Time is precious. With the multitudinous demands of modern life and our increasingly hectic lifestyles, it can be hard to resist the allure of “time-efficiency” when it comes to exercise. 

“I’ve only got a two-hour window this week,” we tell ourselves, “so I’ll run to the gym, pump some iron, and then run back: that way I’ll make the most of my time.”  

While certainly time-efficient, some evidence suggests that combining different modes of exercise in this way, namely merging strength and cardio into a single session, may in fact be counterproductive for muscle growth. 

Studies looking at concurrent training, whereby subjects immediately follow strength (resistance) exercises with cardio (aerobic / endurance) exercise, have found that it can lead to lower gains in muscle strength, size, and power when compared to strength training alone. Although far from unanimous, these findings suggest that jumping on the treadmill straight after hitting the weight rack may not be the best idea, at least if you’re looking to maximise muscle growth. 

It’s been dubbed the “interference effect” - while resistance training activates signalling pathways that tell your muscles fibres to grow, tacking on cardio exercise too soon afterwards seems to “interfere” with these signals, curtailing muscle growth. 

Although the biological mechanisms underlying the interference effect are not fully understood, it may be down to the response of a special group of cells that drive muscle growth - satellite cells. 

What are satellite cells?

You’ve probably heard of stem cells before - they’re cells that have the capacity to develop into different cell types in the body. 

As embryos, we have stem cells that can differentiate into any cell of the human body, which is fundamental to how we develop from a fertilised egg into a full-blown human. But full-blown humans have stem cells too: adult stem cells. These can develop or “differentiate” into a more limited range of other cells. Our blood and bone marrow, for example, contain blood stem cells, which have the potential to form red blood cells that transport oxygen around the body, or white blood cells that fight off infection. 

Another example of adult stem cells is found in our skin. If you’ve ever hoovered up dead skin from your carpet, it’ll come as no surprise that our epidermis (the top layer of skin) renews itself regularly, roughly every 4 weeks. Underlying (literally) this remarkable ability to repair and regenerate the epidermis are skin stem cells, which, located deeper down in the skin, are constantly replicating (or “self-renewing”) and then differentiating into epidermal cells. 

And so to muscle. Residing in our muscle tissue are adult stem cells known as satellite cells. So-called because they’re located on the periphery of muscle fibres (myofibres), these cells allow us to regenerate muscle tissue. 

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More specifically, satellite cells have the potential to develop into new muscle fibres or to fuse with, repair, and enlarge existing fibres, which is central to how we gain strength and size through resistance training. 

How do satellite cells promote muscle growth? 

Ordinarily, satellite cells lie dormant (to adopt the technical lingo, we say they’re in a quiescent state). When we exercise, however, we subject our muscles to mechanical and metabolic stress, and cause muscle damage, which activates our satellite cells.* 

Once activated, satellite cells start to make copies of themselves and grow in number: a process called proliferation. These activated satellite cells can then fuse with existing muscle fibres and, in doing so, donate their nuclei. 

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^{*Exercise stimulates the release of various signalling molecules from muscle (myokines), such as IGF-1 and IL-6 (the subject of this week’s Inflammation and muscle growth(IL6) report. These signalling molecules are shown to activate satellite cells, promote muscle growth, and help develop muscular adaptations to exercise.} 

As you may recall from your high-school biology lessons, the nucleus of a cell is essentially its control centre. It contains genetic material with instructions for building both a variety of proteins and the machinery that assembles them, ribosomes. Typically, cells have one nucleus, but muscle fibres are a special case, containing hundreds to thousands of nuclei, which we call myonuclei. 

Now, if you were to take a microscope and compare the muscle fibres of, say, Dwayne “The Rock'' Johnson, to that of an untrained person, you would notice that the former’s muscle fibres contain significantly more myonuclei. This is because, through regular weight sessions, Mr. Johnson has activated his satellite cells, which, in turn, have fused with and donated new myonuclei to his muscle fibres. 

These new satellite-cell-derived myonuclei then start to follow their genetic instructions and produce proteins, which leads to muscle growth. It is the assembly of new contractile muscle proteins, actin and myosin, that not only gives us additional strength, but also enlarges the diameter of our muscle fibres, resulting in increased muscle size (hypertrophy)*.

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^{*Interestingly, satellite cells are also proposed to underpin the phenomenon of ‘muscle memory.’ An untrained person will increase the number of satellite cell myonuclei in their muscle fibres with training, gaining strength and muscle mass. If they subsequently stop training for a prolonged period (detraining), they will lose strength and muscle mass but, crucially, retain the higher number of satellite cell myonuclei. This allows them to start producing more muscle proteins when they start retraining, enabling them to regain strength and muscle mass more quickly than the first time round.} 

The extent to which you activate satellite cells depends on what type of exercise and mode of muscle contraction you are performing. 

Resistance exercise, in particular that involving eccentric contraction, is well demonstrated to increase your muscles’ pools of satellite cells and promote satellite cell fusion, resulting in a greater number of myonuclei in muscle fibres. 

Endurance training can also stimulate these processes, although the effect is thought to be less pronounced. It is possible that this is due to lower muscle loading during endurance activities - your leg muscles don’t need to generate as high forces when, say, rotating a bicycle crank thousands of times compared to performing a heavy barbell squat. On this note, studies in mice have shown that greater loading of muscles leads to greater activation of satellite cells. 

But what happens if you combine both resistance and endurance training?

