Researchers at Simon Fraser University built a detailed computer simulation of how a protein meal switches on muscle-building in human skeletal muscle, then used it to interrogate why older adults build less muscle after eating (a phenomenon called anabolic resistance). When they fed the model each of the individually proposed causes of ageing muscle loss one at a time, no single defect could reproduce the blunted response seen in real older adults. Only when several dysfunctions were stacked together did the simulation match the older-adult data. The same logic applied to treatment: fixing any one target failed, and restoring muscle-building required hitting several targets at once. The headline message is that age-related muscle loss is a multifactorial problem that will likely resist single-ingredient solutions.
Sarcopenia, the slow erosion of muscle mass and strength with age, is driven largely by anabolic resistance: older muscle responds weakly to the signals in a protein meal that normally tell it to build. For two decades, researchers have catalogued suspects. Amino acids get skimmed off by the gut and liver before reaching muscle. Transport of amino acids into muscle slows. Insulin signalling weakens. The core growth switches mTOR and p70S6K become less abundant and less sensitive. Each suspect had evidence, but none had ever been shown to be the culprit on its own.
Testing these interacting failures in living people is close to impossible, so the team took a systems-biology approach. They adapted a validated kinetic model of leucine signalling, leucine being the amino acid that most strongly flips the mTOR switch, and ran virtual feeding experiments across thousands of simulated individuals. They classified each virtual person as anabolic sensitive or anabolic resistant using thresholds anchored to real human feeding studies.
The central finding is one of emergence. When the model applied any single age-related defect using realistic, literature-derived magnitudes, muscle protein synthesis barely budged. The blunted response characteristic of ageing appeared only when multiple defects operated together. In other words, anabolic resistance is not one broken part but a network effect.
A second finding is more surprising. Older muscle appears to run a compensatory program, keeping its growth machinery partly switched on even at rest. In the simulation this compensation propped up baseline muscle-building, but at a cost: it used up the muscle’s reserve capacity, leaving less room to respond to a meal.
The therapeutic implications are sobering. Single-target interventions, the model’s stand-ins for a drug or supplement aimed at one pathway, consistently failed to restore a youthful response once several defects coexisted. Only coordinated, multi-target strategies recovered muscle-building. The authors are careful: this is a simulation calibrated on young-adult and male data, so its predictions are hypotheses for experiments, not clinical advice. But it offers a clear map of which combinations of failures matter most, and a warning that the search for a single anti-sarcopenia pill may be looking for something that cannot exist.
Actionable Insights
Read this as a map of the problem, not a prescription. The study tested no supplement or drug in people; it is a simulation. With that caveat, several practical points hold up.
First, the size of the problem is large. Older adults in the anchoring human studies incorporated about 0.27 g of leucine into muscle from a standard 15 g essential amino acid meal, versus about 0.46 g in young adults. That is roughly a 41 percent drop. Expressed as a standardized effect size, Cohen’s d is about 1.9. Cohen’s d simply asks how far apart two groups are relative to their natural spread; anything above 0.8 is considered large, so 1.9 is very large. This is a real, substantial gap, not a statistical technicality.
Second, the per-meal loss looks small but compounds. The model put the postprandial deficit at about 42 mg of leucine per meal. Trivial once, but repeated across every meal for years it tracks with the slow pace of real muscle loss.
Third, do not expect one lever to fix it. The simulation repeatedly showed that single fixes fail when several defects coexist. Practically, that supports a stacked strategy: adequate per-meal protein with enough leucine, plus resistance exercise, which the paper notes restores the muscle’s sensitivity to feeding. No single item substitutes for the others.
Context and Source
- Open Access Paper: Multifactorial nature of anabolic resistance in ageing skeletal muscle: A systems modelling study.
- Authors and institutions: Taylor J. McColl, Daniel R. Moore, Eldon Emberly, David D. Church and David C. Clarke. Lead institution Simon Fraser University, Burnaby, British Columbia, Canada, with the University of Toronto (Canada) and the Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences (USA).
- Journal: The Journal of Physiology, 2026, volume 604.\
- Impact evaluation: The impact score of this journal is 4.7 (Journal Impact Factor), evaluated against a typical high-end range of 0 to 60+ for top general science, therefore this is a Low to Medium impact journal on that absolute scale. That framing understates its standing within its own field: with a CiteScore near 8.9 it sits in the top quartile (Q1) of physiology journals and is one of the oldest flagship specialist titles in the discipline. So read the number as Low to Medium in absolute terms but High for a subject-specific physiology journal.