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A question about lizard limb regeneration.


fredreload

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Let's assume I clone a lizard so there are two identical lizards in genetics, one older, one younger.

Experiment:  I cut off the arm of both the young and old lizard and stitch the old lizard's arm on the young lizard's arm place where it's cut.

Question: Would the young lizard attempt to transform the old lizard's arm into a young arm using regeneration, or would it simply shed off the old arm and grow a new one in its place?

Analysis: I am always fascinated by the idea of regeneration and I know there has to be a communication mechanism among the cells during regeneration, but I am not sure if the mechanism seeks to reprogram a cell or push it aside and grow a new cell in its place. This has a very big implication in cellular reprogramming, for instance, a hydra, which can grow from a single cell, if I want to renew its age, I just revert the age of this single cell, and it would reprogram the rest of the body to match its age. If it does not reprogram the cells then it would reprogram an entire body in place of its old ones. Which, when apply full body regeneration to the humans(hopefully in the future), would be meaningless. It would just grow an entire new body out of the existing body instead of converting the old body to match its age or structure.

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On 6/22/2019 at 9:47 AM, Bufofrog said:

Some amphibians can.

And I don't think that's the way regeneration in salamanders and newts works anyway. I've read that the blastema formed on wounds like that become the new limb.

In the wild, the newt can't go back to get its tail, nor can it sew it back to the stump, so why would the ability evolve that way? You're answer about lizards is probably true with them as well.

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They will accept and connect to the cutted off limbs if you can reattach the limbs anatomically and on a physiologically correct way. They will grow new limbs if the repositioning is incorrect and the cutted off limbs will necrotize.

Edited by FreeWill
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35 minutes ago, FreeWill said:

They will accept and connect to the cutted off limbs if you can reattach the limbs anatomically and on a physiologically correct way. They will grow new limbs if the repositioning is incorrect and the cutted off limbs will necrotize.

Do you have a link to a paper on such an experiment? Human anatomy can avoid producing scar tissue in this way, but I've just never heard of it being done on regenerating amphibians to bypass the formation of a blastema.

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1 hour ago, Phi for All said:

Do you have a link to a paper on such an experiment? Human anatomy can avoid producing scar tissue in this way, but I've just never heard of it being done on regenerating amphibians to bypass the formation of a blastema.

No I do not. Such an operation would require very special circumstances with high costs and no real informational benefit for veterinary science.

Knowing the healing potential of animals I do not exclude the possibility that such a well pland operation could not be executed on one of the lizard species. 

To answer the ops question too many animals would have to suffer for basically no real scientific benefit. 

My answer were my educated guess. 

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3 minutes ago, FreeWill said:

No I do not. Such an operation would require very special circumstances with high costs and no real informational benefit for veterinary science.

Knowing the healing potential of animals I do not exclude the possibility that such a well pland operation could not be executed on one of the lizard species. 

To answer the ops question too many animals would have to suffer for basically no real scientific benefit. 

My answer were my educated guess. 

I mistakenly thought your comments were about amphibians, since they're the ones with regenerative capabilities, not lizards. I mistakenly assumed the conversation had turned to amphibians since the OP stated that regeneration is the fascinating part, not the reattachment of limbs, and certainly not to all animals. My bad.

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19 hours ago, Phi for All said:

And I don't think that's the way regeneration in salamanders and newts works anyway. I've read that the blastema formed on wounds like that become the new limb.

In the wild, the newt can't go back to get its tail, nor can it sew it back to the stump, so why would the ability evolve that way? You're answer about lizards is probably true with them as well.

Axolotls are amazing at regeneration.  It looks like a limb from another animal may be able to be attached to an Ax.

From wiki on Axolotls:

The feature of the salamander that attracts most attention is its healing ability: the axolotl does not heal by scarring and is capable of the regeneration of entire lost appendages in a period of months, and, in certain cases, more vital structures. Some have indeed been found restoring the less vital parts of their brains. They can also readily accept transplants from other individuals, including eyes and parts of the brain—restoring these alien organs to full functionality. In some cases, axolotls have been known to repair a damaged limb, as well as regenerating an additional one, ending up with an extra appendage that makes them attractive to pet owners as a novelty. In metamorphosed individuals, however, the ability to regenerate is greatly diminished. The axolotl is therefore used as a model for the development of limbs in vertebrates.

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On 6/24/2019 at 8:26 PM, Bufofrog said:

Axolotls are amazing at regeneration.  It looks like a limb from another animal may be able to be attached to an Ax.

From wiki on Axolotls:

The feature of the salamander that attracts most attention is its healing ability: the axolotl does not heal by scarring and is capable of the regeneration of entire lost appendages in a period of months, and, in certain cases, more vital structures. Some have indeed been found restoring the less vital parts of their brains. They can also readily accept transplants from other individuals, including eyes and parts of the brain—restoring these alien organs to full functionality. In some cases, axolotls have been known to repair a damaged limb, as well as regenerating an additional one, ending up with an extra appendage that makes them attractive to pet owners as a novelty. In metamorphosed individuals, however, the ability to regenerate is greatly diminished. The axolotl is therefore used as a model for the development of limbs in vertebrates.

