There is a long-standing debate regarding human health and development — nature vs nurture. The science of epigenetics crosses this divide, bridging these polarities into a holistic framework, giving us greater insights and inspiration to support our health within our environment.
Our genetic background is determined by our ancestors. We are the sum total of our hereditary DNA plus the environmental impacts on the genes of our ancestors, which were then transmitted to their off spring. We inherit more than our genes — research shows that we also inherit the biological consequences of epigenetic modifications in our ancestors.
The genetic background a person inherits determines a “susceptibility” to health or disease — with varying degrees of potential severity. Whether genes are switched on and off , and therefore manifest as health or disease, is determined by the person’s environment and choices — including diet and lifestyle choices, stress levels, spiritual beliefs, psychology, environmental toxins, pharmaceuticals; all our experiences — mind, body and spirit can impact on our genes. New data also links learning, intelligence and the development of human consciousness as other powerful factors shaping our genes.
The genome is a historical record of specieswide environmental adaptations, and as such facilitates evolution of the species, whereas epigenetic memories are a historical record of individual gene-environment interactions passed onto the children.
Your DNA (and your genes) are not your destiny — you can alter inherited tendencies to disease/health.
The history and definition of epigenetics
Conceptually, “epigenetics” can be traced back to the Greek philosopher Aristotle in 350BC when he proposed that humans develop from unformed matter into an organic whole by a “vital cause”. But it was Dr C Waddington (1905–1975), with his interest in the development from the embryo to its whole organism, who is generally accepted as the father of epigenetics.
The term epigenesis has been used since the 17th century, literally meaning of “above” or “on top of” genetics. In scientific research, it first appeared in the 1930s. It was only in 1969 that Griffith and Maler first suggested that epigenetic modification could alter gene expression, and its contemporary meaning emerged from this in the 1990s.
Research defines epigenetics as “the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself”. It is inheritable but can be reversed and while it doesn’t alter DNA sequences, it can modify how the body interprets a DNA sequence, and these changes can persist through cell division.
Epigenetics refers to processes that regulate the level of gene activity, being able to turn genes “on” or “off ”. These are not encoded in the DNA sequence but rather they affect how cells “read” genes — we inherit an unknown quantity of additional information that is not encoded in our genes. However epigenetic inheritance, just like genetic inheritance, can be transmitted to our descendants.
Genotype and phenotype
Genotype refers to the genetic makeup of an individual, the specific combination of genes they inherit from their parents — that determines various characteristics by triggering chemical modification in the DNA. Conversely phenotype is the observable physical, physiological, and behavioural traits that result from the interaction between an individual’s genes and their environment — what you can see and measure, such as hair colour, height, and the presence of certain diseases. Genotype is the genetic code, while phenotype is how those genes manifest in the individual. Epigenetic factors change the phenotype, without changing the genotype, which in turn determines how genes are expressed.
It is therefore important to understand how epigenetics works to know how we can live healthy and productive lives.
Pathways – a bit of biochemistry
The genetic material of an organism is located in the DNA (deoxyribonucleic acid). A single, lengthy strand of the DNA molecule has numerous genes, regulatory regions, and other nucleotide sequences as part of its structure — an organism’s genetic code is defined by the precise configuration of these. DNA strands are tightly coiled and packaged around proteins called histones which arrange and compress the DNA into a form that can fit inside the cell nucleus (preventing them from becoming tangled and damaged) — called the chromatins. The chromatins compact further to form chromosomes. Chromosomes are copied and passed on to daughter cells during cell division, guaranteeing that every new cell has the correct genetic makeup. Accurate regulation of gene expression and the preservation of genetic stability depends on the correct arrangement and packaging of DNA in the chromosomes.
There are various processes involved in this: DNA methylation is the process that involves adding a chemical (methyl) group to a specific place on the DNA, blocking proteins that “read” the gene. Methylation turns genes “off ”, while demethylation turns genes “on”. Methylation has a significant role to play in most chronic illnesses including psychiatric disorders (it also regulates neurotransmitter function). Important nutrients that regulate methylation are vitamins folate, B6 and B12.
- When the histones are tightly packed, the proteins that “read” the gene have difficulty accessing the DNA, and the gene is therefore turned “off ”. If loosely packed more DNA is exposed so the proteins can reach the gene and turn it “on”. The histone code is a secondary hereditary code formed on top of the genetic backbone and controls the way the genetic information is expressed. Chemical groups can be removed or added to histones to regulate gene expression. Histone proteins and histone deacetylases (HDAs and HDAC enzymes) are influenced by a range of dietary components.
- A third process involves non-coding RNA. DNA provides instructions for making coding and non-coding RNA. Coding RNA produces specific proteins, non-coding RNA helps control gene expression, modify histones and influence gene activation. Non-coding RNA plays a major role in biological processes and can be a causal factor in human pathology, with studies researching the relationship between these, exercise and nutrition.
- The role of telomeres and telomerase. Telomeres are the protective end caps on chromosomes, and the enzyme telomerase helps to rebuild telomeres. The length of the telomeres influences whether target genes are switched on or off and telomerase activity is closely linked to both psychological stress and physical health.
