We often underestimate the power and impact our experiences and quality of life can have on us as human beings, or as living beings at all. In capitalistic societies in particular, the effects of work-induced anxiety, amongst other things, are oftentimes overlooked in order to promote productivity and drive profit. On the long term, this can cause our bodies (and that of our children even) to change without us necessarily noticing it at first hand. And when we finally do, it’s often too late. Likewise, we often ignore how certain demographics owe their genetic makeup to what their ancestors had to go through. So, the same way I approached neuroplasticity in my previous article and linked it to the power we have over ourselves, we will in this article try to understand what epigenetics really consist of and attempt to place it in both a modern-day context as well we in past historical events. Indeed, what happens at a genetic level when we recurrently get expose to certain external factors? Are these modifications always in our advantage? Can epigenetics affect our behavior? Let’s try and find out more about this quite unpopular topic and understand how our life choices and experiences can change us at a genetic level.
So what is epigenetics? Etymologically speaking, epigenetics is the Greek for “in addition to genetics”. In the field of biology, it is the study of inherited phenotypic changes that do not involve DNA sequence alterations. In plain terms, this means the change in characteristic or observable traits in a living organism caused by external factors, and which happens on top of or in addition to the traditional genetic basis for inheritance. Epigenetics thus affect how our genes express themselves. For instance, a particular region on chromosome 15 plays a major role in eye color. Within this same region, the gene OCA2, which produces a protein known as P protein, is responsible for the maturation of melanosomes, which are cellular structures that produce and store melanin. The same melanin that is behind the pigmentation of our skin is in fact also responsible for the color of our eyes. More P protein, and thus higher levels of melanin, means darker eye color (black, brown or hazel for example). Less P protein, and hence lesser levels of melanin, means lighter eye color (grey, blue or green for instance). OCA2 is nevertheless not the only responsible gene for eye color. A range of other genes can also play smaller roles in this respect. Some of those genes are also involved in skin and hair color. This helps us understand what happens on a genetic level for us to have the physical characteristics we have – from hair, to eye color, to skin tone, to overall morphology. Our entire body is in fact coded like a computer program or a website. The same way lines and lines of HTML codes define the appearance of a site on the internet, our appearance is determined by a myriad of genetic sequences. So while a lot of us think of our appearance as the result of a biological lottery between our parents’ genes, think it rather like a very organized script nature wrote for us. This ‘script’ turns out to however be subject to potential changes, and that’s where epigenetics come into play.
In their 2016 article “Prenatal Maternal Stress and Epigenetics: Review of the Human Research”, Lei Cao-Lei, David P. Laplante and Suzanne King explain how a pregnant woman’s stress can have repercussions on the baby at a genetic level, and among others how it can “induce long-lasting effects on offspring outcomes in later life”. In this study, Cao-Lei, Laplante and King explore the association between fetal experience and epigenetic changes, with a particular focus on DNA methylation – a biological process during which methyl groups (an alkyl derived from methane) are added to the DNA molecule and hence contribute to changing the activity of a DNA segment however without changing the sequence. Findings mentioned in the study explain how stress in mothers can result in a decreased protection of the fetus: “stress in the mother not only increases her own circulating cortisol levels but also reduces the activity of the GC barrier enzyme in the placenta, HSD11B2 (11β-hydroxysteroid dehydrogenase 2, which converts noxious maternal cortisol into inactive cortisone before reaching the fetus), leaving her fetus less well protected”. The effects of prenatal maternal stress on the baby however do no stop at birth, as this stress can also result in long-lasting consequences up into puberty and adulthood: “Maternal exposure to a severe stressor, such as environmental pollutants, nutritional factors, psychosocial stress, or maternal depression during pregnancy, can increase the fetus’ risk for suboptimal growth in a wide range of somatic systems, and for developing a variety of disorders in adulthood.” Affected areas in fact include behavior, immune functions and brain development. Cao-Lei, Laplante and King close their study with the conclusion that in-utero exposure to environmental stress via the mother visibly results in long-term epigenome alterations in the baby. Similarly, another study explored the link between early-life exposure to severe famine, higher methylation level in the IGF2 gene and epigenetic changes. The findings showed that experiencing sever famine in the early years of life caused an increase in methylation levels and was associated with higher total cholesterol levels in late adulthood.
