Repeated Regeneration

A 16-year-long newt study finds that regeneration remains efficient with repetition and age.

By | July 12, 2011

Cynops pyrrhogasterWIKIMEDIA COMMONS, DOBROMILA

Adult newts retained the complete and robust ability to regenerate their eye lenses 18 times over a 16-year period, according to a study published today (July 12) in Nature Communications.

The finding counters the belief that regeneration becomes less efficient with time or repetition. It also gives hope to regenerative medicine that age may not affect regeneration ability.

“It’s very surprising that the lenses the newts regenerate look really very similar to the [original] lens,” said Brigitte Galliot, who studies hydra regeneration at the University of Geneva in Switzerland and was not involved in the research. “It’s unusual to have a study over 16 years,” she added. “It’s beautiful material.”

Regeneration studies conducted in the 1700s and 1800s noted that repeated limb amputation and regeneration in newts occasionally resulted in missing bone structures. This led to the belief that the regenerating capacity of newts and other animals declines with age or repetition. Since then, scientists have suggested that maybe those experimenters occasionally amputated the entire limb instead of most of it, in which case the limb will not grow back. “In every seminar I give, that question comes up,” says senior author Panagiotis Tsonis, a regeneration researcher at the University of Dayton in Ohio. “Until now, I couldn’t answer it.”

In 1994, Goro Eguchi at the National Institutes for Natural Sciences in Japan began collecting long-lived Japanese newts, Cynops pyrrhogaster. With a cohort of 12 animals, each an estimated 14 years old when captured, Eguchi began systematically removing the lenses from the eyes of the newts, a rapidly regenerating organ.

A few years ago, when Eguchi retired, he passed the experiment onto Tsonis, his past graduate student. By that time, only six of the animals were still alive. Tsonis continued the experiment until last year, when he removed lenses from the six animals two final times, extraction number 17 and 18, when the animals were about 30 years old.

The 17th and 18th regenerated lenses were examined for morphology and mRNA expression, including transcripts for key lens structural proteins. The results were compared to the earlier regenerated lenses, as analyzed by Eguchi, and to original lenses from adult offspring of the test newts, bred by Eguchi 16 years ago as a way to exclude variation from un-related individuals.

Control lens (A and B) as compared to regenerated lens #17 (C and D). B and D show arrangement of fibers in the lens.
Control lens (A and B) as compared to regenerated lens #17 (C and D). B and D show arrangement of fibers in the lens.
COURTESY OF PANAGIOTIS TSONIS, UNIVERSITY OF DAYTON

In size, shape, transparency and gene expression patterns, the regenerated lenses were virtually identical to the control lenses. The lenses also took the same amount of time to completely regenerate—about 5 months—throughout all 18 repetitions of the procedure, demonstrating that there is no delay in or slowing of the process of lens regeneration over time or through repeated regeneration.

“The results were really spectacular,” said Tsonis. “They were so robust when we compared among [the 18 generations] or with control newts.”

Scientists still lack data about repeated regeneration during the juvenile stage, as the study began with adult newts, noted Galliot. Also, the paper did not address other aging criteria besides time, such as molecular and genetic markers. “It would be interesting to know more about aging and regeneration in the newt,” she added. “There are still plenty of questions.”

But the results offer hope for regenerative medicine, the effort to restore the structure or function of damaged tissues in humans. Though people may never regenerate like the newt, the 30-year-old newts suggest that regeneration can work well and robustly in older populations, says Tsonis. “It’s good to know that the animal who is the champion of regeneration doesn’t care about age.”

G. Eguchi, et al., “Regenerative capacity in newts is not altered by repeated regeneration and ageing,” Nat Comm, doi:10.1038/ncomms1389, 2011.

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Comments

Avatar of: S. Huang

Anonymous

July 12, 2011

Sorry to be negative but I do not see why this offers hope to regenerative medicine.

Regeneration in newt is a fundamentally completely distinct process from the equivalent (wound healing, at best) in humans:  Regeneration of entire tissues (limb, lens) relies on mature cells to DE-differentiate into stem-cell like blastema cells. Humans would healing (the best we can do) depends on existing resident "self-renewing" stem cells whose abundance decreases with age. The difference is due to the difference in the topography of the attractor landscape which in turn is of course determined by the wiring diagram of the gene regulatory nework.

Of course we can try to manipulate the GRN to achieve retro/de-differentiation. But since the landscape structure does not possess the chreods to guide the artificially dedifferentiated cells into the normal path of development for tissue repair, we may instead end yup with a tumor.

Avatar of: HC

Anonymous

July 12, 2011

It would be interesting to see how long regenerating organisms can live. Could this be studied with simple earthworms? Could they potentially live
"forever"? If not, it would be interesting to understand why not.

Avatar of:

Posts: 0

July 12, 2011

Sorry to be negative but I do not see why this offers hope to regenerative medicine.

Regeneration in newt is a fundamentally completely distinct process from the equivalent (wound healing, at best) in humans:  Regeneration of entire tissues (limb, lens) relies on mature cells to DE-differentiate into stem-cell like blastema cells. Humans would healing (the best we can do) depends on existing resident "self-renewing" stem cells whose abundance decreases with age. The difference is due to the difference in the topography of the attractor landscape which in turn is of course determined by the wiring diagram of the gene regulatory nework.

Of course we can try to manipulate the GRN to achieve retro/de-differentiation. But since the landscape structure does not possess the chreods to guide the artificially dedifferentiated cells into the normal path of development for tissue repair, we may instead end yup with a tumor.

Avatar of:

Posts: 0

July 12, 2011

It would be interesting to see how long regenerating organisms can live. Could this be studied with simple earthworms? Could they potentially live
"forever"? If not, it would be interesting to understand why not.

Avatar of:

Posts: 0

July 12, 2011

Sorry to be negative but I do not see why this offers hope to regenerative medicine.

Regeneration in newt is a fundamentally completely distinct process from the equivalent (wound healing, at best) in humans:  Regeneration of entire tissues (limb, lens) relies on mature cells to DE-differentiate into stem-cell like blastema cells. Humans would healing (the best we can do) depends on existing resident "self-renewing" stem cells whose abundance decreases with age. The difference is due to the difference in the topography of the attractor landscape which in turn is of course determined by the wiring diagram of the gene regulatory nework.

Of course we can try to manipulate the GRN to achieve retro/de-differentiation. But since the landscape structure does not possess the chreods to guide the artificially dedifferentiated cells into the normal path of development for tissue repair, we may instead end yup with a tumor.

Avatar of:

Posts: 0

July 12, 2011

It would be interesting to see how long regenerating organisms can live. Could this be studied with simple earthworms? Could they potentially live
"forever"? If not, it would be interesting to understand why not.

Avatar of:

Posts: 0

July 13, 2011

I agree with Huang. But I may add here two points. 1) Luckily this is happening to lens inside a previleged organ-- the eye. 2) But is it repeated 'biosynthesis' or repeated 'regeneration' ?.

Avatar of:

Posts: 0

July 13, 2011

I agree with Huang. But I may add here two points. 1) Luckily this is happening to lens inside a previleged organ-- the eye. 2) But is it repeated 'biosynthesis' or repeated 'regeneration' ?.

Avatar of: PSRMurthy

Anonymous

July 13, 2011

I agree with Huang. But I may add here two points. 1) Luckily this is happening to lens inside a previleged organ-- the eye. 2) But is it repeated 'biosynthesis' or repeated 'regeneration' ?.

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