Weizmann and Kyoto scientists trace why human joints wear out to an evolutionary trade-off

Osteoarthritis, the painful breakdown of joint cartilage, is one of the most common causes of disability in older people, and humans seem unusually prone to it. A study published in Nature in September 2026 by Dr. David Gokhman of the Weizmann Institute of Science and Prof. Fumitaka Inoue of Kyoto University offers an evolutionary explanation, rooted in changes to the genetic switches that control how cartilage is built.

The team compared more than 15,000 human genomes with those of 139 great apes and found about 5.7 million genetic differences unique to the human lineage. Most of them do nothing. To find the ones that matter, the researchers screened variants directly in cartilage cells and identified roughly 15,000 that measurably changed gene activity. Experiments with hybrid cells that carry both human and gorilla chromosomes, grown into skeletal tissue, showed that genes responsible for making glycosaminoglycans, or GAGs, were turned down on the human chromosomes. GAGs are sugar-rich molecules that give cartilage its spring and ability to absorb shocks.

Tissue samples confirmed the effect: human knee and elbow cartilage contained only about a quarter to a third of the GAGs found in other great apes. The researchers suggest the change may be a trade-off. In the primate brain the same molecules help lock neural connections in place, so lower levels in humans may keep the brain more flexible and allow its slower development, while leaving joints less well cushioned.

Doctoral students Nadav Mishol of Gokhman's lab and Yizhi Yan of Inoue's lab led the experiments, with a team from the Institute of Evolutionary Biology in Barcelona contributing ape genomic data. The authors say that understanding which genetic switches thinned human cartilage could open new routes to treating or preventing osteoarthritis.