Why is it that one of the identical twins can have heart disease at the age of 50, while the other is running marathons in perfect health?
According to Dr. Carlos Guerrero Bosagna, it seems that this is due to the relationship between the innate and the acquired, or perhaps, to what we call epigenetics.
In this sense, according to Guerrero-Bosagna, epigenetics studies the interaction that occurs between genes and DNA, with the many small molecules inside the cells, which can activate or deactivate genes.
Think of our DNA as a recipe book where tiny molecules decide what goes into a recipe and how it is prepared. It is not the molecules themselves that make the decisions, but rather their presence and concentration that makes the difference.
This would mean that, although we are born with a certain genetic information, the habits (hopefully healthy and long-lasting) that we acquire in our lives can turn us into the best version of ourselves.
How Does Epigenetics Work in the Body?
Genes and DNA are expressed when they identify themselves and are transcribed into RNA by structures called ribosomes and translated into proteins. So, it is proteins that largely determine the characteristics and function of a cell.
Epigenetic changes can enhance or interfere with the transcription of specific genes.
The interference is identified in DNA or neighbouring proteins as being labelled with small chemical markers. The series of chemical tags that bind to the genome of a cell X is called the epigenome.
Some of these tags, such as those called methyl groups, inhibit gene expression by derailing the cellular transcription mechanism or causing the DNA strand to coil tighter around the gene, making it inaccessible. The gene is still there but switched off.
In the case of transcriptional enhancement, some chemical tags can reveal DNA, making it easier to transcribe, which stimulates the production of the protein that is affected.
Epigenetic changes can survive cell division, which means that they can affect an organism for its entire life and can be good, or bad in other cases.
When do epigenetics start to work in humans?
Cells in an embryo start with a master genome and as they divide, some genes are activated while others are inhibited. Over time and through epigenetic reprogramming, some cells become heart cells, while others become liver cells, for example.
Each cell type, of the approximately 200 cells in the human body, is based on the same genome, but has a particular epigenome.
Epigenome: The set of elements that regulate the genes of an organism and act on the genome.
The epigenome is also part of a dialogue between genes and environment. The chemical labels that activate or inhibit genes can be influenced by factors such as diet, exposure to chemicals and drugs that over time can result in disease.
Environmentally induced epigenetic changes are, in part, the reason why genetically identical twins can grow up to live very different lives from each other. As twins grow older, their epigenomes diverge, which can affect the way they age and their vulnerability to disease. It should be known that even social experiences can cause epigenetic changes.
In a study where rat mothers were not attentive enough to their offspring, the bubs' genes that help them cope with stress were methylated and inhibited. It seems that it doesn't end in that generation but may be inherited. Most epigenetic tags are erased when eggs and sperm are formed. But science is now detecting that some of these traces remain, passing these epigenetic traits on to the next generation. (1)
How to Juggle with Epigenetics
Your parent's experiences as a child, or decisions made as an adult, could possibly shape your epigenome as their son or daughter. Although the changes stick, they are not necessarily permanent. A balanced lifestyle, eating a healthy diet, exercising, and avoiding pollutants, for example, may, in the long run, support a healthy epigenome.
For now, science is just beginning to understand how epigenetics can, through a DNA sample, identify the chronological age of the subject under study and the implications for human development such as ageing, mental illness, heart disease and cancer.
Once we understand how the epigenome influences our organism, we may be able to influence it.
Epigenetic Mechanisms
To date, three mechanisms have been discovered that control gene expression at the molecular level. The first, as we saw above, is called methylation and is like chemical labels that are attached to genes to activate or inhibit them.
The second mechanism is the chemical modification of chromatin histones, such as acetylation. Like the recipe book above, this mechanism can change the density and allow access to genes for activation.
The third mechanism is microRNAs that are important for regulation when genes are activated or inhibited.
Dr Steve Horvath's Anti-ageing Epigenetic Clock
What Dr Horvath has done is a biochemical test that can be used to measure age using DNA methylation levels that tend to be very stable.
Biological ageing clocks and bio-indicators of ageing will find many uses in biological research, as age is a fundamental characteristic of most organisms.
