In 81 healthy men aged 18 to 80, free testosterone fell with age, as did muscle mass and leg press strength. Yet neither free nor total testosterone predicted muscle mass or strength. Free testosterone, but not total, correlated strongly with the vastus lateralis transcriptome. In cultured primary myocytes, testosterone raised androgen receptor abundance and nuclear localisation and enriched protein translation pathways. The authors conclude that testosterone is molecularly active in adult muscle, but those effects do not translate into measurable differences in size or force.
This cross-sectional result complicates a popular assumption: that age-related testosterone decline drives sarcopenia, and that restoring levels should restore muscle. Here, men with higher free testosterone were no stronger or more muscular than peers at the same age, which fits with randomised trials where testosterone therapy in older men produces modest lean mass gains but inconsistent functional benefit, and where resistance training remains the stronger lever. The pubertal-programming interpretation is plausible but untested by this design. Limits are real: 81 participants, one muscle, a strength estimate rather than a measured one-rep max, and correlation without causation. The cell experiments used only 5 young and 7 older donors, and molecular enrichment in a dish does not prove functional gain in a body. This is a preprint, not yet peer-reviewed, so conclusions may shift. For readers, the practical takeaway is cautionary: a low-normal testosterone reading is a weak explanation for lost muscle in healthy men, and training and protein intake likely matter more. Incremental and mostly confirmatory, though the free-versus-total transcriptome signal is a useful detail.