Previous studies have indicated that after resistance training and subsequent refrainment for varying time periods, we regain muscle force and mass more quickly in response to training compared to how long it took intially. In fact, after discontinuing training for up to 2 years in one study, muscles remained at a greater hypertrophic status and retained a greater force compared to their untrained levels. This phenomenon of “muscle memory” is often suggested to be from neural adaptations to exercise, but this cannot explain the hypertrophic differences after disuse. A new study suggests that the nuclei in muscle cells may be the major memory mechanism and explain these findings.
Because muscle cells are so large, they require multiple nuclei. Nuclei are likely increased in number by mitosis and fusion of muscle stem cells to muscle fibers in response to resistance, but previously thought that they are removed by apoptosis during muscle disuse, when they atrophy. Bruusgaard et al. explored this issue in their study.
In the first experiments, the Extensor digitorum longus muscle were hypertrophied in Wistar rats by partially removing the major synergist (which overloaded the muscle under study), and nuclei of muscle cells were measured by injection of labeled nucleotides. 21 days later, the cell cross-sectional areas were increased 35%, preceded by an increase in myonuclei number at 54%.
Subsequently, another group of rats underwent the muscle hypertrophy procedure for 14 days, resulting in an increase in cross-sectional area by 35% and myonuclei number by 37%. Some of these animals were denervated at the muscle so that it was not used and atrophied. The cross-sectional area decreased by 60% of the highest value of the other animals, but the number of myonuclei were not reduced to a statistically significant value. Muscles that were only synergist-ablated (but not denervated) had similar nonsignificant changes.
A 3rd group of experiments were done ex vivo, as denervation prevented intracellular injections. Again, muscle was hypertrophied for 14 days, then denervated for 3 months. Cross-sectional area and nuclei number were again increased after the 14 days, and the nuclei number was not significantly different after the 3 month denervation period. The cross-sectional area decreased 23% in that time.
Since previous research has suggested that nuclei that are created when muscle hypertrophy are more prone to apoptosis. The authors here explored this with strict criteria (previously nuclei types were apparently not clearly identified) and found that actually both old and newly created myonuclei are not lost by apoptosis when muscles are not used- in fact they found only 1 of 15,000 (0.007%) screened after 7 and 14 days of denervation that was apoptotic. Extrapolating these results with an equation (because apoptosis cannot yet be monitored as it progresses in each nuclei) yields about 1% of the nuclei lost after 14 days.
The authors also did an experiment which focused on type IIb muscle fibers to test if previously hypertrophied muscles were more resistant to disuse, and subsequent weight on the muscle could result in a more efficient hypertrophic response. A 16% increase in cross-sectional area and 30% increase in myonuclear number was evident after 14 days of overload. They then denervated all muscles and discovered that after 2 weeks, both muscle groups (previously overloaded and non-overloaded) atrophied, but the previously overloaded muscles were 33% larger than those that were not.
As the authors describe, they found that nuclei number increases before muscle fibers hypertrophy, which suggests that more nuclei increases the total protein synthesis capacity of the cells.
The previous paradigm is that nuclei added after resistance are lost during atrophy is not supported, and the authors offer the following model instead:
More nuclei may allow for the protein synthetic capacity needed for larger muscle fibers, and after atrophy, because nuclei number is still elevated, a lessened increase in protein synthesis would be needed by each individual nuclei. This is a more efficient model than creating new nuclei each time resistance triggers hypertrophy then the muscle atrophies.
The authors suggest that this could have implications for older populations whose muscles do not respond as well to resistance training. Satellite cell activation and myonuclei number may be diminished in the elderly. They propose that it may be necessary to increase nuclei number before late in life.
They also cite a couple studies that show that the administration of anabolic steroids increases nuclei number, suggesting performance gains from steroid use may not be transient. If these findings are replicated, even limited use of steroids may bring about long term benefits- should this bring about changes in consequences to use?
Importantly, this study shows that increasing the nuclei number seems to be a main cause of hypertrophy.
Note: the figures and photos are great in this paper, which is open access here.
Bruusgaard JC, Johansen IB, Egner IM, Rana ZA, & Gundersen K (2010). Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proceedings of the National Academy of Sciences of the United States of America PMID: 20713720