Epigenetics – a lifelong role in the body
Epigenetic changes start in the embryo where they determine whether a cell becomes a muscle cell or a nerve cell (for example), by activating the genes essential for the function of that cell and suppressing genes relevant to different cellular functions. A vast array of successive epigenetic modifications ensures the creation of a healthy individual.
As we develop, two factors have a powerful influence on epigenetic mechanisms — our lifestyle choices and our environment. Lifestyle choices include foods we eat, behavioural habits, stress (physical or psychological), meditation and spiritual practices, level of physical activity, work habits (especially night shifts), smoking, alcohol and drug consumption, medications (pharmaceutical and natural) etc. Environmental factors which include any pollutants (heavy metals, chemicals), air pollution, water pollution, plastics, pesticide and herbicide residues on foods etc, all impact on which genes are activated or not.
Factors influencing our genes
Stress
Stress (in its multiple forms) impacts significantly on epigenetic mechanisms, particularly DNA methylation and telomere stability. Events throughout our whole lives, from infancy on, impact on gene expression and therefore the state of our health and longevity.
Meditation, spiritual practices and epigenetics
Research is proving the epigenetic benefits of meditation, including inflammation reduction and protection of the telomeres. Distressed breast cancer survivors who practiced meditation could maintain their telomere length, compared to those not meditating — who saw their telomeres decrease in length. Shortened telomeres relate to the development and progression of a variety of cancers. These are also shorter in those diagnosed with diabetes, heart disease and high stress levels.
Overall, individuals who engaged in spiritual practices such as meditation, yoga and Tai-chi showed improved DNA methylation and increased remission of malignant cancers.
Spiritual practices
An interesting study investigated the impact of a range of stressors including early life stress, low socio-economic status, work stress, social adversity, bereavement, loneliness and social isolation on our health — seen through the lens of epigenetics and gene expression — and how spiritual support networks moderate these stressors.
The research investigated Christian, Muslim and Hindu religious practices and showed that individuals with regular spiritual practices have strong relationships — family and community, religious affiliation, prayers and divine interaction — and these correlated with increased health and longevity — in part by increased happiness and more avoidance of risky behaviours.
Spiritual networks are organisations based on hope, faith and divine providence, the research showing that these enhance human gene expression, health status, prognosis and survival through various epigenetic pathways including DNA methylation. Spirituality plays an important role in positive epigenetic regulation.
Ageing
Our lifespan is largely determined by epigenetics (rather than by genetics), influenced substantially by dietary and environmental influences. Epigenetic information can also function in a transgenerational manner and influence the lifespan of our children.
Age-related diseases such as type 2 diabetes, cardiovascular disease, and cancer involve epigenetic modifications, where accumulation of minute changes in the epigenome over time manifests as disease.
The impact on specific systems
Cardiovascular
Epigenetic modification plays an important role in the development and degree of cardiovascular disease — it is considered the major cellular response regulation mechanism to environmental changes.
Metabolic syndrome and cancer
Metabolic syndrome is an increasing problem today and includes diabetes, cardiovascular disease and cancer, as well as increased morbidity and mortality.
Overeating or high-fat diets lead to significant changes in gene expression — partly as an adaptive mechanism to the excess calories, and can lead to the activation of various cancers. High-sugar diets have similar effects.
These changes can start in the womb. Studies of maternal nutrition on the susceptibility of the off spring to metabolic diseases, indicate that pregnant women consuming a high-fat diet induce epigenetic changes, predisposing their off spring to metabolic syndrome later in life. While there have been multiple rodent studies, human studies showed similar changes. Rat studies also indicated intergenerational transmission of metabolic syndrome with the second generation showing insulin resistance — even when fed a normal diet.
Similar outcomes occurred when pregnant mice were fed a high glycaemic diet resulting in a rapid rise in blood glucose — their off spring had increased birth weights and impaired glucose tolerance.
Butyrate-fed mice showed better oral glucose tolerance and lower fasting glucose and insulin levels. Butyrate (produced in the gut from dietary fi bre) can be protective of high-fat-induced glucose intolerance and insulin insensitivity and reduces the risk of colon cancer through the HDAC epigenetic mechanisms.
Healthier diets in adults, supplemented with sulforaphane, curcumin, green tea, quercetin and butyrate have been shown to protect against metabolic syndrome by improving gene expression.
Cancer
According to research, cancer is both a genetic and an epigenetic disease. The major hallmarks of cancer involve a significant disruption of DNA methylation, histone modification and chromatin.
Research has shown that specific chemopreventive agents that target the epigenome include food-based compounds — polyphenols, genistein and isoflavones (fermented soy), curcumin, resveratrol, lycopenes and butyrate; isothiocyanates and diallydisulfi des from the allium species (garlic, onions); and sulforaphane and indoles from cruciferous vegetables.
Research on mice fed a fruit, seed and peel diet, high in flavonoids and polyphenols for 28 days, showed the resveratrol component of this diet inhibited specific genes, delaying cancer development and tumour progression.
