Physiology Friday #251: Does Our Body Have a ‘Muscle Memory’ for Aerobic Exercise?
The maintenance of molecular changes after high-intensity training refute the idea of "use it or lose it."
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Muscle memory is a concept in exercise science that highlights the remarkable ability of muscles to "remember" prior training, allowing for quicker adaptations when retraining after a break. While often associated with skill retention, like cycling or swimming, muscle memory extends beyond motor skills into the cellular and molecular processes that govern how muscles grow and function.
The concept of muscle memory is quite simple: It suggests that our body will have an enhanced response to a specific exercise stimulus (i.e., resistance training) when that exercise stimulus has previously been encountered in the past.
If you’ve lifted weights before, you should be able to gain muscle mass and strength faster than someone who’s never lifted weights.
In resistance training, muscle memory is well-documented and is driven by two primary mechanisms: myonuclear retention and epigenetic modifications. Resistance training stimulates muscle fibers to increase their number of myonuclei—specialized nuclei that regulate growth and repair. Research has shown that even during periods of inactivity when muscle size decreases, these myonuclei persist, providing a framework for rapid muscle regrowth during retraining. Additionally, resistance training creates epigenetic changes, such as modifications in DNA methylation, that "bookmark" the activity of genes essential for muscle repair and adaptation, ensuring muscles are better prepared to respond when retraining begins.
Does muscle memory exist for aerobic exercise adaptations?
While the role of muscle memory in resistance training is well understood, its application to other types of exercise, like aerobic or endurance training, is only beginning to be explored. Unlike resistance training, which focuses on hypertrophy and strength, endurance exercise training drives improvements in metabolic efficiency, cardiovascular capacity, and mitochondrial function.
We know that endurance training improves these markers dramatically. A lack of training, or detraining, also has remarkable, but not so enviable, effects. This was illustrated in a classic study known as The Dallas Bed Rest and Training Study.
Conducted in 1966, The Dallas Bed Rest Study provided a striking look at the effects of prolonged inactivity and subsequent endurance training on cardiovascular health. In this study, five healthy 20-year-old men underwent three weeks of complete bed rest which led to a marked decline in their maximal oxygen uptake (VO₂ max) from an average of 3.3 to 2.4 liters per minute, indicating a significant loss in cardiorespiratory fitness. However, an eight-week endurance training program not only restored their VO₂ max levels but improved them beyond baseline, reaching an average of 3.9 liters per minute. This recovery was associated with increases in stroke volume and cardiac output, showcasing the remarkable adaptability of the cardiovascular system when stimulated by consistent physical activity.
The results of this study hint that in addition to our body possessing a cellular memory of resistance training, there might also be some sort of “cardiovascular memory” that helps to kick-start training adaptations following a period of inactivity or detraining in a group of previously fit people.
This idea wasn’t fully investigated by the Dallas Bed Rest Study because the participants didn’t initially undergo a period of exercise training, and the mechanisms governing the overshot in aerobic fitness during retraining weren’t investigated.
According to new research, epigenetics might explain much of the story.
Published in the Journal of Applied Physiology: Cell Physiology,1 the study involved 20 healthy, previously untrained participants (11 men and 9 women), with an average age of around 25. Participants were selected based on specific inclusion criteria, including a VO₂ max below 40 mL/kg/min for women or 45 mL/kg/min for men, and no history of structured training.
The study was divided into three distinct phases: an eight-week training phase, a three-month detraining phase, and another eight-week retraining phase. During the detraining phase, participants were instructed to return to their habitual physical activity without engaging in structured exercise programs.
Participants engaged in three sessions per week of high-intensity interval training (HIIT), totaling 24 sessions per 8-week phase. Each session began with a 10-minute warm-up followed by high-intensity intervals consisting of a mix of short (1–2 minutes) and long (3–4 minutes) durations performed at intensities around 120% of the participants’ baseline maximum power output with rest periods set to allow partial recovery. All sessions were performed on a stationary bike.
During the detraining phase, participants resumed habitual activity levels without structured exercise. Physical activity was monitored using accelerometers to ensure compliance, and this phase allowed sufficient time (twelve weeks) for physiological adaptations to regress. Measurements—including maximal aerobic capacity, power output, changes in DNA methylation, and gene expression—were conducted at baseline, post-training, post-detraining, and post-retraining phases.
Muscle memory at the epigenetic level
During the initial training period, VO₂ max increased by 14% while maximum power output rose by 18%, demonstrating significant improvements after eight weeks of HIIT.
During the three-month detraining phase, both VO₂ max and maximum power output returned to baseline levels; the changes were transient in the absence of continued training.
