How Big Gains Can Fix Your Brain


How Big Gains Fix Your Brain

Read Time: [7-10 minutes]


  • Exercise is a strong anti-depressant but the mechanisms were unclear as to why
  • PGC-1α1 is a gene well known for muscle growth, but is now showing an anti-depressive effect

  • How does PGC-1α1 protect your brain?
  • Important Notes


It’s no secret that exercise is an effective way to deal with depression. In fact, the prestigious Cochrane Database showed that exercise can have just as strong an effect on depressive symptoms as anti-depressants and psychological therapy.

While long distance running seems to be the tool of choice for most people to fight the depression bug, there may be a role that resistance training can help as well. A recent study gives us a big reason to believe that muscle can be a powerful defender for brain health.

More Than Meets the Eye

We once thought that muscles were dumb tissues that obeyed the bidding of the nervous system. In recent years, researchers are showing that muscles can act like a gland in the endocrine system and release chemicals that manipulate your body chemistry.

Exercise causes muscles to produce a compound called PGC-1α1 (pronounced PGC 1 alpha 1). The name is not as important as what this compound does. PGC-1α1 plays a big role in muscle physiology. Every time you exercise, the genes that produce PGC-1α1 become upregulated to help the muscle prepare grow and become stronger. Some of it’s functions include:

  • Blood vessel formation to support muscle conditioning
  • Mitochondria formation for increased energy production
  • Help form more neuromuscular junctions (places where nerves meet muscle tissue)

That’s all well and good, but that only describes the effect on muscle tissue, but what about the effects on the brain?

A 2014 study in the journal Cell showed that PGC-1α1 helps to protect against a chemical that causes stress related depression.

How Does It Work?

Whenever your body is under stress or a heightened state of inflammation, your liver produces a compound called kynurenine (Kin-your-eneen) into your blood stream. Unfortunately, kynurenine is a proinflammatory molecule that is capable of passing the blood-brain barrier.

Generally speaking, your brain tissue hates inflammation, and inflammation in the brain is linked to clinical depression. If your blood-brain barrier can’t keep kynurenine out, then the body needs a different way to deactivate this chemical compound.

That’s where your muscles come in with PGC-1α1 to save the day. The image below comes from the article and shows the impact that exercise has on muscle and PGC-1α1.

Image from Cell Journal

Image from Cell Journal

PGC-1α1 produces a compound called KAT (kynurenein aminotransferase). KAT acts like a filter for kynurenine and turns it into a harmless chemical. It’s like a built in detoxification system.

When the authors studied this in rats, they found that rats who were unable to produce PGC-1α1 while being exposed to chronic stress showed increased depressive behavior, while the control rats were protected.

Obviously you’re not a rat so how do we know this applies to humans?

Kynurenine has a long track record of causing problems in the brain which include diseases including Huntington’s Disease, schizophrenia, and depression. This review paper summarizes the effect of Kynurenine in all mamallian brains, including humans.

We also know that reduced PGC-1α1 production in humans is associated with cancer, diabetes, and other metabolic disease. We also know that PGC-1α1 tends to decline as we age which may help explain why aging can impair brain function as we get older.

So how do we know that exercise can reduce the effects of kynurenine?

A group of willing volunteers (college students) signed up to have their leg muscles to be biopsied. Because only college students would willingly have a scientist put a needle in their leg and extract some muscle tissue for $20.

After putting them through a 3 week exercise regiment, they biopsied the muscles again. The result?

  • Muscles showed an increase in PGC-1α1
  • Muscles showed an increase in KAT to help break down kynurenine

Great! So far so good. Now the studies on PGC-1α1 are primarily associated with endurance training in humans and mice. Treadmills and cardio….the nemesis of most weightlifters. Can muscle building and strength training derive these brain sparing benefits?

