Epigenetic Clocks Reveal We Might Be Getting Old Too Fast

Suppose that DNA is the great recipe book of our body and that our genes describe each of these recipes step by step. In this analogy, epigenetics would be the way our bodies add sticky notes to those recipes to change the way we execute a certain step or skip it.

In other words, epigenetics is an emerging field of science that studies hereditary changes caused by the activation and deactivation of genes that do not involve modifications in the DNA sequence.

Going back to the recipe book, the perfection of the result -be it a lemon cake or a Boeuf Bourguignon– It will not only depend on the quality of the ingredients or our culinary skills. It also influences what those sticky notes indicate.

Thanks to epigenetics, our body can change the genetic expression throughout life. It does this, among other mechanisms, by using tiny chemical markers that are added to or subtracted from the DNA sequence based on the environment, our experiences, and what we inherit from our parents.

One of the most important changes is called methylation, which adds a chemical group (methyl) to the DNA molecule. And it seems to be directly related to how and why we age. It turns out that with age, methylation declines across the board, increasing the risk of turning on genes that express impairment and disease. Therefore, knowing the amount and sites of DNA methylation could be a useful way to “measure” aging.

Epigenetic clocks to predict biological age

Epigenetic clocks are molecular analyzes that fairly accurately quantify aging. To do this, they use mathematical formulas that identify portions of the DNA called CpG islands. Specifically, these formulas detect which of these islands are methylated and which are not. When we accumulate many CpG islands that are not methylated, protective genes are inactivated while genes that harm health and shorten life expectancy are activated.

There are different types of watches. Some that better predict biological age in animals and others in humans. Some allow a greater repertoire of cells and tissues to extract DNA. Finally, there are epigenetic clocks that could predict the risk of dying or suffering from a neurodegenerative disease.

Such differences should not divert us from a fundamental question: epigenetic clocks can help us both to unravel the molecular mechanisms that speed up or slow down aging and to identify the factors that increase its speed. In this way, we can propose interventions that allow us to slow down and even reverse this process.

The epigenetic clock that best predicts age in humans was designed by Steve Horvath in 2013. Horvath was not interested in describing age-associated methylation patterns. Actually, he wanted to associate them with sexual preferences. But the ways of science are mysterious and he ended up creating the most accurate standard for measuring biological age. To design it, he analyzed 8,000 samples of 51 types of tissues and cells.

Some epigenetic clocks are available for commercial use. You only need to collect three drops of blood, send them to the laboratory and in five weeks you will know your biological age. Do not be surprised if this does not match the age indicated on your identity document. Epigenetic clocks have revealed that chronological age and biological age are not synonymous: the years since we are born can differ from our age determined by the degree of deterioration of our cells and organs.

Obesity speeds up the epigenetic clock

According to an old saying, “the excesses of our youth are bills of exchange issued against our age, which we pay back with interest 30 years later.” If biological age and chronological age mark different rhythms, it could be because the consequences of such excesses have appeared in advance. In fact, those who are overweight or obese cross the threshold for chronic disease much sooner than those of a healthy weight.

Although aging is a normal and natural process, the accumulation of degenerative damage does not occur only in people of advanced age. Obesity turns on the same biological signals that are attributed to the passage of time and could be a factor that accelerates aging.

Several studies that have used epigenetic clocks show that obesity changes gene expression in various organs, tissues, and cells, including the liver and leukocytes (or white blood cells). In fact, this occurs in people in their early 40s when they are obese.

Can we slow down the clock?

One of the great discoveries of epigenetic clocks has to do with the possibility of readjusting the epigenome. Unlike mutations, methylations are potentially reversible changes. This opens the door to interventions that allow regulating the rhythm of aging.

The control of food intake has shown positive effects on longevity and once again highlights the benefits of a diet low in calories, but sufficient in the supply of nutrients. Furthermore, caloric restriction is one of the most effective nutritional manipulations with effects on the epigenome, resulting in a longer and healthier life.

However, chronic caloric restriction is not easy to implement in humans, as it leads to a reduction in intake of between 10% and 40% while maintaining all nutritional requirements. As an alternative, some scientists propose intermittent fasting.

For the same reason, the largest body of evidence on the effects of this dietary format on epigenetic clocks comes from rodent models. These are well-known models of aging that may yield new insights into the relationships between epigenetic markers and interventions designed to increase healthy life expectancy that cannot be easily performed in humans. Six investigations have used epigenetic clock in rodents and in five the operated animals were younger with respect to their epigenetic age than the non-intervened animals.

The next challenge will be to transfer these findings to human beings of all ages and to identify time windows in the different interventions that are especially beneficial in extending healthy life expectancy.

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