Sulforaphane in broccoli, brussels sprouts, cabbage and kale induces phase II liver detoxification enzymes and is an antioxidant. Sulforaphane also inhibits HDAC activity and induces NRF2 activity, reducing cancers such as colon and kidney, through these epigenetic mechanisms.
Curcumin reduces the risk of various cancers and is beneficial for the prevention of high-fat-induced metabolic syndrome, and consumed with green tea (polyphenols), works as an anti-inflammatory through histone epigenetic mechanisms.
Neurological
Epigenetic regulation of neuronal plasticity is an important mechanism whereby foods and herbs can impact positively on brain function and cognition. There is a strong relationship with foods on energy metabolism and synaptic plasticity in the brain.
Foods that improve brain function (working synergistically with exercise) are the omega-3 fatty acids (especially DHA). Rat studies with diets enhanced with DHA showed significantly increased spatial learning ability. The DHA diet increased levels of brain-derived neurotrophic factor (BDNF) and exercise enhanced this effect. Curcumin is synergistic with DHA.
BDNF is crucial for synaptic plasticity, learning and memory, promotes mental health and reduces the risk of neurological disorders.
Fertility
Nutrition and lifestyle have a significant impact over epigenetic mechanisms, thereby making these a major factor in the pathogenesis of many diseases including infertility. Epigenetic mechanisms of individuals with infertility are different from healthy (and fertile) individuals.
Research on male infertility has found that epigenetic modifications (mutations and polymorphisms in genes reduce sperm production and viability) are possibly one of the main factors in the cause of unexplained male infertility. Infertility in the male contributes to about 50 per cent of the cases of infertility in couples.
Pharmaceuticals and Pharmacogenetics
Given the decades that it takes to accumulate epigenetic changes resulting in disease, while pharmaceuticals may relieve symptoms of pathologies temporarily, it is unlikely that they could undo epigenetic changes without side effects.
It is becoming recognised that pharmaceutical drugs can also cause persistent epigenetic changes and are potentially responsible for iatrogenic disease — the side effects of which can include heart disease, cancer, neurological and cognitive disorders, fertility problems etc, through a variety of epigenetic mechanisms. Employing a systems biology and epigenetic approach into the safety assessments of all pharmaceutical drugs is a whole new field of research — pharmacogenetics.
From a Dietary Perspective
Everything we consume impacts on our health. The digestive system receives the greatest environmental challenge of all as we are constantly eating foods that are “non-self” — and if functioning correctly, the gut has multiple powerful systems to deal with these challenges. DNA methylation is difficult to reverse with diet alone; changing the epigenome by regulating histone enzymes with dietary changes is more effective. While almost everything we come into contact with impacts on our genes, research has shown that some components in foods are more powerful regulators of our health than others. Dietary components such as resveratrol, EGCG (green tea), genistein (fermented soy), indoles and sulforaphane (cabbage, broccoli), and curcumin (turmeric) significantly improve histone enzyme modifications. Nutrients are important for disease prevention, research showing that nutrients targeting the epigenome include folate, quercetin, retinoic acid and selenium.
Strategies for a healthier life
Every choice we make in our daily lives (including what appear to be minor choices such as what to wear, what to eat, how we manage stress and conflict) impact on our genes. Our emotional states are controlled by hormones, and genes synthesise hormones — so even management of emotional responses, and our ability to express ourselves in our daily lives depends on our genes and how they function.
Biological measures already show us that stress isn’t all in the mind but has powerful eff ects physiologically. Psychology and biology are intimately connected. Even our brains are shaped by our thoughts.
Testing
As genetic testing falls in price and complexity, individualised treatment plans based on genetic testing may become the way of our future. For example, we will be able to measure whether an individual responds most effectively to a mixture of Tai-chi and fish oil, or methylation factors and yoga. These tests will not involve a blood test but instead a simple salivary swab will show results in seconds. Highly personalised medicine that measures biological markers showing the effectiveness of spiritual beliefs in a person will be implemented, along with physical and metabolic measures and energy medicines.
Summary
The research on epigenetics is exciting — it informs the basic principles that have always governed the health of humans — recognising and (where possible) avoiding negative environmental influences — chemicals, electromagnetic fields, heavy metals, plastics etc. Investigate herbal and nutritional foods to support your health and use these (when applicable) instead of pharmaceuticals, and if pharmaceuticals are essential, learn how to reduce their side effects using plants and foods. Knowledge is vital, as is learning how to detoxify/neutralise these challenges to your health.
Food choices are critical, and with food now a big environmental challenge, choosing organic, unprocessed fresh foods (that support your blood type) is becoming increasingly important. Eating a diet with adequate proteins (including unfarmed, small, deep-sea fi sh for thyroid support), growing and preparing your own food as much as possible (or knowing the farmers who do grow your food), avoiding food you are allergic to or intolerant of, and consuming a wide variety of food as close to the natural farm product as possible are all essential for health.
Avoid processed sugars and salt and excess fried or fatty foods.
Ensure you consume sufficient essential fatty acids (particularly omega 3). Regularly consume fermented probiotic foods and high soluble fibre prebiotic foods to support good gut function and a healthy microbiome.