Big Gains to Help Your Brain

PGC-1α1  has a cousin named PGC-1α4. A study in the same journal showed that PGC-1α1 is associated with endurance while PGC-1α4 shows up during weight training. PGC-1α4 is what starts the process of hypertrophy and muscle gain. [Source]

Although the study was focused on PGC-1α4 expression, the authors also found that resistance training increased PGC-1α1 too! In fact, when you COMBINED resistance and cardiovascular exercise (like one might see at Crossfit), then you have the greatest production from these genes.

Chart from study Arrows are my own insertion

Chart from study
Arrows are my own insertion


So resistance training and muscular gains are associated with the production of this compound that fights depression. Best of all, if you combine the two, then you may get even better protection.

 Important Notes

  • Depression is a multifactorial disease. Just because you exercise and are muscular doesn’t mean you you won’t suffer from depression. However, as with every lifestyle modification, it never hurts to stack the deck in your favor!
  • This is not about blaming depressed people for not exercising. This is a call to use exercise as a treatment to help fight a known chemical cause of depression.
  • If increased muscle is protective against brain inflammation and we know old age is associated with decrease muscle mass, can we fight diseases of old age by simply maintaining lean muscle mass? I think it can.

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One Stunning Image That Redefines What We Know About Aging

One Stunning Image That Redefines What We Know About Aging

One of the coolest things about social media is the way that it allows you to learn and interact with people that you may never have interacted with in the past. Using sites like Twitter and Facebook have given us unprecedented access to follow our favorite athletes and celebrities, and actually give them an opportunity to interact with you.

I’m not really a celebrity type guy, and I don’t really get too star struck, but I do geek out over the chance to follow and interact with people that are smarter and more innovative than I am. It allows me to see what other practitioners are doing, and gives me the chance to give my patients better care.

One of these guys is Dr. Brian Tiu. Brian is a Structural Chiropractor in Seattle that has a strong background in sports. If you’re not following him on Twitter, make sure you do today. Lots of good free stuff from him on a daily basis. You can find him here.

Anyway, here’s one of his posts that came across my newsfeed that really blew my mind about exercise and lean muscle mass:

If you missed the arrows, the white part of the image is fat tissue, and the dark gray parts are muscle. That’s amazing! The fact that men in their 70’s could maintain their muscle mass, prevent fat from invading muscle tissue, and maintain a level of fitness to run in triathalons is simply phenomenal.
The image is taken from a study that compared the muscle composition of chronic exercisers (they couldn’t find a better term for this? Really?) versus healthy controls. They performed MRI studies on the thighs of both groups and evaluated fat to muscle ratios and how much fat had infiltrated muscle tissue.
Before I talk about the results of the study, let’s make sure to mention this.

Conventional Theory

Current theories on aging  simply state that muscle mass will fade once you hit the age of 30.  Once you hit the age of 40 you start losing about 1% of muscle mass per year. Once you hit 70, you may lose an average of 15% in 10 years.

Here’s what happens to people as they lose muscle mass:

  • Increase in overall mortality
  • Osteoporosis
  • Increased risk of fractures
  • Increased risk of disability
  • Use assistive devices (canes,wheelchairs)
  • Poor balance and prone to falls

Essentially, a bulk of the problems associated with aging.

Now it’s a bit silly to say that you can stop the clock, and stop the body from getting older. That’s why I’ve always found the term anti-aging to be rather silly. However, with that being said, aging is so profoundly affects quality of life, that we should be encouraged to use tools to mitigate their effects.

When you’ve finally reached retirement, you have the freedom to see the world, time take on hobbies, and ability do things that you didn’t have time or money for in your earlier ages. Why would you want to spend those years with immobility, wheel chairs, and fearing the next fall?

The problem is that these studies were focused on people that were reported as “healthy” because they didn’t show any symptoms….(because symptoms are the only thing that matter in health….a topic I’ll tackle on another day).

The Study

The study was published in  The Physician and Sports Medicine in 2011. The image that they use in the journal article is actually even more striking than the one in Dr. Tiu’s post above. Let’s take a look.

