The Molecules Your Muscles Release That Can Rewire Your Brain

If you’ve been with me here for a while, you know my goal is straightforward: share ideas that help us get better—mentally, physically, and professionally. Lately, as I’ve been digging into the research for my upcoming book, I came across something so powerful I couldn’t keep it to myself. 

What follows is a look at the latest research, the evolutionary biology behind it, and most importantly, what it means for how we live today.

Publicly, it started last week when I shared a short clip of Stanford health psychologist Dr. Kelly McGonigal. It’s already been viewed more than 2 million times. One of the most-liked comment captured some of the inevitable pushback perfectly:

“What a load of BS, dude.”

What set people off was her use of the phrase “hope molecules.” I get it. It sounds like fluff. But the science is anything but. In fact, it may be one of the strongest reasons doctors worldwide now prescribe exercise as treatment for depression and anxiety. Study after study shows it can be as effective as medication or therapy for many patients—and the molecular biology finally explains why.

When our muscles contract, they don’t just move us. They release proteins, these “hope molecules” called myokines into the bloodstream. These proteins can cross into the brain and directly influence how it functions—boosting mood, resilience, memory, and long-term brain health.

So let’s dig into the biology. This is where the research makes it clear: movement doesn’t just change our bodies—it rewires how our brains function.

The Breakthroughs That Changed Everything

I first brushed up against this research while studying exercise science back in the late ’90s at the University of Florida… somewhere between track training and some rough nights at The Swamp and the Grog House (my two favorite bars).

One of the molecules being studied then was interleukin-6 (IL-6). At the time, it had a bad reputation (not too dissimilar from the Grog House). IL-6 was known only as an “inflammation signal,” something the immune system released when we were sick or injured. If it showed up, it meant our body was in trouble.

Then in the early 2000s, researchers made a discovery that flipped the script: our muscles release IL-6, too. And when it comes from muscle, it behaves differently—calming inflammation and regulating metabolism instead of fueling it. That was the first real clue that muscles aren’t just engines for movement. They’re also messengers, secreting proteins that affect the entire body, including the brain. These proteins would later be grouped under a new name: myokines.

Why Our Bodies Do This

From an evolutionary perspective, this isn’t random—it’s survival. For most of human history, when our muscles were working hard, it wasn’t for fitness or recreation. It meant something critical was happening: hunting food, fleeing a predator, traveling long distances, or fighting to protect our group.

In those moments, moving our bodies wasn’t enough. Our brains had to rise to the challenge too. We needed sharper memory to remember where we’d seen food or danger before. We needed focus and calm under stress to make quick decisions. And we needed resilience, both physical and psychological, to keep going when things got hard.

That’s where muscle-brain signaling comes in. When our muscles contract, they send out chemical messages that essentially tell the brain: “Pay attention. Store this information. Don’t give up. Adapt to what’s coming next.”

• From a biology standpoint, this helped keep inflammation under control so we could survive sustained effort without burning ourselves out.

• From a psychology standpoint, it hardwired resilience into our system — so that exertion came with built-in mood regulation and stress protection.

This link between movement and mental state is no accident. It’s an ancient adaptation that allowed us to survive in unpredictable environments. And today, even though we’re no longer running from predators, the same wiring is still at work every time we move.

It’s as if our muscles evolved to double as a pharmacy, dispensing the exact chemicals our brain needed to survive high-stakes situations. Modern research has now put names to dozens of these Myokines proteins. Three stand out: Irisin, Cathepsin B, and IL-6—each playing a different role in how movement shapes our brain and mental health.

Why It Matters

I’ve written before about the power of stacking reasons to motivate ourselves—don’t just exercise for strength, or weight, or energy. Add reasons together until they become undeniable. This science gives us one of the strongest reasons yet: movement changes our brain.

• Mental health: Driven by Irisin, exercise boosts Brain-Derived Neurotrophic Factor (BDNF), one of our body’s strongest natural antidepressants. Low BDNF is tied to depression and anxiety.

• Resilience: Muscle-derived IL-6 calms inflammation and prevents stress from spiraling out of control.

• Cognition: Myokines improve memory (Cathepsin B being a major player) learning, and focus—lasting upgrades to brain performance.

• Longevity: These pathways protect brain health over time, lowering dementia risk and keeping us sharper as we age.

So when we think about exercise, we should stop reducing it to calories or muscle tone. It’s one of the most direct levers we have to change how our brains feel and function—right now, and decades from now.

My Experience: Gold Medals to Rock Bottom

When I was training for the Olympics, I assumed workouts were just about strength and speed. Only later did I realize they were also building my mental resilience by constantly flooding my system with myokines.

Years later, when I went through depression, I saw it from the other side. On my lowest days, I scaled back from a 30-minute ride to a 10-minute walk. Some days, just stretching. It absolutely felt like failure at the time.

But now I know: even those tiny movements were releasing myokines. My body was still sending signals to my brain to repair, adapt, and keep going. Science has confirmed it—any muscle contraction, no matter how small, produces chemical changes that support brain health.

What To Do With This Knowledge

We don’t need to train like Olympians to get these benefits. We just need to move.

3 Ways to Apply This Today

1. Micro-movements count: Walk the stairs, carry groceries, do a few squats. Small contractions can make a real difference, especially if you’re in a bad place mentally.

2. Pair stress with movement: When stress builds, move — go for a walk, stretch, or do pushups. It changes our chemistry on the spot.

3. Think long-term: Movement today isn’t just for energy. It’s building the foundation for brain health and resilience decades from now.

Final Word

Some people will always love the phrase hope molecules. Others will always hate it and try to call bs. But the label isn’t what matters.

The science is clear: our muscles are constantly talking to our brain. Every contraction is sending a message: repair, grow, adapt, keep going. And it makes complete sense in the context of how we evolved.

Every time we move, we’re not just exercising our bodies. We’re changing our brains.

And that’s something worth listening to.

- Steve

And for those with BS detectors or curiosity, here’s some references for you:

• Muscle–Organ Crosstalk: The Emerging Roles of Myokines: A broad overview

• Wrann et al., Cell Metabolism, 2013: Irisin & BDNF

• Moon et al., Cell Metabolism, 2016: Cathepsin B & memory

• Pedersen & Febbraio, Nature Reviews Endocrinology, 2012: Muscle as a secretory organ

Back to article

steve.mesler

35K followers

View more on Instagram

Back to article