For older patients, memory is a factor that extends beyond the brain.

New research finds that muscles remember periods of disuse, and the consequences appear quite different in young vs old muscle. The findings could help explain why returning to activity after an injury or illness is more of a slog for older patients than a bounce-back. 

“A lot of folks are experiencing events that tip them over frailty in their 50s,” said Stuart Phillips, PhD, professor of kinesiology at McMaster University in Hamilton, Ontario, Canada. 

A “disuse event” — the type of injury or illness that drastically curtails your physical activity and leaves you with smaller, weaker muscles — creates molecular markers that influence how your muscle cells will respond to a future muscle-shrinking event. 

That’s according to a new study from molecular physiologist Adam Sharples, PhD, and his research team at the Norwegian School of Sport Sciences in Oslo, Norway.

The study builds on prior research from Sharples and others that shows muscles remember being bigger and stronger, making it easier to regain those qualities than it was to build them in the first place. In 2018, Sharples’s group provided the first evidence of human muscle retaining an epigenetic memory of growth. That is, within the DNA, there are molecular changes reflecting a history of previous development — what Sharples calls “positive” muscle memory. Now the researchers are investigating how muscles retain “negative” memories, as well.

What the Research Shows

In the new study, 10 young participants (mean age, 26.5 years) twice had their nondominant leg immobilized in a brace for 2 weeks, with 7 weeks in between to regain the muscle they’d lost.

Both times, muscle loss was about the same (just over 3%) — but during the second bout, there was less DNA methylation. “The genes that were shut down after the first period of wasting were shut down less the second time around,” Sharples said. In the young muscle, “it seems they were being protected.”

To assess how this mechanism fares with age, researchers tested aged rats. Ethical concerns prevented imposing repeated immobilization on older humans, given the difficulty they would have regaining strength and function.

Unlike the young participants, the older rats lost more lean mass during the second period of disuse. Crucially, gene networks associated with aerobic metabolism showed increased methylation — suggesting that while young DNA adapts to protect those pathways, older DNA may undergo a maladaptive shift that could compromise recovery.

Give Muscles Something to Remember

Phillips, director of McMaster’s Physical Activity Centre of Excellence and a prolific resistance training researcher, bridges the gap between the lab and the clinic. While Sharples documents the molecular mechanisms of muscle memory, Phillips studies and treats its effects in patients recovering from injury, surgery, and chronic illness.

He’s seen collegiate athletes who “made some insane gains” as well as older adults struggling to recover. “There’s a rapid deconditioning with age,” Phillips said. “Their muscle mass takes much longer to come back.” In a 2018 study, Phillips and his team had older participants (average age: 69) reduce their average daily step count by more than 80%. After two weeks, they saw a significant drop in muscle protein synthesis – one that still hadn’t returned to baseline after two weeks of resumed normal activity.

The solution, Phillips said, is to start preparing now. “Build yourself up, and then work like hell to hang onto it.” Encourage patients to build a buffer of muscle mass to guard against frailty later. The less muscle you have at the time of a disuse event, and the less active you are in general, the worse that wakeup call will be.

For patients currently recovering from illness or surgery, keep in mind that the body they have now is not the body they had before, said both Phillips and Sharples. Balance the message of “do less and recover” with an intentional mindset around “making a conscious effort to do more after you’re mainly pain-free,” Sharples said.

Because no matter how much one would like to forget the event, muscles remember.