Biological Age And Epigenetic Clocks: Are We Getting Closer To Cheating Death?

Humans are living longer and healthy lives now more than ever and companies in Silicon Valley are investing billions into finding ways to avoid and even reverse the ageing process. Pharmaceutical and biotechnology companies around the world have shifted their work and research from trying to prevent the threat of immediate death to extending life.

In 2014, Joon Yun, a hedge fund manager, set up a $1 million prize, challenging scientists to “hack the code of life” and push the human lifespan past its apparent maximum of around 120 years. Living longer, healthier lives is something a lot of people are interested in.

And one part of this quest could lie within the field of epigenetics. But what exactly is epigenetics? What is a biological clock? And how do they relate?

What is Epigenetics?

Epigenetics refers to the study of changes to gene expression that occur within organisms but where there is no change to the DNA sequences.

Epigenetic changes, unlike genetic changes, are reversible and do not change the genetic code in cells. However, the epigenetic changes will still modify how a body interprets the DNA sequences and the reactions that ensue.

The epigenetic changes work by attaching modifications to the DNA – but, as mentioned above, without changing the DNA building blocks – thus turning specific genes on or off. Different chemical components will attach to or fall off DNA strands. This will in turn influence the production of proteins in cells. This mechanism, if working properly, ensures that the cell is only producing the necessary proteins it needs to function.

The complete set of DNA within a cell is called a genome, whilst all the modifications that influence the expression of the genes are called the epigenome. The epigenome can be influenced by a whole set of external factors such as activity levels, diet, stress, drinking, smoking, environment, and socio-economic status, the list is endless.

Furthermore, whilst some epigenetic changes will stay consistent throughout a person’s lifetime, others will change with age. Researchers are yet unclear as to why this happens.

DNA Methylation: The Key Behind Epigenetic Aging

DNA methylation is a common epigenetic mechanism which plays an important role in a range of cellular processes such as gene suppression, chromosome stability, embryonic development, genomic imprinting, and chromosome inactivation.

When the DNA methylation process stops working properly, this has been linked to negative health outcomes such as cancers, cardiovascular diseases, atherosclerosis, and nervous disorders.

Steve Horvath, a professor at the University of California, Los Angeles, found that the methylation process could be a good gauge of a person’s biological age. Horvath and his team gathered and analysed more than 13,000 human samples. They then developed an algorithm which could quite accurately determine a person’s biological age.

In 2013, Horvath developed his famous Horvath clock, which is one of the most used epigenetic clocks to this day. In essence, the idea behind this clock and other similar ones is that they’ll show how much organs have degraded. This in turn could help predict how many healthy years an individual still has, although there is still much debate about how accurate these clocks can be.

Horvath refers to his clock as a pan-tissue clock, as it’s capable of estimating the age of most organs in the human body. This clock was developed using methylation data from over 8,000 samples from more than 50 different cell types and tissues. He then used an algorithm to estimate the chronological age of an individual using a cell sample.

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Reversing signs of ageing

Steve Horvath was also involved in a small clinical study in California that, for the first time, seemed to reverse signs of ageing in humans.

Over a year, nine healthy males aged between 51 and 65 were administered a combination of three common drugs – one growth hormone and two diabetes drugs. By the end of the year, it came across that on average, the individuals had knocked 2.5 years off their biological age, as measured by Horvath using an epigenetic clock. There were also signs that the participants’ immune systems had rejuvenated.

This came as a huge surprise to the researchers, who were expecting the biological clock to slow down rather than reverse. Whilst this was a very small study, unblinded and with no placebo control arm, the results were still promising. Still, there is a long way to go before we are actually able to reverse the ageing process.

The researchers are now running a randomized and placebo-controlled phase II replication of the initial study on a larger group of 85 people.

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What do the findings on biological ageing mean for the future?

Many of the ageing clocks that have been developed up until now still present challenges. The main one is that they are ‘noisy’ meaning that sometimes, the small changes that occur through the methylation process over time can then be magnified by errors in methylation estimates. This then leads to results that are widely off the mark.

Whilst these clocks might be a relatively good indicator of an individual’s overall health, and many researchers are working to make these clocks more accurate, they are at present not accurate enough to count on.

This technology is still in its infancy but in the future, it presents much potential, especially when it comes to clinical health checks, where these epigenetic clocks could be used, alongside other tests such as cholesterol and blood pressure, to gain a better overall picture of a person’s health and how it might evolve.

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