When the tobacco hornworm has nearly completed its 18-day metamorphosis, it uses a set of powerful abdominal muscles to escape from the confines of its old exoskeleton. In its new life as a tobacco hawkmoth, it doesn’t need those oversized abs anymore—so they shrink. Over the course of just three days, the muscles get 40 percent smaller, a loss that’s equivalent in human terms to an 80-year-old after three decades of the muscle-wasting condition sarcopenia. But there’s something curious about this shrinkage: as the muscle cells die, all of the cell nuclei inside live on.
According to a new article in Frontiers in Physiology by University of Massachusetts, Amherst biologist Lawrence Schwartz, the hawkmoth’s metamorphosis tells us something important about the human phenomenon of muscle memory. If you achieve a certain level of fitness and then lose it, it’s easier to regain that fitness than it was to get there for the first time. This is conventional wisdom in both strength and endurance training, and there are undoubtedly many factors—psychological and practical as well as physiological—that contribute to it. But in recent years, there has been growing evidence that your muscle cell nuclei play a key role.
Muscle cells are very unusual in that they can have more than one nucleus per cell. In fact, they can have hundreds of nuclei in a single cell. That’s because they can be enormous: a single muscle fiber from the sartorius can be 23 inches long. In order to synthesize enough muscle proteins to keep this fiber intact, you need more than one nucleus. A theory called the “myonuclear domain hypothesis” suggests that each nucleus can only support a given cell volume, so as muscle cells get bigger—because you’re hitting the gym, say—your muscle cells add a proportionate number of additional nuclei.
The big question is what happens when you slack off from the gym. Scientists initially thought that the number of nuclei would decrease as your muscle cells shrink, and there was some evidence that seemed to suggest that nuclei were indeed succumbing to “programmed cell death” as muscles atrophied. But a series of careful mouse experiments a decade ago by Norwegian physiologist Kristian Gundersen contradicted this idea: when mice stopped exercising, their muscle shrank by as much as 50 percent, but the number of nuclei stayed exactly the same.
This observation suggested a mechanism for the anecdotal idea of muscle memory: if you get fit then unfit, you’ll still have all the extra nuclei hanging around in your muscles, making it easier for them to grow when you start exercising again. In one of Gundersen’s experiments, mice who had previously been strong (and thus had more dormant nuclei) gained 36 percent in muscle size during an exercise program, while other mice doing the same program for the first time only gained 6 percent.
One of the challenges in trying to figure out what happens to your muscles when you stop exercising is that various other types of cells are mixed in with your muscle fibers in any given muscle. That’s why scientists initially thought the nuclei were destroyed as muscles shrank: their tests showed indirect evidence of defunct nuclei that, it turns out, were probably from other cells. Schwartz’s moth data helps clear that confusion up, since the moth muscles are almost exclusively composed of muscle fibers.
Another research group, at Temple University, also published some intriguing data in rats last fall. While most of the muscle memory research focuses on muscle size, the Temple team looked at the mitochondria within the muscles—the “powerhouses” that generate the fuel for sustained exercise.
The most significant adaptation to endurance training is an increase in the amount of mitochondria in your cells. When you stop training, the amount of mitochondria declines again. But the extra nuclei, which stick around, contain the genetic information that controls the formation of new mitochondria. As a result, the Temple researchers demonstrated that when you start training again, your cells are already primed to ramp up mitochondria production more rapidly if you’ve been fit before.
One frequently discussed implication of this muscle memory research is that athletes who dope gain an advantage that lasts far longer than the typical four-year ban, and possibly for the rest of their careers—if not longer. When I wrote about this topic a few years ago, Gundersen told me that the existing evidence suggests that human muscle cell nuclei can persist for decades. His estimate: “It’s possible that they are more or less permanent once they are formed.”
There’s also a public health angle, Schwartz points out: “During adolescence, muscle growth is enhanced by hormones, nutrition, and a robust pool of stem cells, making it an ideal period for individuals to ‘bank’ [muscle nuclei] that could be drawn upon to remain active in old age.” That ship sailed long ago for me, but the implications are still relevant. Even if putting on muscle and gaining fitness isn’t as easy for me now as it was 20 years ago, it’s still possible, and it’s easier than it will be in another 20 years. If I don’t want to end up as the human version of that withered hawkmoth, now’s the time to hit the gym and bank some nuclei.
My new book, Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance, with a foreword by Malcolm Gladwell, is now available. For more, join me on Twitter and Facebook, and sign up for the Sweat Science email newsletter.