A new study published in GeroScience by Juliette Lancelot of Nantes Université and colleagues set out to answer that question with unusual rigor. The research team compared the behavior of the gastrocnemius medialis muscle–tendon unit in young, physically active adults and in active older adults who were classified as non-frail or pre-frail. Crucially, the investigators matched the two groups on physical activity levels, a design choice that matters enormously. Most previous studies comparing young and old participants did not control for activity, making it impossible to distinguish the effects of aging itself from the effects of simply moving less. By ensuring comparable activity between groups, the French team could isolate what aging, in the presence of habitual exercise, actually does to the muscle–tendon machinery.

The technical execution of the study was demanding. Participants performed eccentric calf exercises under two very different conditions: highly controlled maximal and submaximal contractions on an isokinetic dynamometer, which holds the ankle at a fixed angular velocity while measuring torque, and a simple heel-drop exercise that anyone can perform at home on a step. Throughout each contraction, the researchers used ultrasonography to simultaneously track the length of individual muscle fascicles, the bundles of muscle fibers that run through the gastrocnemius, and the strain of the Achilles tendon, meaning how much the tendon stretched relative to its resting length. At the same time, they recorded ankle joint angle, the torque produced at the ankle, and the electrical activation of the calf muscles using surface electromyography, following established consensus guidelines for electrode placement and force estimation.

This simultaneous imaging and force monitoring allowed the team to examine what biomechanists call muscle–tendon decoupling. During many movements, the tendon stretches and recoils while the muscle fascicles stay nearly isometric, operating close to their optimal length for force production. This division of labor is one of the secrets of efficient human locomotion: the cheap, elastic tendon does much of the mechanical work while the metabolically expensive muscle fine-tunes its position. If aging disrupted this coordination, for example by making the tendon stiffer so that fascicles had to lengthen more, or by altering neural activation patterns, the consequences could ripple through balance, walking economy, and fall risk in older adults, since ankle muscle strength and triceps surae function are known to discriminate fallers from non-fallers.

The results, however, delivered a surprise. Across every condition tested, whether maximal or submaximal effort on the dynamometer, or the practical heel-drop exercise, and across every measured variable, the researchers found no statistically significant differences between the young and older groups. Tendon strain was similar. Fascicle length and fascicle velocity during the lengthening phase were similar. Achilles tendon stiffness, assessed separately, did not differ between the age groups either. Every comparison returned p values above 0.05, the conventional threshold for statistical significance. In other words, the older adults, all of whom maintained substantial habitual physical activity, produced muscle–tendon behavior during eccentric exercise that was essentially indistinguishable from that of their younger counterparts.

The finding challenges a body of earlier work that reported age-related alterations in tendon properties and fascicle–tendon interaction. Previous investigations had documented stiffer Achilles tendons, altered gastrocnemius behavior during walking, and changed fascicle–tendon coordination during hopping and drop jumps in older compared with younger participants. Reviews had also linked age-related changes in Achilles tendon stiffness to modifications in functional activities. But those studies, like much of the aging literature, typically compared sedentary or freely living older adults with young controls, leaving physical activity as an uncontrolled confounder. The new results suggest that many of the so-called aging effects on the muscle–tendon unit may in fact be effects of disuse, and that they are avoidable.

The implications for rehabilitation are potentially significant. Eccentric exercise is prized in geriatric rehabilitation because lengthening contractions generate high force with low energy expenditure, making them tolerable for people with limited cardiovascular capacity, and because they reliably stimulate tendon adaptation. Mechanically, tendons respond to repeated loading by adjusting their material properties and morphology, a plasticity that has been demonstrated in systematic reviews of exercise interventions across the lifespan. If active older adults already exhibit tendon strain, fascicle dynamics, and stiffness comparable to young adults, then eccentric training prescriptions may not need to be fundamentally re-engineered for age. The same loading principles that remodel tendon and muscle in the young appear to remain available to the older neuromuscular system, provided the person has been keeping the machinery in working order.

The study also carries a methodological lesson for the field. By testing both a laboratory dynamometer protocol and a home-based heel-drop exercise, the researchers bridged the gap between controlled biomechanics and real-world training. The heel-drop, in which a person stands on a step, rises onto the balls of the feet, and slowly lowers the heels below the step level, is among the most commonly prescribed eccentric exercises for calf and Achilles rehabilitation. Demonstrating that the underlying muscle–tendon mechanics behave similarly in the laboratory and at home strengthens the ecological validity of the findings and gives clinicians confidence that what is measured on a dynamometer translates to the living room floor. The team’s use of semi-automated ultrasound fascicle tracking software and careful monitoring of muscle activation further guards against the measurement artifacts that have complicated this literature.

