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Does epigenetics hold the key to human longevity?

Does epigenetics hold the key to human longevity?

No one likes getting old. Of course, some of us grow old gracefully but for many it can mean developing illnesses like Dementia and Alzheimer’s, losing mobility and even our independence. However, through the exploration of epigenetics, researchers are finding that there could be a way to reverse our biological age - or at least promote long term health.

‘You’re only as old as you feel’, in some ways, this is true. We have two different ages; chronological and biological. Our chronological age refers to the number of years a person has been alive, while our biological age takes many lifestyle factors into consideration, comparing the age at which our body functions with average fitness and health levels. “We all age biologically at different rates according to our genes, our lifestyles, what we eat, how much we exercise and the environments we are exposed to,” says Dr. Tom Stubbs, CEO at Chronomics. “Our biological age is what ultimately determines our lifespan, not our chronological age.”

One useful tool, which can be used to measure biological age is the epigenetic clock, developed by Steve Horvath, in 2013, this is the most accurate quantifier of biological age. The epigenetic clock is a mathematical model, which predicts age by measuring DNA methylation levels in different sites across the genome (a set of genes or genetic material present in a cell). “Using the study of DNA methylation to identify biological age, we hope to identify ways to control gene expression, which could hold the key to human longevity,” adds Dr. Stubbs.

To help us better understand the epigenetic clock and the benefits of knowing our biological age, researchers have been carrying out a number of studies. Daniel Belsky and his team at Duke University, United States, studied 18 markers of cellular ageing – including blood pressure and cardiovascular function – in almost 1,000 adults. They found that some were ageing far faster or slower than their birth certificates would suggest, with some up to 10 years younger than their chronological age and others as much as 23 years older. Similarly, when James Timmons and colleagues at King’s College London examined expression of 150 genes associated with ageing, they found that biological age was more closely tied to risk of diseases such as Alzheimer’s and osteoporosis than chronological age.

While finding out we’re aging at a much faster rate than we should be and are at risk of developing serious illnesses, knowing our biological age almost gives us a second chance as we’re able to take steps to reverse our epigenetics, like lowering our risk of cardiovascular problems by adapting our diet and increasing our exercise. As Horvath says: “It sounds like science fiction, but conceptually it’s possible. All epigenetic marks are reversible, so in theory it’s possible to reset the clock.”

With our diet being a key trigger for epigenetic change, researchers have been reviewing whether how much we eat can affect DNA methylation, too. Using mice as the subject, researchers restricted the food intake of mice to 40% of their counterparts. They found that dietary restriction controlled genes involved in establishing one type of epigenetic change, which resulted in a 30% increase in lifespan. Oliver Hahn, PhD Student in the Partridge Group at the Max Planck Institute for the Biology of Ageing and lead author of the study said: "Dietary restriction partially protects against age-induced methylation changes whilst simultaneously instigating the reprogramming of lipid metabolism genes, which seems to result in beneficial changes to which help our bodies function better".

Epigenetic studies on mice continue to delve into the unimaginable, in the hope that the findings will be dramatic enough to prompt a similar study on humans - which would take a lot longer as we age a lot slower than mice. However, investigators at Harvard Medical School think they may have found the key to restoring youthful vitality, by reversing the aging of blood vessels, which has already prompted clinical trials on humans. Researchers found a way to reverse vascular aging (in mice) by boosting the presence of naturally occurring molecules in the body, which amplify the physiological response to exercise. In some cases, the mice showed between a 56% and 90% greater exercise capacity, compared with untreated mice.

So it’s true, one day we really may be able to live beyond our years, run marathons with lungs 10 years younger than we feel (though maybe not our knees), and in turn cheat the diseases that come with old age - it certainly is a very exciting time to be ‘alive’.

Katherine Brook

1. S. Horvath, 2013 ‘DNA methylation age of human tissues and cell types’.

2. Belsky DW*, Caspi A, Kraus W, Cohen HJ, Ramrakha S, Poulton R, Moffitt TE. Impact of early personal-history characteristics on the Pace of Aging: Implications for clinical trials of therapies to slow aging and extend healthspan. Aging Cell, published online April 12, 2017.

3. Timmons, King's College London: ‘A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.’ 2015.

4. Max Planck Institute for Biology of Ageing and the Cluster of Excellence for Aging Research CECAD, Germany, ‘Dieting causes changes during aging’, 2017.

5. Harvard Medical School: ‘Impairment or an Endothelial NAD+1H2S Signaling Network is a Reversible cause of Vascular Aging’: 2018.

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