New research suggests muscles remember past inactivity at the molecular level.
Muscle loss, or atrophy, caused by inactivity can begin surprisingly fast — even after just days of bed rest, injury, or reduced movement.
For older adults especially, these periods of inactivity can trigger a downward spiral of weakness, slower recovery, loss of independence, and increased risk of future falls and hospitalization.
Scientists have long known that muscles shrink when they are not used, but a major question has remained unanswered: does muscle “remember” past episodes of inactivity?
A new study published in Advanced Science suggests the answer is yes.
Researchers discovered that skeletal muscle stores a kind of “molecular memory” of repeated disuse, and that this memory behaves very differently in young and old muscle. The findings could help explain why younger people often recover strength more easily, while aging muscles become increasingly vulnerable over time.
Young muscle shows resilience
To compare age-related responses, researchers studied repeated lower limb immobilization in young adults alongside an aged rat model. In young adults, each period of disuse caused a similar amount of muscle loss. At the molecular level, however, the second episode triggered signs of protection.
Gene pathways linked to oxidative stress and mitochondria were less disrupted the second time, suggesting that young muscles became more resilient.
Aging changes the memory
Older muscles responded in the opposite way. Repeated inactivity led to more severe atrophy, stronger suppression of genes involved in aerobic metabolism and mitochondrial function, activation of DNA damage pathways, and other changes. Across both humans and animals, repeated disuse produced shared changes in metabolic gene networks, showing that muscle can carry long-lasting molecular traces of wasting.
Taken together, the results suggest that repeated inactivity leaves a molecular imprint on muscle. In young muscle, that imprint may support recovery, while in aged muscle, it can increase vulnerability to further wasting.
Recovery may depend on history
“Muscle carries a history of both strength and weakness, and these molecular memories may accumulate over time to shape how it responds when inactivity occurs again. Understanding how muscles record these past experiences of use and disuse is essential for designing better strategies to support recovery after illness, injury, or age-related decline,” said co-corresponding author Adam P. Sharples, PhD, a professor at the Norwegian School of Sport Sciences, Olso.
“This knowledge will help us determine not only when we should retrain, but also which type and intensity of exercise may be most effective. Our laboratory is now working with the Novo Nordisk Foundation to determine which exercise modes best evoke beneficial memory signals in the muscle’s energy-producing mitochondria, particularly in aging muscle.”
Reference: “Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle” by Daniel C. Turner, Truls Raastad, Max Ullrich, Stian F. Christiansen, Hazel Sutherland, James Boot, Eva Wozniak, Charles Mein, Emilie Dalbram, Jonas T. Treebak, Daniel J. Owens, David C. Hughes, Sue C. Bodine, Jonathan C. Jarvis and Adam P. Sharples, 25 February 2026, Advanced Science.
DOI: 10.1002/advs.202522726
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.