Indeed, epigenetic changes can also be observed transgenerationally. That is to say, that information can be passed on genetically from one individual to their offspring, and that the trauma that that person could have experienced can therefore influence the genetic expression in their offspring. A growing body of research has in fact explored the transgenerational effects in mental health disorders and response behaviors amongst Holocaust survivors and their descendants. The findings showed epigenetic modifications of a glucocorticoid receptor gene, Nr3c1. Glucocorticoid being a regulator of the hypothalamus-pituitary-adrenal axis and known to affect stress responses, Holocaust survivors’ offspring were therefore found to be more prone to higher stress and anxiety, including increased symptoms of PTSD, greater risk of developing generalized anxiety disorder, and higher levels of cortisol (stress hormone). Another study published in the journal of Biological Psychiatry studied the epigenetic effects caused by stress from chronic and unpredictable maternal separation from the first to the fourteenth postnatal day in mice. The results observed included comparable changes in DNA methylation of stress-response genes such as CB1 and CRF2 in the cortex, as well as epigenetic alterations in transcriptional regulation gene MeCP2 in the brain of the offspring. As a result, the offspring were also more sensitive to stress, and these changes were persistent for up to three generations after the inflicted trauma. Another study from the journal of Translational Psychiatry states that “paternal preconception stress, regardless of whether the stress was experienced during early-life or adulthood, results in offspring with altered anxiety and depression-related behaviors, attributed to hypothalamic–pituitary–adrenal axis dysregulation.” These findings, apart from being fascinating and revolutionary in the realm of biological psychiatry, also shed light on the hold we can have over our offspring’s fate at a biological level. This also means that, because of this plasticity, we also have the potential to better our children’s future, make them stronger healthwise, and to a certain extent decrease their risk to develop health issues throughout the course of their lives. In this context, a 2017 study measured the epigenetic changes caused by healthy physical exercise in male mice’s male offspring by using a model of voluntary wheel-running. The results are far from uninteresting. The male offspring of male mice runners had suppressed reinstatement of juvenile fear memory, and reduced anxiety during adulthood. An odd detail however, is that no changes in these affective behaviors were observed in the female offspring of the male mice runners. These behavioral changes are said to likely be due to expressions of small non-coding RNAs that were altered in sperm cells of the fathers. Other studies went further and explored the potential for reversing the consequences of paternal early-life stress in offspring. A 2016 study published in the journal of Neuropsychopharmacology, “Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma” in fact states that the transmission of behavioral symptoms across generations can successfully be prevented by paternal environmental enrichment, and is an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. This discovery gives prominence to the influence of both beneficial and adverse environmental factors on transgenerational behaviors and put an emphasis on the plasticity of the epigenome across life.
This is however not all when it comes to epigenetics. Indeed, epigenome plasticity can be observed in a myriad of past historical events. We quickly approached how severe famine could influence gene expression in survivors as well as in their offspring. This as a matter of fact occurred during the 1958–1961 Great Chinese Famine, but also Ireland’s Great Famine of 1845–1852, or even the Swedish Famine of 1867–1869. Another sinister context where significant epigenetic changes were observed is that of slavery in Western colonies. The dark and tragic context of Western colonial slavery indeed constitutes a prime study case around how an entire race can be subject to epigenetic changes. This is because of the nature of the trauma inflicted, but also because of the duration of it. From the start of colonialism to the abolition of slavery, four centuries passed, during which African people were subject to repetitive trauma. Those included prenatal maternal stress, postnatal maternal separation, lifelong psychological and physical stress and nutritional deprivation. This means that generation after generation, trauma was passed on from adult to offspring, and contributed to the development of further health problems. In addition, an important detail we ought not to ignore, is the selection process which happened during the slave-trade. By slave-traders selecting which individual was the strongest, which male would work best in the fields, which female had the most potential to bare the most children, what happened is a literal filtering of undesired features amongst an entire demographic. This can in fact be described as a form of eugenics. Placed in a contemporary context, this can be linked to the common myth around Black people being more athletic than other races. Although greatly debated (among others because of the race factor), the consequences of such a long-term filtering process, coupled with the daily exposure to hard work and extreme physical activity, are not dismissible. This point has, validly, been taken into account by African-American activists, anthropologists and philosophers in their wish to see, some day, Black Americans receive reparations. Indeed, while most pro-reparation activists tend to argue their case on the basis of economic factors (four centuries of stolen labor, lack of professional opportunities, or even the 1921 Tulsa massacre and subsequent destruction as what was known as the Black Wall Street, then-pinnacle of Black American economy) it turns that there may be way more to argue on than we initially could have thought. Unlike economy, which, like a house, can be reconstructed, health isn’t always as easy to fix. It is of course not impossible to alter the trajectory of genetic expression (quite the opposite, that’s in fact the whole point of this article), but while economy can sometimes be fixed as rapidly as within one or two generations, health impairments can take double that to be corrected. For instance, Type 2 diabetes remains a rampant health issue in the African-American community. The presence of similar comorbidities amongst Black demographics and descendants of enslaved populations also contributes to placing the latter at greater risk in the context of a pandemic. Although we remain responsible for the better health of our offspring, the transgenerational effects of nutritional deprivation inherited from slavery are something we have to live with in present times, as most of those genetic alterations tend to last up to several generations.
So what can we retain from all this? It is a lot to digest, but it’s also groundbreaking news in the field of modern biology, and great news for those of us who have inherited trauma and predispositions to health adversity. We’ve understood that there seems to be certain windows of time in which transgenerational epigenetic changes happen. For example, for females, a key period for those changes to occur is during pregnancy. Likewise, the pre-puberty period in males has been observed to be a significant window. This helps us understand how genetic material is passed onto subsequent generations, but there are also windows we can open ourselves. Exercising is a good candidate in this context. Phenotypic plasticity, in a way, places the ball in our court. We have the choice to either create better health outcomes for future generations, or worsen them even more. So I guess it’s really up to us to decide. What do we want for ourselves, and what do we want for our children?
Sources
https://www.nature.com/articles/npp201687
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534950/
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00652-6/fulltext
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0676-3
https://link.springer.com/article/10.1007/s40610-016-0030-x
https://link.springer.com/article/10.1007/s40615-020-00928-y
https://www.theguardian.com/science/2015/jul/19/epigenetics-dna–darwin-adam-rutherford
https://medlineplus.gov/genetics/understanding/traits/eyecolor/
https://pubmed.ncbi.nlm.nih.gov/28463242/
Aude Calloch 