DNA methylation: the key to predicting mortality

Since the beginning of time, humankind has searched for the secret to a long life.

Though ageing is typically defined by birth date, i.e. chronological age, what is becoming increasingly obvious is that while some individuals have accelerated ageing, and therefore risk of premature mortality, others can enjoy middle to old age with a physiology that appears decades younger.

Recognising that one of the great motivators in life is fear of loss, namely of health or life – what if there was a test to tell us if we had accelerated aging based on our current lifestyle habits, which could be reversible? It seems they are just around the corner.

One such test is DNA methylation, a well-researched tool that calculates biological age and subsequent risk of mortality, promising a glimpse into your health future.

WHY DNA METHYLATION IS THE KEY TO MORTALITY RISK ASSESSMENT

While DNA is fixed, the expression of DNA is not. Variable expression of DNA (known as epigenetic patterns) change based on what you eat, what toxic substances you may be exposed to, how much you sleep or exercise, ultimately influencing your risk of developing chronic conditions.

Epigenetics can be influenced by DNA methylation – when a chemical group (in this case methyl) is added to or subtracted from DNA. In most cases, methylation will turn genes “off”, while demethylation or hypomethylation switches genes “on”. Typically, ageing is accompanied by a general whole body “hypomethylation”.

In the last 10-15 years, research has examined how the methylation of DNA can affect biological age, creating an epigenetic clock.

For example, Hannum et al. (2013) and Steve Horvath (2013) were independently able to accurately determine the chronological age of anonymous individuals through DNA methylation screening, examining de-identified body tissue samples.

More importantly, there is an emerging and reproducible link between accelerated aging and early mortality. Identical twin studies have shown that the twin with unhealthy lifestyle choices will have lower methylation status of their DNA as they grow older – they die younger from age related diseases.

Marioni et al. (2015) found that if the difference between biological/epigenetic and chronological age was greater than five years, it was associated with a 21% higher mortality risk.

In addition to establishing biological age, research has also found that DNA methylation is associated with specific age-related diseases/conditions such as various cancers, Alzheimer’s disease, poor cognitive and physical functioning, and a variety of other age-related illnesses.

Studies show that non-genetic pathways, including lifestyle choices such as lower fish intake, moderate to high alcohol consumption, higher BMI, low physical activity levels, and low fruit and vegetable consumption, can influence biological age and risk of age-related conditions by up to 80%. These factors are linked with accelerated (epigenetic) ageing, i.e., one’s DNA methylation-predicted age is greater than one’s chronological age.

SO, WHAT DOES THIS ALL MEAN FOR HEALTHCARE PROFESSIONALS AND PATIENTS?

If someone is identified with poor lifestyle choices and thus accelerated ageing, the obvious question is – can anything be done?

The short answer is yes.

In theory, the individual should feel impelled to make lifestyle adjustments to slow the ageing process.

The trick, however, of promoting healthy ageing through DNA methylation technology, is actually motivating people to alter their behaviour.

In recent years, research has examined the reversibility of biological age, which is significant in the world of illness prevention.

Fitzgerald et al. (2021) showed that DNA methylation age can be reduced by focusing on diet, sleep, exercise, relaxation, and supplements. Other studies suggest the same potential reversibility.

Even for medical professionals, knowing whether one’s health is on track could be a great intervention if it spurs change or reinforces positive lifestyle habits.

LOOKING TO THE FUTURE

As the world of epigenetics evolves, we can look forward to improved medical and healthcare practices that may further our understanding on the treatment of many illnesses, leading to better prevention strategies and potentially decelerating the ageing process.

It is feasible that as part of a preventive health check, a patient could have their epigenetic age measured with a saliva sample or blood test. The results can then be provided as part of their panel of regular testing, for example, in addition to cholesterol, blood sugar level etc, and ultimately be tracked over time.

These test kits have the potential to become much more mainstream and locally available as a growing number of people seek to alter their genetic “fate”.

All in all, DNA methylation as a tool enables individuals to assess their mortality and optimise their health outcomes by making more informed decisions. It paves the way for health professionals to give truly customised advice and recommendations, thereby empowering individuals to take charge of their own wellbeing.

As a physician, I am hopeful that further research in the epigenetics space will offer new possibilities in healthcare and open new doors in the fight to increase longevity.

Dr John Cummins is the chief medical officer at insurance provider PPS Mutual and CEO and medical director of Executive Medicine.