So you are saying the young axolotls could make the attached old axolotls arm into a young axolotls arm using regenerative technique? That is amazing. Though I do like to know the mechanism of action that the young axolotls is doing to the old axolotls arm. Does it reverse ages the arm using a hormone with the repair action?

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48 minutes ago, fredreload said:

So you are saying the young axolotls could make the attached old axolotls arm into a young axolotls arm using regenerative technique?

That's not what I got from that. "Restoring to full functionality" doesn't mean "reversed the aging process". I didn't read anything about changing the age of any cells to match with any other cells. 

It sounds more like the salamanders can regenerate the bond with a severed limb, but sometimes a blastema also forms, growing an extra limb (eye, brain parts, etc) from the cells. It's clear that transplants between individual salamanders works, but it doesn't sound like there is any deterioration due to age being reversed in the regeneration process.

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3 hours ago, Phi for All said:

That's not what I got from that. "Restoring to full functionality" doesn't mean "reversed the aging process". I didn't read anything about changing the age of any cells to match with any other cells. 

It sounds more like the salamanders can regenerate the bond with a severed limb, but sometimes a blastema also forms, growing an extra limb (eye, brain parts, etc) from the cells. It's clear that transplants between individual salamanders works, but it doesn't sound like there is any deterioration due to age being reversed in the regeneration process.

Agreed.

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5 hours ago, fredreload said:

Well, then we must assume that regeneration would not help in biological immortality, making biological immortality a bit far fetched.

Once again, agreed.  Research into the regeneration ability of the axolotl could help with understanding how to restore a lost limb in humans.

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2 hours ago, Bufofrog said:

Once again, agreed.  Research into the regeneration ability of the axolotl could help with understanding how to restore a lost limb in humans.

Well, it might induce apoptosis on the surrounding cells and update the limb for the older axolotl arm.

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On 6/26/2019 at 7:50 AM, fredreload said:

Well, it might induce apoptosis on the surrounding cells and update the limb for the older axolotl arm.

Iirc, apoptosis is less of an "update" in terms of cell age, and more of a cleaning out of unnecessary bits (a refresh as opposed to a reset?). It's not a rejuvenation. It's more like the cell is a file folder, and periodically needs evaluation to remove the pages and pictures and  sticky notes that don't need to be kept in that folder anymore, for whatever reason (very limited analogy, don't take it too far).

Can you cite a good source claiming it's more like a reset button? Or did I misread what you're saying?

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On 6/26/2019 at 1:43 PM, Bufofrog said:

Research into the regeneration ability of the axolotl could help with understanding how to restore a lost limb in humans.

Regeneration isn't a simple process. The body would need to be able to recognize and select the exact genetic information the limb is based upon.

The body would need to be able(have the DNA) to activate and execute the limb forming process, which supposed to be a development from an almost embryonic state to a fully evolved human limb.

To reach regeneration in humans is very difficult (we are far too "complex").

A limb could be 3D cultured/printed based upon the customers DNA. When the limb is ready reattach the limb to the body. Such surgical processes already developed. We have to wait on technology a bit to have the right legs.

Edited by FreeWill
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21 hours ago, Phi for All said:

Iirc, apoptosis is less of an "update" in terms of cell age, and more of a cleaning out of unnecessary bits (a refresh as opposed to a reset?). It's not a rejuvenation. It's more like the cell is a file folder, and periodically needs evaluation to remove the pages and pictures and  sticky notes that don't need to be kept in that folder anymore, for whatever reason (very limited analogy, don't take it too far).

Can you cite a good source claiming it's more like a reset button? Or did I misread what you're saying?

Hi, Freewilll has a more complete picture about what I am trying to describe, I will add on to that.

20 hours ago, FreeWill said:

Regeneration isn't a simple process. The body would need to be able to recognize and select the exact genetic information the limb is based upon.

The body would need to be able(have the DNA) to activate and execute the limb forming process, which supposed to be a development from an almost embryonic state to a fully evolved human limb.

To reach regeneration in humans is very difficult (we are far too "complex").

A limb could be 3D cultured/printed based upon the customers DNA. When the limb is ready reattach the limb to the body. Such surgical processes already developed. We have to wait on technology a bit to have the right legs.

There are two things I am interested about regeneration. I want to achieve head regeneration in human, complete with brain and everything. The idea is that it could achieve immortality, and even cloning would not suffice such a result if assume that the regenerated head brings back the head. Second, I want to achieve reverse aging through regeneration. Though based on your idea of going through embryonic stem cells part by part is not exactly the most efficient way of reverse aging. But your theory is correct, I agree with you.