There are, of course, boundaries to what the study can claim. The older participants were active and at most pre-frail, so the results speak to successful or well-maintained aging rather than to frail individuals or those with sarcopenia, whose muscle–tendon behavior may still differ. The measurements focused on the gastrocnemius medialis and Achilles tendon during a single class of movements, and other muscle groups or faster, more ballistic tasks could reveal age differences that slow eccentric exercise does not. The authors also note that their findings suggest, rather than prove, that maintaining high physical activity with increasing age mitigates the effects of aging on muscle–tendon behavior and muscle–tendon interactions; a longitudinal study that follows sedentary adults as they adopt or abandon exercise would be needed to establish causation directly.

Even with those caveats, the message is striking and, for an aging global population in which insufficient physical activity remains widespread, quietly urgent. The muscle–tendon unit does not appear to be doomed by the passage of time itself. In people who keep moving, the elastic partnership between calf muscle and Achilles tendon, the elegant decoupling that lets a cheap spring do the work of an expensive engine, persists into older adulthood largely intact. For clinicians designing eccentric rehabilitation protocols, the findings suggest that age alone should not dictate a fundamentally different mechanical approach. And for everyone else, the study adds to a growing case that the neuromuscular consequences we often blame on aging are, to a meaningful degree, negotiable, and that the currency for negotiating them is simply sustained, habitual movement.

Subject of Research: Age-related differences in gastrocnemius medialis muscle–tendon behavior during eccentric exercise in physically active young and older adults

Article Title: Gastrocnemius medialis muscle–tendon behavior during eccentric exercise in young and active older adults

Article References: Lancelot, J., Souron, R., Chapelet, G., Boureau, A.-S., Demoy, E., Rampal, M., Piriou, M., Cornu, C., & Crouzier, M. (2026). Gastrocnemius medialis muscle–tendon behavior during eccentric exercise in young and active older adults. GeroScience. https://doi.org/10.1007/s11357-026-02547-7

Image Credits: AI Generated

DOI: 10.1007/s11357-026-02547-7

Keywords: eccentric exercise, muscle–tendon unit, Achilles tendon, gastrocnemius medialis, aging, ultrasound imaging, tendon stiffness, fascicle dynamics, muscle–tendon decoupling, rehabilitation, older adults, GeroScience

Eccentric exercise occurs when a muscle lengthens under load, as it does when lowering a weight or running downhill, generating high mechanical tension at a comparatively low metabolic cost. Concentric exercise, by contrast, shortens the muscle under load, as in uphill running or lifting. Physiotherapists and sports physicians have long observed that eccentric training builds strength efficiently and reduces the incidence of hamstring injuries by as much as 56.8 to 70 percent in some reported cohorts, yet the underlying mechanism linking this unique stress profile to enhanced tissue repair has remained elusive. The new research, conducted in mice using a barium chloride-induced injury model that reproducibly triggers myofibre necrosis while preserving the satellite cell niche, set out to close that gap.

The team subjected injured mice to five days of treadmill running, with one group performing downhill running at a minus 15-degree incline to simulate eccentric exercise and another performing uphill running at plus 15 degrees to simulate concentric exercise. Seven days after injury, the downhill-running animals displayed markedly better organised regenerating tissue in the tibialis anterior muscle, less collagen Iα deposition, and elevated expression of the myogenic regulators Myod, Myog and embryonic myosin heavy chain. Immunofluorescence revealed more newly formed eMyhc-positive fibres, and the extensor digitorum longus muscles of the eccentric group generated greater maximal tetanic force. In short, eccentric contraction was the more effective healer.

To explain the difference, the researchers turned to extracellular vesicles, nanoscale particles typically ranging from roughly 50 to 150 nanometres that cells release to ferry proteins, lipids, RNAs and metabolites between cells. Skeletal muscle is known to shed these vesicles during exercise, and the team hypothesised that the two contraction modes might load them differently. Western blotting showed that Rab27a, a key regulator of vesicle secretion, was more strongly expressed after eccentric exercise, and ex vivo experiments using the Aurora Scientific 1200A system confirmed that isolated soleus, extensor digitorum longus and tibialis anterior muscles secreted more vesicles during eccentric than concentric contractions. Transmission electron microscopy and nanoparticle tracking analysis characterised the vesicles, while canonical markers such as CD63, ALIX, TSG101 and CD9 were elevated in the eccentric group.

