Geneva, 2002) underlined that ‘Except for genetic diseases that result from a single defective gene, most common diseases result from environmental factors, together with variations in individual susceptibility, which reflect the action of several genes. Further research should lead to the discovery of specific molecular targets for therapy, provide information that will allow treatment to be tailored to individual needs, and, in the longer-term, generate a new approach to preventive medicine based on genetic susceptibility to environmental hazards.’” (Halsberger, 2009, Chapter 4.7)
Going back to the question presented at the beginning of my essay, “If environmental factors can influence the gene expression in offspring, can that process be reversed or altered by other factors (diet, drugs, gene therapy, etc.) after the offspring are born?” I believe that Haslberger answers this question by showing evidence in his book of how when we speak of disease we are either dealing with defective genes or environmental factors altering genes. When looking at one of the world’s most challenging diseases such as cancer, “A number of studies provide evidence that some natural bioactive compounds found in food and herbs can influence gene expression via modulation of the DNA methylation process. It has been demonstrated that some polyphenols (i.e., catechins, quercetin, myricetin, genistein, resveratrol) and vitamins (i.e., retinoic acid, vitamin D3) exert a profound inhibitory effect on DNA methyltransferase enzyme activity and/or DNA methyltransferase gene expression and contribute to reactivation of methylation-silenced tumor suppressor genes in cancer cells leading to blocking of cancer development.” (Halsberger, 2009, Chapter 11)
Furthermore, “A common observation in cancer is epigenetic change consisting of altered methylation of DNA and the histones associated with DNA. These changes occur early in the development of the disease and the pattern of methylation correlates with cancer stage (Szyf et al., 2004). More interesting is the possibility that widespread epigenetic change in normal cells may actually be causal in the transition to cancer and that nutrition may influence this process.” (Niculescu & Haggarty, 2011, Chapter 1.3) The study of epigenetics has it’s many challenges, one in particular which remains a problem to be solved revolves around the fact that establishing the causality between nutrition, epigenetics, and health is complex in human studies where much of the evidence arises from observational designs as experimentation can turn unethical. As, however, described by Niculescu and Haggarty, there is hope. “Modulation of epigenetic status can occur throughout the life course, it has been implicated in the etiology of disease, it is modifiable by diet and lifestyle, and it may even be passed between the generations. The promise of this emerging field is that the study of epigenetics and nutrition may help to elucidate the way in which nutrition interacts with the genome to influence human health.” (Niculescu & Haggarty, 2011, Chapter 1.4)
References:
Nova Science (2007). Epigenetics: Expert Q&A. PBS Online.
Bauer, A., Brent (M.D.), (2021, May 14) Mayo Clinic. Healthy Lifestyle Nutrition and Healthy Eating. What is BPA, and what are the concerns about BPA?
Haslberger, Alexander. (2009) Epigenetics and Human Health: Linking Hereditary, Environmental and Nutritional Aspects. Weinheim: Wiley-VCH, 2009. Web.
Niculescu, Mihai D., and Paul. Haggarty. (2011) Nutrition in Epigenetics . Ames, Iowa: Blackwell, 2011. Print.
Everything I do serves to honor my human life and the God who gifted me with it. It humbles me greatly and never ceases to amaze me, learning about the delicate nature by which the very makeup of my complex anatomy points to the mastery of God's science and art. Though most scientists would dislike me for using the word God, I choose to do so deliberately. At the end of life, thus, I shall have no regrets. I had immense love of art and love of science and I attributed both to what I chose to believe in, the God I loved. If that makes me foolish, then I am a beautiful dreamer with an extraordinary imagination. If that makes me righteous, then I am a beautiful dreamer with an extraordinary imagination and I get to someday meet God. - Carmen A. Cisnadean
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