‍What happens to satellite cells when you combine strength and endurance training in one session? ‍

One of the first studies to look at how satellite cells respond to concurrent training  (i.e. combining strength and endurance exercise into a single session) was undertaken by Lyle Babcock and colleagues at James Madison University in 2012.

In the study, eight recreationally-active men performed two different exercise trials. In one trial, subjects performed 4 sets of 10 leg presses and leg extensions (i.e. the resistance training phase) and then, 10 days later, followed this with 90 minutes of cycling (i.e. the endurance training phase). 

In the second trial, the concurrent exercise trial, subjects performed the same resistance training protocol, but this time waited a mere 10 minutes before hopping on the bike. 

To compare the effects of these different training protocols on satellite cells, researchers took biopsies of subjects’ thigh muscles before and after the two trials. They then stained the biopsies with fluorescent dyes and scrutinised them under a microscope, counting the numbers of satellite cells in muscle fibres. This allowed them to assess and compare changes in satellite cell density (the number of satellite cells per 100 muscle fibres) following resistance training, endurance training, and concurrent training.

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As illustrated in the graphs above, whereas resistance exercise (RE) elicited high percentage increases in satellite cell density after 4 days, this effect was much smaller in those undergoing concurrent exercise (CE). This was true for both slow-twitch (MHC I) and fast-twitch (MHC II) muscle fibres. 

So, why the difference in satellite cell activation? 

The researchers postulated that endurance exercise enhances activity of AMPK - an enzyme and signalling molecule that acts as an energy sensor for your muscles. 

During exercise, particularly endurance exercise, our muscles use up fuel. AMPK senses this and activates various signalling pathways that allow our muscles to take up more glucose from the bloodstream and to burn fat for energy. In order to conserve much-needed energy, however, AMPK also sends a signal to inhibit muscle growth. 

When it came to the concurrent exercise trial, the theory is that the strong signals to activate satellite cells and promote muscle growth from resistance exercise were cancelled out, or at least tempered, by the enhanced AMPK signalling elicited by cycling immediately afterwards. In other words, if you do endurance exercise too soon after resistance exercise, your satellite cells receive mixed signals. Should they activate, replicate, and fuse with muscle fibres, or should they stay dormant and allow your muscles to conserve energy?  

It is this mixed messaging to satellite cells that might explain the interference effect. 

Putting things in context

Before you eschew your run to the gym in favour of driving, the above study findings come with important caveats. 

Firstly, we have to interpret the changes in satellite cell numbers with caution. In the 2012 Babcock study, it turned out that subjects already had a slightly elevated number of satellite cells in their thigh muscles before undergoing the concurrent exercise trial. Accordingly, they may have had a more limited capacity to increase satellite cell density during the concurrent exercise trial compared to the resistance exercise trial. 

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Secondly, subsequent studies haven’t actually found any differences in satellite cell activation between resistance, endurance, and concurrent training. For example, as illustrated in the graphs above, a 2021 study in which subjects underwent either 12 weeks of resistance (RES), endurance (END), or concurrent training (CET) reported no appreciable difference in satellite cell content between the different exercise modalities. Similarly, a 2018 study found that tacking on a HIIT (high intensity interval training) workout to the end of resistance training does not appear to curtail any increases in satellite cell number. 

OK, so combining endurance and resistance exercise into one session may not necessarily impact satellite cell activation, but it still impairs muscle gains right? There still appears to be an interference effect, correct? 

Yes, but it may not be as large as you think. A 2022 systematic review and meta-analysis of 15 studies found that concurrent training has a small negative effect on muscle fibre hypertrophy compared to resistance training alone. 

Interestingly, this interference effect was more pronounced in slow-twitch (Type I) muscle fibres and when following resistance exercise with running (as opposed to cycling). This may be because running involves more repetitive eccentric muscle contractions, leading to greater inflammatory muscle damage post-exercise. The resultant inflammatory environment of muscle cells may then dampen down the signals for muscle growth elicited by resistance exercise. 

Overall, however, the negative impact on muscle fibre hypertrophy was found to be relatively small. Moreover, health and fitness, as with every other aspect of life, is all about trade-offs. Both resistance and endurance exercise of course have multiple benefits for muscular and overall health - so, if time is of the essence, it’s probably still better to merge strength and cardio into one session than forego one completely. 

All that said, if minimising the interference effect and maximising muscle growth is your number one goal, the following tips may help:

• Perform endurance and strength training on different days.

• If you do have to perform both on the same day, do your endurance workout first. 

• Ideally try to space the sessions out by a few hours. You could run in the morning, for instance, and then hit the weights in the evening. 

• If you do immediately follow resistance training with endurance exercise, opt for cycling or elliptical training over running. 

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Image references

Babcock, L., Escano, M., D'Lugos, A., Todd, K., Murach, K., & Luden, N. (2012). Concurrent aerobic exercise interferes with the satellite cell response to acute resistance exercise. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 302(12), R1458-R1465.

Bruusgaard, J. C., Johansen, I. B., Egner, I. M., Rana, Z. A., & Gundersen, K. (2010). Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proceedings of the National Academy of Sciences, 107(34), 15111-15116.

Carnes, M. E., & Pins, G. D. (2020). Skeletal muscle tissue engineering: biomaterials-based strategies for the treatment of volumetric muscle loss. Bioengineering, 7(3), 85.

Shamim, B., Camera, D. M., & Whitfield, J. (2021). Myofibre hypertrophy in the absence of changes to satellite cell content following concurrent exercise training in young healthy men. Frontiers in Physiology, 12, 625044.

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