For nearly 250 years, generations of scientists believed that the older an animal gets, the less able it is to regenerate and replace damaged or diseased tissue. (Even Charles Darwin weighed in.) Everyone assumed that, as animals age, cellular resources become exhausted, DNA repair mechanisms break down, healing takes longer and tumors develop. As of today, however, that’s no longer the doctrine. It still might be harder and harder for humans to repair wounds and heal as we age, but it turns out that the humble newt is another story.
When injured, newts can regenerate limbs, tails or eyes right back to factory standards. Humans can only do that at the very tip of the finger and only under very limited circumstances. And according to a new study published today in the journal Nature Communications, old newts can do it just as well as young newts. The study focused on the newt’s optical lens, which can be removed entirely and, after the incision heals, completely regenerate in a single day. The study’s lead author, Dr. Goro Eguchi, began breeding newts and collecting lenses 16 years ago. Throughout the years since, lenses were removed 18 times from the same animals. By the time of the last tissue collection, they were at least 30 years old (very old, for a newt).
The main finding of this paper is simple, but powerful: the last two regenerated lenses of each animal (the 17th and 18th) were virtually identical to intact lenses removed from full-grown newts that had never undergone lens regeneration. Everything—appearance, growth rate and even gene expression—was the same.
Not only does this turn an evolutionary dogma on its head, it’s also good news for human medicine.
“Humans may not be able to regenerate tissue the way a newt can—or keep doing it far into old age—but now we at least know that it’s biologically possible. And if we can understand how the newt is able to do this, perhaps we can understand why humans can’t and eventually find a way to recapitulate old-age regeneration,” explains Dr. José Luis Millán, professor in the Institute’s Sanford Children’s Health Research Center and co-author of the study.
Dr. Millán, better known for his work on a rare inherited bone disease, got involved with this study because he has been friends with the study’s senior author, Dr. Panagiotis Tsonis, for 30 years. They did their postdoctoral training together at Sanford-Burnham in the 1980s, back when the Institute was known as the La Jolla Cancer Research Foundation. So when Dr. Tsonis (now director of the University of Dayton’s Center for Tissue Regeneration and Engineering at Dayton and adjunct professor at Sanford-Burnham) needed someone to help carefully analyze each delicate little lens, he knew he could count on Dr. Millán and his lab.
“This study took an immense amount of care and perseverance over several decades,” Dr. Tsonis says. “Because it takes so long to breed and age newts, we couldn’t afford to waste a single lens. Fortunately, thanks to Dr. Eguchi’s initial dedication and later collaboration with Dr. Millán, we succeeded, obtaining accurate data from every one we collected. That’s why we can conclusively say there was no difference between the 17th or 18th lenses and any of the younger ones.”
What’s next for the newts?
Drs. Tsonis and Millán are now thinking about comparing stem cell-like cells in the newt to human embryonic stem cells and induced pluripotent stem cells (iPSCs). They believe that comparing all the genes and proteins that allow these cells to proliferate, differentiate and repair damaged DNA could provide significant insight into the regeneration process and how it might help advance regenerative medicine for humans.
For more information, read the University of Dayton’s press release or watch Dr. Tsonis describe this research in the video below:
This study was also highlighted by The Scientist (“Repeated Regeneration“) and Discover Magazine‘s Not Exactly Rocket Science blog (“Newt healing factors unaffected by age and injury“).
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Original paper:
Eguchi, G., Eguchi, Y., Nakamura, K., Yadav, M., Millán, J., & Tsonis, P. (2011). Regenerative capacity in newts is not altered by repeated regeneration and ageing Nature Communications, 2 DOI: 10.1038/ncomms1389
