Young animals recover from tissue damage better than adults, and from Charles Darwin's time until now, scientists have puzzled over why this is the case. A study published by Cell Press November 7th in the journal Cell has revealed that an evolutionarily conserved gene called Lin28a, which is very active in embryos but not in adults, enhances tissue repair after injury when reactivated in adult mice. The findings open up new avenues for the treatment of injuries and degenerative diseases in adult humans.
"It sounds like science fiction, but Lin28a could be part of a healing cocktail that gives adults the superior tissue repair seen in juvenile animals," says senior study author George Daley of Boston Children's Hospital and Harvard Medical School.
Tissue repair is more robust in juveniles than in adults throughout the evolutionary spectrum of organisms, from insects and amphibians to fish and mammals. The molecular causes of this phenomenon have been elusive, but Daley and his collaborators speculated that the Lin28a protein could play a role because it regulates growth and development in juveniles, but its levels decline with age.
To test whether this protein might influence tissue repair in adults, Daley and his team reactivated the Lin28a gene in adult mice. Lin28a enhanced hair regrowth in these mice after they were shaved, and promoted tissue repair in their ears and digits after injury. The protein also stimulated cell proliferation and migration, which are critical for tissue repair. Lin28a achieved all of these effects by increasing the production of several metabolic enzymes and enhancing metabolic processes that are normally more active in embryos.
"We were surprised that what was previously believed to be a mundane cellular 'housekeeping' function would be so important for tissue repair," says study author Shyh-Chang Ng of Harvard Medical School. "One of our experiments showed that bypassing Lin28a and directly activating mitochondrial metabolism with a small-molecule compound also had the effect of enhancing wound healing, suggesting that it could be possible to use drugs to promote tissue repair in humans."
Cell, Shyh-Chang et al.: "Lin28a enhances tissue repair by reprogramming cellular metabolism."