In the retraining phase, both VO₂ max and maximum power output increased again, with gains similar to those achieved during the first training period (+14% and +13%, respectively). Interestingly, no evidence suggested an enhanced or faster recovery of these physiological markers during retraining. This contrasts the molecular findings described below, which provided a more enduring view of adaptation.
After the initial training phase, approximately 21,605 differentially methylated positions (DMPs) were identified, with 67% hypomethylated and 33% hypermethylated. DMPs are specific locations in the DNA where chemical modifications, called methylation, occur. These modifications influence whether genes are turned “on” or “off.”
Hypomethylation was particularly prominent in promoter regions, likely facilitating increased transcription of genes related to HIIT adaptations. During the detraining phase, the number of DMPs decreased to 3,854, but 87% of the remaining DMPs retained their hypomethylation, particularly in promoter regions (areas that control gene activity).
Even during the detraining phase, a large portion of these hypomethylated sites persisted, suggesting the muscle retained a molecular “memory” of the training. This primed the muscle for quicker and more effective re-adaptation during the retraining phase, as shown by an increase in hypomethylated positions.
In the retraining phase, the number of DMPs rose to 10,396, with hypomethylation becoming even more dominant (93%), particularly in promoter regions, suggesting a molecular "priming" effect from the earlier training—some molecular responses (i.e., hypomethylation) were more prevalent after detraining and retraining than during the initial training phase!
Key genes such as ADAM19, INPP5a, MTHFD1L, CAPN2, and SLC16A3 showed consistent hypomethylation across all phases—training, detraining, and retraining. These genes play critical roles in calcium signaling (important for muscle contraction and fatigue resistance), lactate transport (enhancing metabolic efficiency), and mitochondrial function (supporting energy metabolism). Notably, gene expression for these markers increased significantly after the initial training phase and remained elevated even during detraining, highlighting the persistence of molecular adaptations despite a loss of physiological markers.
This mechanism is significant: It highlights how molecular changes in the DNA can sustain the benefits of training even when physiological markers, like VO₂ max, return to baseline. It also explains why retraining after a period of inactivity can yield quick and robust improvements.
The findings of this study align with broader concepts of muscle memory but reveal some key differences when compared to resistance training. Resistance training studies demonstrate muscle memory through mechanisms focused on structural adaptations like muscle growth and strength. Myonuclear retention—the preservation of nuclei within muscle fibers—plays a pivotal role in resistance training, as these nuclei facilitate quicker muscle regrowth during retraining. Resistance training also induces molecular changes, such as the activation of satellite cells, that support hypertrophy and strength recovery. In other words, you can get bigger and stronger after detraining if your body has previously been exposed to resistance exercise.
In contrast, the molecular memory observed in HIIT primarily targets metabolic efficiency, calcium signaling, and mitochondrial adaptations.
The physiological outcomes also differ. Resistance training has been shown to enable faster recovery of muscle hypertrophy and strength during retraining. In comparison, while HIIT retains molecular priming, it does not lead to accelerated gains in VO₂ max or power output during retraining. Instead, HIIT’s molecular adaptations provide a foundation for consistent performance improvements and efficient retraining after periods of inactivity.
Muscle memory may not extend quite as robustly to the physiological outcomes because the heart, lungs, and blood vessels are much more responsive to detraining than muscle satellite cells and myonuclei. It takes a lot of training to change the structure and function of the heart (but seemingly not a lot of inactivity to make it weaker). I’m a bit surprised that the detraining period didn’t have more of an effect than it did—my hypothesis would have involved aerobic fitness tanking well below baseline after 3 months. However, given the fairly low activity levels of the participants, perhaps the results that were observed should have been expected.
This study can explain two phenomena that you’ve likely experienced.
For one, it makes it apparent why former endurance athletes who quit for a while often can return to the sport with less inertia than those who’ve never competed. Epigenetic changes that occur during training may never disappear—they just go into hibernation.
Second, it explains why you can take a few weeks or even months off of training and eventually (with dedicated training) get back to your former self. You can thank those hypomethylated promoter regions for a smooth return to activity.
Sadly, what doesn’t seem possible is for us to game the system. By this, I mean that we can’t “overtrain” before a long layoff (vacation, holiday, etc.) and expect our body to bounce back more rapidly or gain fitness quicker when we return. The molecular priming effect—at least when studied in the time frame of the current study—doesn’t lend itself to robust physiological “muscle memory.” Would a longer initial training period—or perhaps a lifetime of physical activity—change these results? I think so, but that’s just my speculation.
Just like elephants, our muscles never forget.
Thanks for reading. See you next Friday.
~Brady~
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Perfectly timed article after my unplanned 2 weeks off due to the holiday season.
Would be interesting to see what happens with a combination of training/detraining of both, meaning both muscular and cardiovascular adaptations.