Why Do Some Older Adults Build More Muscle Than Others?
A look inside muscle metabolomic markers of hypertrophy.
Some older adults build far more muscle from weight training than others, even on the same program. A new study published in GeroScience looked at why, and found the answer may lie in the chemistry happening inside the muscle itself.
Researchers from the University of São Paulo and the University of Liverpool took muscle biopsies from 67 healthy older adults before and after 10 weeks of resistance training, then compared the metabolic profiles of those who gained the most muscle against those who gained the least. What they found points to amino acid metabolism, particularly tryptophan, and mitochondrial energy production as key factors that separate big responders from small ones.
Aim
The study set out to identify whether distinct metabolic profiles in skeletal muscle could explain why some older adults respond far better to resistance training than others. Researchers specifically examined the upper and lower tertiles of hypertrophic response to see if their muscle chemistry looked different after the same training program.
Methods
67 healthy older adults (average age 68) completed 10 weeks of supervised resistance training, three days per week, using unilateral knee extensions. All participants consumed 20g of whey protein twice daily throughout the intervention.
Quadriceps muscle size was measured by MRI before and after training. Muscle biopsies were taken from the vastus lateralis before and 48 hours after the final training session. Participants were split into two groups based on how much their muscle cross-sectional area (CSA) changed:
UPPER group: grew more than 7.7% in CSA
LOWER group: grew less than 5.6% in CSA
25 participants in each group; the middle tertile was excluded from analysis
Muscle samples were analysed using untargeted liquid chromatography-mass spectrometry (LC-MS), mapping over 2,500 metabolites across 104 metabolic pathways.
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Results
Both groups built muscle. The LOWER group gained 3.3% in quadriceps CSA, while the UPPER group gained 10.3%, a roughly three-fold difference. The groups were matched at baseline for age, body mass, BMI, strength, and clinical conditions, meaning the difference in response was not explained by who they were going in.
The metabolomics analysis correctly classified UPPER vs. LOWER responders with about 75% accuracy using polar metabolite profiles. Pathway enrichment analysis revealed several key differences in the UPPER group compared with the LOWER group:
Tryptophan metabolism was the most significantly enriched pathway. The UPPER group showed higher levels of tryptophan, kynurenine, kynurenic acid, indole derivatives, and serotonin (5-HT). Kynurenic acid and NAD+ have been linked to improved respiratory fitness and oxidative capacity in muscle.
Branched-chain amino acids (BCAAs) — leucine, valine, and isoleucine — were elevated in UPPER. Importantly, BCAA breakdown products (catabolites) were not detected, which the researchers suggest may reflect more efficient BCAA utilisation rather than excessive breakdown.
TCA cycle intermediates such as citrate, glutamic acid, glutamine, proline, and arginine were higher in UPPER, indicating more active mitochondrial energy production.
Carnosine and acylcarnitines were elevated in UPPER, pointing to better capacity for pH buffering, ATP regeneration, and fatty acid transport into the mitochondria.
Energy-related metabolites, including adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were also increased in the UPPER group, consistent with greater energy turnover.
