The Promise of Immortality, Part 2

Drinking from the Fountain of Youth: a modern-day longevity cocktail

If you’ve read my previous post, you would know that some longevity researchers claim that it is possible to reverse the age of our tissues and cells and return them to a more youthful state. Curious to know how? Let’s take a look at some of the research.  

We all know what aging looks and feels like. Yet, we don’t know what causes it. (Time, I know, ha-ha.) On a cellular level, aging is a complex and multifaceted process. Even with all the recent discoveries, we don’t really understand all the changes happening in our cells as we age, much less why they happen. Therefore, anti-aging interventions being developed today are a shot in the dark. Some of them are even contradictory: the same treatments that may be beneficial in the short term may cause negative effects over time. But as with most research, trial and error is how we get to the truth.

First of all, to assess whether anti-aging interventions work, we need to be able to measure their effects. And waiting to see when the person will die is not the most efficient way to do that. This is why scientists have devised a method to measure a person’s cellular age through what’s called an ‘epigenetic clock’, which measures the changes that accumulate in our DNA over time. These epigenetic molecular signatures correlate with the functional changes in the brain, muscle and other tissues.

Most of longevity studies today rely on this simple genetic test to see if the proposed interventions are working. For instance, the study that I mentioned in my previous blog post involved nine subjects who took human growth hormone (hGH), metformin, DHEA, vitamin D, and zinc for a period of 12 months. Their epigenetic markers showed that they were able to shave off about 2.5 years from their biological age. But what does that actually mean? How do the changes in our epigenome translate to functional changes in our bodies? And most importantly, does reversing epigenetic modifications actually restore youth?

Activating our defenses

We can think of aging as different systems in the body starting to malfunction and cause disease. For example, our immune system plays a major role in this process, especially when it comes to cancer. Thousands of mutations happen in our body every day, but the immune system continuously scans for the presence of cells that look wrong and destroys them. This is why the researchers in the study chose the immune function as their primary target.

They administered the human growth hormone (hGH) to the trial subjects is thought to restore the thymus gland function. The thymus gland produces T cells, the immune system surveyors that seek out and destroy sick cells. As we age, the epigenetic changes accumulate in the DNA of the thymus, making the gland “forget” how to do its job. Vitamin D which was used in the study also plays an important role in immune system regulation. In fact, it is a potent epigenetic regulator. Unlike vitamin D, however, the human growth hormone administration comes with negative side effects from joint pain to an increased risk of diabetes and cancer.

Sounds like the opposite of aging reversal, doesn’t it? Generally, anything that makes us grow also makes us age. In fact, there is a new longevity treatment for dogs that specifically targets growth hormone, helping large dogs live longer by suppressing the action of the insulin-like growth factor, IGF-1. So, why would we want to dose fully-grown humans with growth hormone? Could there be a better way to boost the immune system?

Cellular recycling

Another mechanism that protects us from age-related illnesses like cancer is the process of apoptosis and autophagy. Apoptosis is programmed cell death—which is a good thing, even though it may not sound like it. When our cells reach the normal number of divisions they are supposed to undergo (about 50), they die and their contents get recycled. The problems begin when instead of dying, the cells divide uncontrollably (which is cancer) or just sit there, spewing out “a noxious brew of biological signals that can slow cognition, increase frailty and weaken the immune system.”

These are called ‘zombie cells’—or senescent cells, to be more scientific. The signals coming out of these cells cause widespread inflammation and contribute to the development of diabetes, heart and kidney disease and even Alzheimer’s. One way to get rid of senescent cells is by activating autophagy, which clears out the harmful contents of cells. And the best way to activate autophagy is by fasting.

This brings us to the second ingredient in the longevity cocktail: metformin. Metformin is a drug used to treat diabetes. It simulates the effect of fasting by lowering blood sugar and thus mediates the negative effects of the human growth hormone. The health benefits of fasting have been known to humanity for a long time, and cultures where fasting is a regular practice tend to live longer. Intermittent fasting (restricting your food intake to fewer hours a day) and caloric restriction are common in ‘Blue Zones’ where people’s lifespan is significantly longer than average.

These effects are not just correlations. Scientists have deciphered multiple molecular mechanisms that explain why things like fasting and food restriction prolong lifespan. For instance, it activates an enzyme called AMPK, which stimulates autophagy and activates epigenetic modulators that restore gene activity. The same thing can be accomplished through restricting protein intake. When our cells sense a shortage of amino acids, they scavenge and recycle damaged proteins via the mTOR signaling.

Another important family of genes activated by lack of food are called sirtuins. These transcription factors have been shown to prevent DNA damage and epigenetic gene silencing, regulate metabolism and reduce inflammation. Interestingly, many plant active molecules, like resveratrol which is found in the skins of grapes (and red wine) will activate sirtuins. There is even a theory that plants produce these molecules as their own cellular defense mechanism when they experience adversity like droughts. Many molecular pathways are the same in humans and plants, which is why we can get benefits from consuming the anti-aging compounds from the plant pharmacy.

A hormone boost

We have covered food (and lack of it) but let’s not forget about exercise, which provides numerous anti-aging benefits like lowering blood sugar, stimulating blood vessel growth and boosting hormones that keep us young. The longevity drug cocktail in our study included supplementation with DHEA, which has been shown to have a positive effect on lowering insulin, cholesterol and body fat. DHEA is a precursor to sex hormones, and it peaks at around the age of 25. The older we get, the less of these natural boosters we have.

Many people use hormone replacement therapy to delay the onset of age-related effects like graying hair and muscle wasting. However, hormones are potent little molecules and dialing in the precise dosage is hard. Plus, once you start taking exogenous hormones, your body stops producing them on its own. As with many other pharmaceutical drugs, you become a life-long subscriber. Exercise, however, is a natural way to keep up the production of vital hormones in your body. And it’s free :)

The secret ingredient

If you look at each ingredient in the longevity drug cocktail, there is really nothing that special about any of them. In fact, at least one of them is meant to mediate the side effects of the other, which is often the case with pharmaceuticals. Basically, the advice every doctor gives you—eat healthy and exercise—will accomplish the same things as the five compounds prescribed to the participants of the study. The choice is yours: do you want to go the natural route, relying on a healthy diet, fasting and exercise, or take the pill?

If you are really serious about living beyond 100 years, you can probably do both, plus add a few other things to your regimen that promise to increase lifespan. In the next blog post, I will cover some biohacking tricks and interventions that go beyond diet and exercise. Stay tuned to learn the longevity secrets of billionaires and health gurus!