The Promise of Immortality

Part 1: Turning back the epigenetic clock

This three-part series is dedicated to the latest progress in longevity research. Before we talk about how scientists plan to help us live longer, however, we have to talk about epigenetics. Strap in, and follow along!

My birthday was a couple of weeks ago, and it made me think about my mortality.

Not in a morbid way. On the contrary, the passing of time makes me want to celebrate life as much as I can, while I still can. I’m not one of those people who puts off the gratification of doing the things I love—like traveling the world—until retirement. By the time we get to retirement age, the world may look very different: the glaciers may no longer be there to see, certain countries may forever shut their borders to travelers, future pandemics may restrict our movements or the money we’ve saved up for retirement may evaporate in the rising heat of inflation.

Even if none of my pessimistic predictions come to fruition, we may simply be too tired, achy and cranky to enjoy hiking up to Machu Picchu or kayaking through the mangroves of the Yucatan. Time is ruthless when it comes to taxing our vitality: no matter how much we try to preserve our health and strength, the biological clock in our body keeps a molecular score of how much we have lived and how many years we still have left.

Aging may be inescapable but the fight against it is equally unyielding. Humanity has been chasing the dream of slowing down or even reversing aging for millennia, starting from the Ancient Greek myths and legends to the arduous labor of medieval alchemists and the exploits of Ponce de Leon who traveled to Florida in search of the fountain of youth long before it became Americans’ favorite retirement destination.

Today, when the mystics and explorers finally gave up on finding the secret of eternal youth, biotech is stepping up to the challenge of slowing down biological time. And it looks like we might finally be onto something.

(Epi)Genetic clocks

Thanks to the breakthrough discoveries of the past couple of decades, the paradigm of aging is shifting: from being thought of as an inevitable process to a potentially treatable condition. Aging is increasingly being viewed as the cause of many diseases and a target for medical intervention. Some longevity researchers, like David Sinclair, actually qualify aging itself as a disease (which, I guess, makes anti-aging treatments eligible to be covered by insurance).

To slow down aging, scientists must first understand what causes it. You may have heard about telomeres: the long repetitive stretches of DNA that cap the ends of chromosomes and get shorter and shorter every time our cells divide. For a while, it was thought that the shortening of telomeres was the cause of aging and diseases like cancer. Today, that hypothesis has fallen out of favor and many scientists (including Sinclair) believe that the cause of aging is not in our DNA but rather in epigenetics.

When the first human genome sequence was published in the early 2000s, we thought we had cracked the code. However, one of the most surprising outcomes of this monumental study was the realization of how little of our biology was hard-coded in DNA and how much it depended on the conditional expression of genes. When it comes to disease, for example, our genetics can be blamed in only about 20% of the cases, while the rest is up to how we live our lives.

This is what the field of epigenetics deals with: it studies how the expression of our genes changes in response to environmental conditions. These could be the things we refer to as “lifestyle factors” such as whether you smoke or not, how much you exercise and where you live. Epigenetics also considers many other variables like the unique biomolecules in each different tissue or cell type, as well as the chemicals circulating in your blood, which change depending on what you eat and what you are exposed to, your hormones, the time of day, stress, diseases, and, of course, your age. All these factors leave a mark on the expression patterns of our DNA via reversible chemical changes called epigenetic modifications.

Our epigenetic signatures, despite not being heritable in the strictest sense (the way our genes are) become semi-permanent with time and can even be passed down to future generations as a “memory” of the environment we lived in.

From a philosophical perspective, epigenetics is a two-faced beast: on the one hand, it gives us hope that we can “overcome” our genes by changing our environment and lifestyle to prevent diseases we might be predestined for. On the other hand, it is the reason why our once perfectly normal genetic programs begin to malfunction as we age.

The unraveling

We are born and die with our DNA pretty much unchanged. It’s the source code that our bodies run on. Every cell has the same set of about 20,000 genes spread between the 23 pairs of chromosomes. Yet, our heart, brain, skin and liver cells could not be more different from each other. This difference is also explained by epigenetics: the different cell types acquire their unique characteristics as some sets of genes kick into full expression while others turn off and become dormant in an embryo in the process of cell differentiation.

While our organs and tissues remain relatively unchanged after we reach maturity, epigenetic changes happen inside cells every day. Epigenetic patterns, or signatures, are much more impermanent than our DNA. As they change throughout our life, errors start to show up in the order of operations encoded by our genes, which results in misshaped proteins, untranscribed genes and other cellular malfunctions that collectively manifest as signs of aging. In a sense, the cells begin to un-differentiate: they “forget” how they are supposed to act and start behaving erratically.

Externally, aging manifests in the way we look and feel, but the root cause is in our cells. You can even tell a person’s age by measuring the presence or absence of specific epigenetic signatures in their tissues or blood. Then the obvious question is: if epigenetic changes are reversible, could there be a way to correct aberrant gene expression? What if we could restore the correct epigenetic patterns in our aging cells? Would they become young again?

Turns out, it IS possible to reverse the damage caused by misinterpreted DNA codes by recovering the epigenetic signatures of youth. This “cellular reset” has been shown to make old mice look younger and live longer, as well as restore vision by reprogramming nerve cells in the mouse retina. Promising results have been shown in humans, too. For example, in one study, a combination of three drugs given over a period of one year was shown to reset epigenetic markers of aging back by 2.5 years.

Could this mean we are on the threshold of discovering immortality?

Stay tuned for the next week’s post to find out!