Image Credit: Wrobleski et al. The Physician and Sport Medicine. Volume 39 Issue 3. 2011

Image Credit: Wrobleski et al. The Physician and Sport Medicine. Volume 39 Issue 3. 2011

The bottom two images are the leg muscles of 2 men in their 70’s. You can see that the sedentary man muscles are atrophied, and there’s actually bits of fat in the middle of gray muscle tissue which indicates that the man’s muscles are becoming less functional. The top image is a thigh of a man in his 40’s.

Now if you compare the image of the 40-year-old thigh versus the 70-year-old thigh you can see that the muscle density is pretty similar. So in a span of 30 years, where muscle mass should have dropped about 25%, the 70-year-old athlete was able to maintain just about all of his muscle.

What Does This Mean For You?

This study looked at people who are sedentary and compared them to people who do some pretty intense training for triathalons. You’re basically looking at polar opposites in terms of what someone’s day to day life looks like. One is doing almost no exercise at all outside of what it takes to live, the other is probably running, swimming, biking, or weight lifting multiple times a day, a few days a week.

What does this mean for the casual exerciser? Can you achieve similar results if you start exercising later in life?

It’s hard to say just from this study, but my guess is that you can still achieve great muscle mass without triathalon levels of training. The key is finding the right exercise for you, and using that as a way to be consistent. Here are some tips:

  1. Learn to love squats – most of us are probably worried about how squats can affect your back or your knees. I’ll address some of those concerns in another post, but just know that squats can be done safely to take advantage of some amazing benefits.Squatting stimulates the release of growth hormone and induces muscle hypertrophy better than almost any other exercise around. Finding a good trainer and getting on a regiment of squatting 2 times a week can make some dramatic changes in your body composition.
  2. Find Movement You Love – Not everyone enjoys working out and running. The truth is if you dread your exercise routine, you will give up on it before long, no matter how dedicated you are. Movement is more important than the concept of exercising. Moving our bodies is like food for our brain and our muscles. Some people love dancing. Some love rock climbing. Others enjoy going on a bike ride in the city. Lots of my patients just like working in a garden. All of these activities can help you maintain some level of muscle mass and reduce fat infiltration. It may take a LOT more dancing, biking, and gardening to achieve the same outcome as a good gym regiment, but at least you know that you’ll keep going.
  3. Give Yourself Something to Work For Multiple Times per Year – Human beings are driven by excitement and enthusiasm towards a goal. Here’s a short list of ways to use a goal to drive an exercise program you love to do:

    Runners/Bikers/Swimmers – compete in a 5k/half-marathon/triathalon 2-3 times per year so that you are always working towards a race.

    Gardeners – choose a project you want to accomplish for your home once per year. You’ll be kept busy by regular up-keep as well

    Dancers – look into local competitions so you can focus on improving your skills and find a platform to show off once in a while

    Outdoor enthusiasts – don’t like exercising, but you enjoy being outdoors. Check out sites like to find groups that have your same interests. There are almost always groups that have get togethers for hiking, beach yoga, and a variety of other activities

Your ability to move is tied directly to your health as you age. The big key is turning our activity into things that we enjoy so that we can turn that into a sustainable habit that will be with us through our lives.

There are even new thoughts in the scientific community that believe muscle can serve as protein storage houses for building antibodies, a key tool in immune function. When we lose muscle mass, we lose one of the building blocks of our cells and immune function.

Don’t fall into the trap of people selling you anti-aging creams, juices, and miracle supplements. The most valuable nutrient you can have in your life, is free, and you can take it everyday. All you have to do is get up and move.

Did you like this article? Feel free to share it with the people you care about and see if a Complimentary Consultation is the next step to regain their health.

Dr. Chung is a practicing Structural Chiropractor in the West Palm Beach area. He has been published in peer reviewed scientific journals and is a sought after speaker in health and wellness. Follow his blog at or find him on twitter at @drjonathanchung