The causal evidence was compelling. When the researchers blocked vesicle production with GW4869, an inhibitor of vesicle biogenesis, the benefits of eccentric exercise largely vanished: regenerating muscles showed disorganised morphology, increased fibrosis, reduced myogenic marker expression and fewer newborn fibres. Conversely, when vesicles harvested from the muscles of exercised mice were injected directly into injured muscles, the vesicles entered satellite cells, as demonstrated by PKH26 labelling, and accelerated repair. Critically, vesicles from eccentrically exercised donors outperformed those from concentric donors and sedentary controls, producing better tissue architecture, less collagen deposition, higher Myog protein and more eMyhc-positive regenerating fibres.

What made the eccentric vesicles so potent? The answer appears to lie in their cargo. Non-targeted metabolomic profiling using liquid chromatography-mass spectrometry revealed that lipid metabolites, particularly phosphatidylcholines and sphingomyelins, were the most enriched class of upregulated molecules in vesicles from eccentrically exercised muscle. Quantitative PCR showed corresponding upregulation of lipid metabolism genes, and KEGG pathway analysis confirmed that lipid metabolism was significantly more active in the eccentric vesicles. Because phosphatidylcholines supply substrates for membrane remodelling, a process essential for myoblast fusion and fibre growth, while sphingomyelins populate lipid rafts that organise pro-differentiation signalling, the authors propose that these lipids act as both building blocks and signals for regeneration.

Functional tests strengthened the case. When the researchers blocked lipid metabolism in exercising muscle using BMS-309403, an inhibitor of the fatty acid binding protein AP2, vesicles extracted from those muscles lost nearly all of their regenerative advantage, both in injured mice and in cultures of C2C12 myoblasts. Supplementation experiments with PI (18:1/18:1), a phosphatidylinositol species highly enriched in eccentric vesicles, activated the energy-sensing AMPK pathway, boosted MyoD expression and rescued the pro-myogenic capacity of otherwise weaker vesicle preparations, while the AMPK inhibitor Compound C attenuated these effects. Vesicles from eccentric exercise also raised ATP levels and mitochondrial membrane potential in recipient cells.

Transcriptomics added a further layer of mechanism. RNA sequencing of myoblasts treated with the different vesicle populations showed activation of fatty acid metabolism pathways and a stepwise, exercise-dependent increase in nine genes, including Prkag3, a known supporter of muscle repair, and the mitochondrial energy-sensing genes Cox7a1, Cox6a2 and Cox8b. Together with the metabolomic and pharmacological data, the picture that emerges is of vesicles acting as lipid-rich metabolic packages that reprogramme satellite cells and myoblasts toward an energetically primed, differentiation-ready state, thereby accelerating the reconstruction of damaged tissue.

The therapeutic implications are considerable, particularly for patients who cannot exercise after injury. Because improper eccentric training can itself cause secondary muscle damage, the prospect of isolating or mimicking the vesicles released during downhill running, and administering them exogenously, offers a way to capture the regenerative benefits of exercise without the movement that injured limbs may not tolerate. The authors caution that significant hurdles remain before clinical translation, including scalable production with consistent quality, batch-to-batch variability, maintaining vesicle stability during storage, achieving targeted delivery to injured muscle, and excluding immunogenicity or long-term adverse effects. The study also used only male mice, leaving open whether the findings extend to females, and other exercise-induced factors beyond vesicles may contribute to regeneration. Nevertheless, by demonstrating that the healing power of eccentric contraction travels, at least in part, inside lipid-laden extracellular vesicles, the work transforms these nanoscale particles from a curiosity of intercellular communication into a promising natural therapeutic candidate, one that could eventually shorten recovery times for athletes and patients alike and reshape rehabilitation medicine around the molecular conversation that exercising muscles hold with their own stem cells.

Subject of Research: Muscle-derived extracellular vesicles released during eccentric exercise that promote skeletal muscle regeneration after injury

Article Title: Skeletal Muscle–Derived Extracellular Vesicles During Eccentric and Concentric Exercise Promote Muscle Regeneration After Injury

Article References: Zhou, Y., Shao, X., Zhang, P., Lin, J., Chen, X., An, X., Jiang, Z., Wang, H., Fang, D., Xian, Y., Liu, B., Shen, T., Chen, Y., Li, K., Liu, H., Li, Y., Jiang, Q., & Guo, B. (2026). Skeletal Muscle–Derived Extracellular Vesicles During Eccentric and Concentric Exercise Promote Muscle Regeneration After Injury. Journal of Cachexia, Sarcopenia and Muscle, 17(5), Article e70374. https://doi.org/10.1002/jcsm.70374

Image Credits: AI Generated

DOI: 10.1002/jcsm.70374

Keywords: extracellular vesicles, eccentric exercise, concentric exercise, skeletal muscle regeneration, satellite cells, lipid metabolites, myokines, muscle injury, metabolomics, AMPK signalling, myoblast differentiation, rehabilitation