How to activate your anti-aging epigenetic clock

Why can one identical twin have heart disease at age 50, while the other is running marathons in perfect health?

According to Dr. Carlos Guerrero Bosagna, this seems to be 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 is responsible for studying the interaction that occurs between genes and DNA, with the many tiny molecules inside cells, which can activate or deactivate genes.

Let's think of our DNA as a recipe book where tiny molecules decide what goes into a recipe and how it is prepared.  The molecules themselves are not the ones that make the decisions, but rather their presence and concentration is what makes the difference.

This would mean that, although we are born with certain genetic information, the habits (hopefully healthy and long-lasting) that we acquire in our life can turn us into the best version of ourselves.

 

How does applied epigenetics work in the body?

Genes and DNA are expressed when they identify each other 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.

Interference is identified in neighboring DNA or proteins as they are tagged with small chemical markers.  The series of chemical labels that are attached to the genome of a cell X is called the epigenome.

Some of these tags, such as so-called methyl groups, inhibit gene expression by derailing the cell's transcription machinery or by causing the DNA strand to wrap more tightly around the gene, making it inaccessible. The gene is still there, but turned off.

In the case of enhancing transcription, some chemical tags can reveal DNA making it easier to transcribe, which stimulates the production of the affected protein.

Epigenetic changes can survive cell division, meaning they can affect an organism for its entire life and can be good, or bad in other cases.

 

When does epigenetics start to work in humans?

The cells of an embryo start with a master genome and as they divide, some genes are turned on while others are turned off.  Over time and through epigenetic reprogramming, some cells become heart cells, while others become liver cells, for example.

Each type of cell, of the approximately 200 that the human body has, has the same genome as its base, but a particular epigenome. 

Epigenome : 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 the environment.  Chemical tags that activate or inhibit genes can be influenced by factors such as diet, exposure to chemicals and medications that over time can result in disease.

Environmentally induced epigenetic changes are partly the reason why genetically identical twins can grow up to have very different lives from each other.  As twins grow older, their epigenomes diverge, potentially affecting how they age and their vulnerability to disease.  It should be known that even social experiences can cause epigenetic changes.

In a study where mother rats were not attentive enough to their offspring, the babies' genes that help them cope with stress became methylated and inhibited. It appears that this does not end with that generation, but may be hereditary. Most epigenetic tags are erased when eggs and sperm are formed. But now science is detecting that some of these imprints persist, passing these epigenetic traits on to the next generation. ( 1 )

 

How to juggle with epigenetics

Your mother or father's experiences as a child, or decisions made as an adult, could possibly shape your epigenome as their son or daughter.  Although changes stick, they are not necessarily permanent.  A balanced lifestyle, such as eating a healthy diet, exercising and avoiding pollutants, could, in the long run, contribute to 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 their human development such as aging, mental illness, heart disease and cancer.

Once we understand well how the epigenome influences our organism, we might 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 the chemical labels that are placed on genes to activate or inhibit them .

The second mechanism is the chemical modification of chromatin histones, such as acetylation. Like the recipe we saw 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-aging epigenetic clock

What Dr. Horvath has done is a biochemical test that can be used to measure age using DNA methylation levels, which tend to be very stable.

Biological aging clocks and bio-indicators of aging will find many uses in biological research, since age is a fundamental characteristic of most organisms.

By comparing DNA methylation age (estimated age) to chronological age, measures of age acceleration can be defined. A positive/negative value of epigenetic age acceleration suggests that the underlying tissue is aging faster/slower than expected.

Thus, Dr. Horvath's proposal focuses on

The speed of epigenetic aging of people and prediction of life span,

Cancerous tissue,

Neuropathologies related to Alzheimer's disease,

HIV infection,

Parkinson's disease,

Developmental disorder: syndrome X, epigenetic aging and cellular senescence .

 

The studies focus more specifically on:

Your lifestyle.  Although the factors are not very solid regarding the acceleration of age in blood samples, the results have shown that there is a benefit thanks to the educational level, a 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 aging in the blood. In contrast, elevated levels of the good HDL cholesterol were associated with a slower rate of epigenetic aging in the blood. Other research suggests very strong associations between higher body mass index, waist-to-hip ratio, and waist circumference and accelerated epigenetic clocks, with evidence that physical activity may attenuate these effects.

 

Breast tissue and cancer. Since normal tissue adjacent to other cancers does not show a similar age-accelerating effect, this finding suggests that normal female breast tissue ages faster than other parts of the body. Furthermore, a three-clock epigenetic study found that DNAm age was accelerated in blood samples from women without cancer years before diagnosis.

 

The slow aging 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 could explain why the cerebellum exhibits fewer neuropathological features of age-related dementias compared with other brain regions. In younger subjects (e.g., under 70 years of age), brain regions and cells appear to be approximately the same age.

 

That 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 aging . The following results strongly suggest that the loss of female hormones resulting from menopause accelerates the rate of epigenetic aging in blood and possibly other tissues.

First, early menopause has been found to be associated with a greater acceleration of epigenetic age in blood. Second, surgical menopause (due to bilateral oophorectomy) is associated with an acceleration of epigenetic age in blood and saliva. Third, menopausal hormone therapy, which mitigates hormone loss, is associated with a negative acceleration of buccal (but not blood) cell age. Fourth, genetic markers that are associated with early menopause are also associated with a greater epigenetic acceleration of age in blood.

 

Sex and race/ethnicity effects . Men age faster than women based on epigenetic age acceleration in blood, brain, and saliva, but it depends on the structure investigated and on lifestyle. The epigenetic clock method applies to all racial/ethnic groups examined in that DNAm age is highly correlated with chronological age. But ethnicity may be associated with epigenetic age acceleration. For example, the blood of Hispanics and Tsimané ages more slowly than that of other populations, which could explain the Hispanic mortality paradox.

 

Rejuvenating effect of blood stem cell transplantation . Hematopoietic stem cell transplantation, which transplants these cells from a young donor to 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 now give us guidelines about our biological age compared to our chronological age and interventions are planned in the above-mentioned fields, however, until we get there, our mothers were right: eating healthily, sleeping enough hours, being active both physically and mentally and controlling alcohol consumption, are very important.  good epigenetic foundations.

References:

Information based on interview with Dr. Rhonda Patrick and Dr. Steve Horvath.