Getting Fit With An Exercise Pill?

How Close Are We To The ‘Holy Grail’ Of Health?

Aaryan Harshith
7 min readAug 2, 2020

Judging from the fact that most of us aren’t ultra-marathon finishers or world-class pole-vaulters, exercise clearly isn’t enjoyable. If the sweaty, out-of-breath feeling isn’t enough to keep you away, don’t forget about always waking up sore, getting injured, or just how much time a routine like that can take.

Workouts suck (for most of use, at least). But unless you’re already an athlete or work an intensely physical job, there’s no other option if you want to stay healthy. But with modern science, we’re getting closer to a workaround — so you’ll need to worry more about going to your pharmacy than buying a treadmill to stay fit.

The Wonders Of Working Out

Before we go on trying to crack the problem of having to exercise all the time, it helps to know what exercise is, and why exactly we do it:

Well, you’ve probably already figured out the obvious reasons, like burning fat and staying healthy for longer. But there’s a whole bunch of other aspects to how working out can make our lives better. In general, though, the benefits of exercise fall into three categories: muscular, cardiovascular, and mental.

Exercise helps us because it puts these three aspects of our bodies under temporary stress. Whether that’s weight-training to stress your muscles or going on runs to work your heart, your body goes through a healthy amount of damage and grows back stronger. Repeat that cycle of destruction and repair enough, and you’ll eventually get more fit. It’s that simple.

But what if you didn’t need to exercise to reap those gains?

A Tale Of Two Mice

Let’s begin with the story (study) of two mice — Couch Potato Mouse and Lance Armstrong Mouse. Both grew up in a lab-adapted version of the “standard” American lifestyle. In this case, that meant a whole lot of food and not a lot of exercise.

Couch Potato Mouse (as his name suggests) was the epitome of a couch potato — and you can’t blame him. What else would a mouse do if it lived in a cage with nothing but a giant bowl of food in it? Couch Potato Mouse wasn’t fit, and it showed:

One of the unlucky mice forced to exercise during this experiment. Source

Sections from the study reported that Couch Potato Mouse looked much older than other mice his age. His hair was sparse, his actions were slow and lazy, and he was well above overweight. Humans experience similar effects, too.

On the other hand, you could take a look at Lance Armstrong Mouse and question if he even lived under the same circumstances. He looked no short of a mouse-athlete! He looked younger and was considerably more fit than an average mouse could ever hope to be.

But why? What made Lance Armstrong Mouse so much healthier than Couch Potato Mouse, even though they grew up in the same environment? The only change was a daily dose of a “magic” drug.

GW501516 (516 for short) was the wonder drug in question — developed by Prof. Ron Evans from the Salk Institute in San Diego. It works by “copying” the effects exercise has on the PPAR-delta gene — a part of your DNA that tells your body how to divide and convert your food into energy.

So when drug 516 binds to PPAR-delta’s receptor, its composition magnifies the signal the gene sends to burn fat and prevents your body from burning sugars (carbohydrates)-our body’s best source of power:

Prof. Evans on his team’s discovery of drug 516. Source

When Evan’s team administered drug 516 to Lance Armstrong Mouse, his endurance spiked, while his insulin-resistance (a marker for diabetes) and waistline dropped to healthier levels as well. With just eight weeks of therapy, the group of Lance Armstrong Mice outran their Couch Potato pals by over an hour and a half, on average.

It was one of the first displays of how our bodies could bypass the need for activity (and physical training in general), with a drug. And ever since then, the developments never stopped.

The Strongest Flies In The World

Now, on to more recent study conducted on (you guessed it) flies! This experiment, performed by the University of Michigan, aimed to decode the effects of exercise on specific genes in our bodies.

You might have never heard of it, but Sestrin is one of the most valuable proteins in our bodies. It’s thought to be responsible for the variety of perks you get from exercising, like more muscle mass and endurance. Research shows that when our muscles go through stress (like after working out), Sestrins rush towards the area.

