How an unhealthy gut causes muscle loss

Muscle loss is a tremendous problem as we age. This process, known as sarcopenia, starts at around age 30 and proceeds at a rate of around 3-5% of your muscle mass every decade.

There is no way around this, it will hit us all. And, unfortunately, it plays a major role in our eventual demise.

As we become more frail, our risk for injury skyrockets. A minor slip on the sidewalk that wouldn’t phase us when we’re young sends us to the hospital. Consequently, many won’t leave the hospital alive.

On the other hand, physical frailty isn’t the only problem to consider. Muscle functions as an endocrine organ, sending signaling molecules known as myokines to every other system in the body. These signaling molecules, known as myokines, help quash inflammation and bolster our defenses against pathogens.

Moreover, resistance training is linked to functional and structural improvement in the brain. These changes lead to improvements in executive and overall cognitive function. And in those with Alzheimer’s disease, higher muscle mass is independently associated with less brain atrophy.

It’s clear that maintaining a resistance training program is the most important factor for maintaining muscle mass as we age. Alternatively, hobbies and/or a job that regularly stress muscle do the trick as well.

But other factors help stem age-related muscle loss too. A new review positions the gut microbiome as central to mitigating age-related muscle loss.

In today’s blog we first discuss this review, then the things we can do to stem the tide of age-related loss of muscle mass.

Anabolic resistance and muscle loss

As you are likely aware, anabolic hormones such as testosterone and growth hormone decline as we age. While this leads to a reduction in muscle mass, it’s not the only problem we have to deal with.

As we grow older, the same dietary protein intake leads to lower muscle protein synthesis. We call this anabolic resistance, and decreased testosterone and growth hormone play a role.

But there are other factors at play here, as discussed in a wonderful review published recently. These factors include:

  • Impaired protein digestion and absorption
  • Decreased amino acid synthesis via the microbiome
  • Enhanced amino acid breakdown via the microbiome, gut and liver

These 3 factors reduce the amount of serum amino acids available for muscle protein synthesis. Additionally, increased inflammation and microbial metabolites impair muscle protein synthesis by:

  • Decreasing anabolic hormone production/signaling
  • Impairing insulin signaling
  • Altering mTOR signaling, which functions as an anabolic switch

All of these factors play a role in speeding up muscle loss as we age. Most importantly, the authors make the point that age-related changes to the microbiome come along with these changes.

How the microbiome promotes muscle loss

It’s clear that one of the important ways the microbiome impacts muscle loss as we age is via controlling systemic inflammation. As you are probably aware, with aging, systemic inflammation increases. This may be a result of a drop in microbes that produce short chain fatty acids, butyrate in particular.

Butyrate acts as an anti-inflammatory and is the primary fuel source for the cells that make up the intestinal barrier. Consequently, decreased production of butyrate by the microbiome may lead to increased intestinal permeability and cause bacterial components such as endotoxin to enter the blood.

There is some evidence of this being detrimental to muscle mass in humans. Firstly, people with sarcopenia have a reduction of SCFA-producing bacteria compared to healthy controls. Secondly, there is an increase in bacterial components in the blood as we age known as metabolic endotoxemia, and this leads to signaling in muscle that can impair muscle growth.

Furthermore, a study in healthy young men found that infusing them with endotoxin led to a significant decrease in testosterone through increased inflammation.

Other factors are important as well. Lysine is an important amino acid in protein turnover, and microbes that make it decline with age. Leucine is another important amino acid for muscle growth as it plays a role in anabolic signaling.

The microbiome contributes ~20% of the leucine in blood, and as we grow older, more leucine gets oxidized by the gut, liver, and microbiome. This leaves less leucine available to promote muscle growth.

Overall, it seems the microbiome may be an attractive target to slow age-related muscle loss. But is it the chicken or the ege?

Shaping a healthy microbiome

One of the more frustrating aspects of helping people understand the gut and microbiome is how they think the whole operation works. For example, one idea is that one day obese people will be able to take a probiotic pill that will populate their gut and help them get to and maintain a healthy weight.

The thought process here is that the microbiome is the primary driver in the gut-microbiome-brain axis. In other words, I have condition X, and I’ll be able to take probiotic Y which will cure me of condition X. The problem is, we don’t have evidence in humans that probiotics/suppplements are the therapeutic approaches to nudge it in the right direction.

It’s just as likely that a healthy microbiome is a biomarker of a healthy gut, and a healthy gut is driven by a healthy lifestyle. And we do have data in humans to support this. For example, gut microbiome composition and diversity is associated with sleep physiology, but that doesn’t mean taking a probiotic will help you sleep.

It means people who sleep well have what is considered to be a healthier microbiome. So if you want a healthy microbiome, prioritize sleep and practice good sleep hygiene.

Diet and exercise are 2 other important factors that associate with a healthy microbiome, particularly SCFA production. But, again, there is likely more push from those habits producing a healthy microbiome than a healthy microbiome pushing performance in those habits.

Our microbiome evolved with us and the internal conditions our environment created. Our current lifestyle simply isn’t doing us any favors in supportins a healthy microbiome.

How aging stacks the cards against us

The fundamentals essential to gaining muscle when you’re young are the same fundamentals essential to preventing muscle loss as you age. This includes:

  • Strength training: Far and away most important
  • Sleep
  • A balanced diet high in protein
  • Stress management
  • Limit alcohol intake
  • Butt-chugging coffee(Sike!)

But, the stakes are raised a bit in older individuals. A large chunk of this is behavioral, and these behaviors promote age-related changes in the microbiome.

muscle loss and the microbiome

This includes a poor diet low in fiber and protein, less physical activity, less exercise, and poor sleep. Interestingly, total sleep deprivation was recently shown to decrease muscle protein synthesis in humans by 18%.

Another major factor is circadian disruption, which becomes more common as we age. This means we have to work harder to send the right signals, and staying up all night, being sedentary, and eating junk food aren’t the appropriate signals. This almost certainly speeds up age-related muscle loss.

Muscle protein synthesis is under circadian control, with greater synthesis during the active period and greater catabolism at night. Moreover, this rhythm persists in inactive muscle, so synchronizing activity with this rhythm may help maintain muscle mass in older people.

It’s clear that we can get away with some poor habits and still build muscle when we’re young. But the physiological changes that happen as we age cut away at this margin for error.


As we age, our physiology changes in a way that causes a priority shift with regard to muscle mass. During puberty and development, we can put on muscle mass with ease, even when our habits aren’t the best. But as we get older, we have to shift our focus more toward maintaining muscle mass by slowing down muscle loss.

Lifelong strength training, or at least stressing muscle in a way that promotes growth, is crucial to preventing frailty when we’re older. But you’re never too old to get started and see the benefits of strength training.

Fortunately, the same fundamental principles that promote muscle gain when you’re young will help prevent muscle loss as you age. This includes regular strength training, a balanced diet, good sleep, strong circadian rhythms, managing stress, and limiting alcohol. Oddly enough, these are important aspects of our lifestyle that affect our microbiome.

You’ll find a vast array of articles on this blog about these topics. The best place to start would be heading to the homepage and going through the blogs and podcasts there. You can do that by sliding on over here.

There’s also a new course coming soon, so stay tuned!

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