Before Adam Sharples became a molecular physiologist studying muscle memory, he played professional rugby. Over his years as an athlete, he noticed that he and his teammates seemed to return to form after the offseason, or even from an injury, faster than expected. Rebuilding muscle mass and strength came easy: It was as if their muscles remembered what to do.<\/p>\n
In 2018, Sharples and his research lab, now at the Norwegian School of Sport Sciences in Oslo, were the first to show<\/a> that exercise could change how our muscle-building genes work over the long term. The genes themselves don\u2019t change, but repeated periods of exertion turns certain genes on, spurring cells to build muscle mass more quickly than before. These epigenetic changes have a lasting effect: Your muscles remember these periods of strength and respond favorably in the future.<\/p>\n Intuitively, this makes sense. Past exercise primes your muscles to respond more robustly to more exercise. Over the past few years, Sharples\u2019s lab has found that muscles have additional molecular mechanisms for remembering exercise; he and other scientists have been building on this research, too, confirming epigenetic muscle memory in young and aged human muscle<\/a>, after different modes of training<\/a>, as well as in mice<\/a>. Now 40 years old, Sharples is still thinking about how our muscles remember but has lately been investigating the inverse trajectory: Do muscles have a similar memory for weakness?<\/p>\n The answer appears to be yes. \u201cOur new data shows that muscle does not just remember growth\u2014it also remembers wasting,\u201d Sharples told me, of a study<\/a> published in preprint on bioRxiv and currently in peer review for Advanced Science<\/a>. \u201cThe more encounters you have with injury and illness, the more susceptible your muscle is to further atrophy. And, well\u2014that\u2019s what aging is, isn\u2019t it?\u201d<\/p>\n The Norwegian government\u2019s research council has been funding Sharples\u2019s research and has a vested interest in the lab\u2019s discoveries. In the next decade, Norway is expected to become a \u201csuper-aged society<\/a>,\u201d in which more than one in five people are age 65 or older. Japan and Germany<\/a> have already crossed this threshold, and the United States is expected to reach it by 2030<\/a>. Age-related muscle weakness is a major factor in falling risk; falling is a leading cause worldwide of injury and death<\/a> in people 65 and older. Better understanding how muscles remember and react to their weakest moments is a crucial step toward knowing what to do about it.<\/p>\n As part of the new study, Sharples\u2019s team studied repeated periods of atrophy in young human muscle, using a knee brace and crutches to immobilize participants\u2019 legs for two weeks at a time. This level of disuse, Sharples said, is comparable to real-world situations in which muscle rapidly loses size and function\u2014limb immobilization after fractures or other injuries, periods of hospitalization or bed rest, reduced weight-bearing during recovery. A couple of years ago, I went to observe this research for my book On Muscle<\/a>; one study participant, an avid skier and cyclist, told me he was shocked by how significantly the muscles in his leg deteriorated after just a couple of weeks of immobilization. The team also ran a concurrent study in aged rat muscle, in collaboration with Liverpool John Moores University; in both studies, repeated periods of disuse led to epigenetic changes\u2014shifts in the way genes were expressed.<\/p>\n These changes affected the core functions of muscle cells, hampering the genes in mitochondria\u2014the powerhouses of the cell, which generate the energy required to contract and relax muscle fibers. Letting muscles weaken suppressed genes involved in mitochondrial function and energy production in particular, including genes that are essential for muscle endurance and recovery. The researchers also found that a key marker of mitochondrial abundance dropped more drastically after repeated atrophy than after the first episode, indicating that repeated disuse makes muscle more vulnerable. In other words, the evidence suggests that every time you fall down the hole, it becomes more difficult to climb back out.<\/p>\n Similar changes occurred in both the young human muscle and the aged rat muscle. But the young muscle could adapt and recover. After repeated atrophy, it showed a less exaggerated gene-expression response than the aged muscle did. \u201cThere seems to be some resilience and protection with young muscle the second time around,\u201d Sharples said. He likened this to an immune-system response: Young muscle responds better to atrophy the second time because it has encountered it before and knows how to bounce back. By contrast, aged muscle becomes more sensitive after repeated atrophy, showing a worsened response with the second episode.<\/p>\n