That made the scientists from the University of Michigan wonder if they could use the protein to accelerate the flies’ abilities while exercising. Or even better — get them to maintain their fitness without having to at all.

The test was simple. Prof. Jun Hee Lee’s team dropped two groups of common drosophila fruit flies in a test tube, knowing that their instincts made them crawl back out.

To test their endurance, the group installed a fly-sized treadmill inside the tube to resist their climb. The longer the fly stayed on without tiring out, the higher its level of fitness, and vice versa.

If fly-sized treadmills weren’t cool enough, here’s where things get exciting. Just like Couch Potato Mouse and Lance Armstrong Mouse, one of the two groups received a dose of Sestrin throughout the trial.

The others were genetically-edited to stop producing any at all. All of the flies went through the gruelling “treadmill trials” for three weeks — the only question left was: “Did the drug have any effect?”

**Caution: What you’re going to read will sound insane — just a heads up.**

Well, the study’s in the article for a reason — it worked! Sestrins did such a great job at enhancing the flies’ fitness that some of them outperformed the others by over 100%. That’s like an average person waking up and suddenly winning a 5K race:

How Sestrin is able to work wonders (at least on flies). Source

And according to the paper, that increase in endurance wasn’t normal. Rather than a slow development in how long the flies could last, a dose of Sestrin spiked the flies’ fitness to almost their maximum potential capacity in just a few days.

As surprising as those strength statistics are, the outlook still isn’t straightforward. Will a Sestrin-based drug ever work on humans? Nobody knows. But with the results so far, the future does look promising.

The Missing Piece

Even though we’re just starting to learn about the process, we know there’s potential to mimic (and even surpass) almost all the physical benefits exercise can have. But what about the mental aspect?

Don’t forget — exercise stresses your brain in some ways, too. Its benefits stretch much further out than just your body — the dopamine and serotonin that you release during a workout can positively impact your mood and your mind. But naturally, an organ as complex as the brain is just as hard to decode. Until now.

Studies have shown that some of the compounds and proteins our livers produce can influence the brain. One of those proteins happens to be GPLD1 — an enzyme our liver generates during exercise.

You can think of them as “molecular scissors” that snip molecules off cells and set them free to go about their work. Theories suggest that they influence the brain — possibly by changing the composition of our blood and letting our brain release the right neurotransmitters.

That’s something we’ve known for a while now — nothing special. But Prof. Saul Villeda’s research team managed to pull off something unique with that old tidbit of information.

It started with the realization that mice who exercised regularly had better mental performance, as well as proportionally higher levels of GPLD1 in their blood plasma. On the other hand, old or sedentary mice fell closer to the opposite end of the spectrum.

Using a group of old mice as test subjects, the group took the blood-plasma from young, well-exercised mice, and injected the concoction into them. Reports showed that the older mice began to show significant improvement in their critical thinking, memory retention, and processing abilities:

A closer look at the GPDL1-rich ‘vampire’ blood of mice. Source

And the cherry on top? We’ve seen uncannily similar results in early human tests. Just like the mice in the experiment, humans showed identical spikes in the enzyme after exercise and happen to have higher levels of mental sharpness compared to the rest of the population.

But still, GPLD1 might not be the golden ticket we’ve been on the look for. We haven’t fully linked GPLD1 to exercise, and we still don’t know if the enzyme is safe for use. Some research even suggests that it might be linked to diabetes and other insulin-related diseases. The search is far from over.

But then again, this is just the beginning.

The Verdict?

Pretty cool, huh? All those studies have the potential to change the game. Together, they might just pave the way to a future where exercise becomes obsolete.

Who knows? It might be the next Apple-Esque revolution — maybe in the next decade or so, exercise pills might become the new multivitamins. But for now, exercise is something we’re going to have to bear with for a little while longer. Just kidding. Make sure to stay healthy anyway.

Thanks for reading, and stay safe,