By comparing DNA methylation age (estimated age) with chronological age, measures of age acceleration can be defined. A positive/negative value of epigenetic age acceleration suggests that the underlying tissue is ageing faster/slower than expected.
Thus, Dr. Horvath's approach is focused on,
The rate of epigenetic ageing of individuals and prediction of life span,
Cancer tissue,
Neuropathologies related to Alzheimer's disease,
HIV infection,
Parkinson's disease,
Developmental disorder: syndrome X, Epigenetic ageing, and cellular senescence.
Studies target more specifically:
Lifestyle. Although the factors are not very robust in terms of age acceleration in blood samples, results have shown that there is benefit from educational level, mainly plant-based diet, physical activity, moderate alcohol consumption and risks associated with metabolic syndrome.
Obesity and metabolic syndrome. A large study found that several biomarkers of metabolic syndrome (glucose, insulin and triglyceride levels, C-reactive protein, waist-to-hip ratio) were associated with accelerated epigenetic ageing in the blood. Conversely, higher levels of good HDL cholesterol were associated with a lower rate of epigenetic blood ageing. Other research suggests very strong associations between higher body mass index, waist-to-hip ratio and waist circumference and acceleration of epigenetic clocks, with evidence that physical activity may attenuate these effects.
Breast tissue and cancer. Since normal tissue that is adjacent to other types of cancer does not show a similar age-accelerating effect, this finding suggests that normal female breast tissue ages faster than other parts of the body. In addition, a three-clock epigenetic study has found that mDNA age was accelerated in blood samples from women without cancer, years before diagnosis.
Slow ageing of the cerebellum. An application of the epigenetic clock to 30 anatomical sites in six centenarians and younger subjects revealed that the cerebellum ages slowly: it is about 15 years younger than expected in a centenarian. This finding may explain why the cerebellum shows fewer neuropathological features of age-related dementias compared to other brain regions. In younger subjects (e.g., under the age of 70), brain regions and cells appear to be about the same age.
Heirs of centenarians age more slowly. The offspring of semi-supercentenarians (subjects who reached an age of 105-109 years) have a lower epigenetic age than age-matched controls (age difference = 5.1 years in blood) and centenarians are younger (8.6 years) than expected based on their chronological age.
Menopause accelerates epigenetic ageing. The following results strongly suggest that the loss of female hormones resulting from menopause accelerates the rate of epigenetic ageing of blood and possibly other tissues.
First, early menopause has been found to be associated with a greater acceleration of blood epigenetic ageing. Second, surgical menopause (due to bilateral oophorectomy) is associated with accelerated blood and saliva epigenetic age. Third, menopausal hormone therapy, which mitigates hormone loss, is associated with a negative acceleration of oral (but not blood) cell age. Fourth, genetic markers that are associated with early menopause are also associated with greater epigenetic acceleration of blood age.
Effects of sex and race/ethnicity. Men age faster than women according to epigenetic age acceleration in blood, brain, and saliva, but it depends on the investigated structure and lifestyle. The epigenetic clock method applies to all racial/ethnic groups examined in the sense that mDNA age is highly correlated with chronological age. But ethnicity can be associated with acceleration of epigenetic age. For example, Hispanic and Tsimané blood ages more slowly than that of other populations, which may explain the Hispanic mortality paradox.
Rejuvenating effect of blood stem cell transplantation. Haematopoietic stem cell transplantation, which transplants these cells from a young donor into an older recipient, rejuvenates the epigenetic age of the blood to that of the donor. However, graft-versus-host disease is associated with an increase in DNA methylation age.
The epigenetic clock can currently give us guidelines on our biological age compared to our chronological age and interventions in the above fields are planned, however, while we get there, our mums were right: eating healthy, getting enough sleep, being active both physically and mentally and controlling alcohol consumption, lay a very good epigenetic foundation.
References:
Information based on interview with Dr. Rhonda Patrick and Dr. Steve Horvath. https://podcastnotes.org/found-my-fitness/dr-steve-horvath-on-epigenetic-aging-to-predict-healthspan-the-dna-phenoage-and-grimage-clocks-found-my-fitness-with-dr-rhonda-patrick/