Why an injury often takes longer to heal at 45 than at 25: the Achilles tendon core barely renews after age 17, while aging delays muscle stem cell activation and weakens the brain’s pain inhibition, according to Avi Roy

Why an injury often takes longer to heal at 45 than at 25: the Achilles tendon core barely renews after age 17, while aging delays muscle stem cell activation and weakens the brain’s pain inhibition, according to Avi Roy

On November 2, biomedical researcher Avi Roy posted a thread on X arguing that tendons can adapt to training.

Tendons heal poorly, and estimates of the time needed to replace half their protein range from two months to 200 years. Researchers in Copenhagen used carbon-14 to date the tendon core. Nuclear tests in 1955–1963 nearly doubled its atmospheric abundance, which then declined after the tests were banned. Atmospheric carbon enters proteins through food, leaving a signature of the year in which a protein was made. In most of the 28 samples of Achilles tendon core, this signature dated back many years. Muscle samples from four donors had a recent signature, indicating ongoing renewal. The authors write:

Carbon-14 concentrations in the tendon roughly matched atmospheric levels during the first 17 years of life, suggesting that the tendon core forms as the body grows in height and undergoes almost no renewal thereafter.

The authors consider this a likely explanation for poor tendon healing. The two-month estimate came from experiments using labeled amino acids, which measured collagen synthesis at about 1% per day. The label also enters protein that, the authors suggest, may break down before being incorporated into fibers, making renewal appear faster. In his notes, Roy reconciles the two findings:

Cells continue to produce some collagen, which is what labeling experiments measure. Bomb-pulse radiocarbon data show that the load-bearing core is not replaced. Both findings hold.

Radiocarbon dating showed that collagen in knee cartilage formed during the school years. Estimates based on a chemical marker of protein age put the time needed to replace half the collagen in an intervertebral disc at 95 years in people aged 20–40 and 215 years in those aged 50–80. In both a 25-year-old and a 45-year-old, the tendon core was built during youth. Age-related differences are therefore apparent in the disc, muscle, and brain.

Muscle repair depends on satellite cells, the muscle’s stem cells. After a single resistance training session, satellite cell numbers in fast-twitch fibers rose above baseline after 48 hours in 22-year-old men and after 72 hours in 73-year-old men. Following two weeks of leg immobilization and four weeks of training, men aged 61–74 regained leg strength, but their muscle fiber cross-sectional area and satellite cell numbers did not increase. Both increased in men aged 21–30.

Roy points to weakening pain inhibition as another explanation: pain in one part of the body can prompt the brain to dampen pain elsewhere. In a study in Hamburg, researchers applied heat to the forearms of 64 healthy volunteers and asked them to rate the pain from 0 to 100. Placing a foot in ice water reduced the rating by 9,9 points in participants aged 20–40, by 1,7 in those aged 41–60, and by 1,6 in those aged 61–80. Only the first reduction was statistically distinguishable from zero.

Bone provides an exception: among 33 patients aged 65 and older, tibial fractures treated with an intramedullary nail healed as often as in younger patients (94% versus 89%), although the older patients had poorer walking ability.

Loading changes tendons. In a one-year trial, 33 people aged 62–70 trained with heavy or moderate weights or continued their usual activities. Patellar tendon thickness increased by 6% with heavy loading and 5% with moderate loading, compared with 1% without training, a difference of borderline statistical significance. Resistance to stretching was maintained only with heavy loading and declined with moderate loading and without training. Biopsies of the tendon core showed no change in collagen content or enzymatic cross-links between collagen molecules. The authors of both the radiocarbon study and the training trial suggest that the outer part of the tendon may respond to loading.