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To begin with, let's make a distinction about regeneration of the head and embryonic growth of the head. Regeneration of the head matches the age of the individual, you don't grow an infant's head on an adult body, you grow an adult head on an adult body, this step presumably follows the part where the embryonic stem cells have differentiated in accelerated aging. If you assume a perfect regeneration of the head, then it would comes with the original person's consciousness as well as original person's memory(brain structure remapped through regeneration, I am not sure how). All that being stored somewhere(in the neighboring cells?), I assume the acceleration of aging is a factor for the original person's consciousness and original person's memory.

If you make a clone body, it does not come with original person's memory and original person's consciousness.

P.S. Not many creatures can regenerate a head, I think hydra is one of them.

Edited by fredreload
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22 hours ago, FreeWill said:

To reach regeneration in humans is very difficult (we are far too "complex").

Not true. What about the embryonic regenerative cycle? Isn't that why scientists have hope for regeneration, because we already have elements in place?

3 minutes ago, fredreload said:

Regeneration of the head matches the age of the individual, you don't grow an infant's head on an adult body, you grow an adult head on an adult body, this step presumably follows the part where the embryonic stem cells have differentiated in accelerate aging. If you assume a perfect regeneration of the head, then it would comes with the original person's consciousness as well as original person's memory. All that being stored somewhere, I assume the acceleration of aging is a factor for the original person's consciousness and original person's memory.

Wow, those are some major assumptions. Why would regeneration affect memory and consciousness?

This is no longer interesting to me. Too many wild-ass guesses with no basis. I think regeneration holds some very promising benefits for humans, but I think it will be more like growing new teeth rather than replicating identical copies of people.

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1 hour ago, FreeWill said:

So why human regeneration is easy if it isn't difficult and where I can read about successfull human regeneration?

https://en.m.wikipedia.org/wiki/Regeneration_in_humans

Generally pretty limited but this might perhaps be changed.

It won't preserve the network of neurons that makes up you though.

 

@fredreload

Cells do not have an age. Their components wear down or are altered over time. The cell then either needs to be repaired or replaced.

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1 hour ago, FreeWill said:

So why human regeneration is easy if it isn't difficult and where I can read about successfull human regeneration?

Right after I wrote "not true", I wrote, "What about the embryonic regenerative cycle?" I would start with that. 

Human regeneration is easy if you're an embryo.

15 minutes ago, Endy0816 said:

Cells do not have an age. Their components wear down or are altered over time. The cell then either needs to be repaired or replaced.

Exactly. Aging is more of a wearing down of function within an organism as a whole. That's what causes cellular repair and replacement to deteriorate over time, isn't it? The cells don't get old, but as we age the processes used to repair/replace them decrease in efficiency. 

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15 hours ago, Phi for All said:

Wow, those are some major assumptions. Why would regeneration affect memory and consciousness?

This is no longer interesting to me. Too many wild-ass guesses with no basis. I think regeneration holds some very promising benefits for humans, but I think it will be more like growing new teeth rather than replicating identical copies of people.

If I am a salamander missing a "right arm", I would grow a "right arm" back instead of a "right foot" where my "right arm" should reside. Where do you think the blue print for this "right arm" is stored? How does the salmander's body remember the structure of this "right arm"? Same goes for the memory and consciousness, if I am a salamander and I am missing a "right brain", it should regenerate the neuronal structure that matches the memory and consciousness of the "right brain", but not a blank slate. Just an assumption.

Q1:

So if a salamander's arm is injured I would regenerate an injured arm?

A1:

Not quite, the neuronal structure and positioning of the neurons resides in the epigenetics of the DNA, and therefore could be remembered during regeneration. An injury does not alter the epigenetic state(I think?).

Q2:

So where is the DNA blueprint for this salamander's "right arm", would it remember the epigenetic state of the neuronal structure of the brain?

A2:

Ionno, same thing how am embryo grows into a human body, there is a blueprint for the human body in the embryo, no idea on the epigenetic state, just an assumption.

Q3:

Can I insert this epigenetic state into a newly develops embryo so it forms the consciousness and memory of the other human?

A3:

That my friend, is the question. During the dog cloning research the newly cloned dog seems to have the memory of the old dog. At one instance the dog seems to remember how to open a fridge in which it is not trained to open a fridge. Again, could be a science fiction. I will have to find the video after I get enough sleep.

Q4:

Why would a cloned dog contains the memory of the previous dog?

A4:

The dog is cloned using the previous dog's DNA with the Dolly Sheep cloning procedure. So it does not exactly start out from scratch, maybe the epigenetic state of the neuronal structures of the brain of the previous dog is transferred to the clone in this way.

Edited by fredreload
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15 hours ago, Phi for All said:

Right after I wrote "not true", I wrote, "What about the embryonic regenerative cycle?" I would start with that. 

Human regeneration is easy if you're an embryo.

Exactly. Aging is more of a wearing down of function within an organism as a whole. That's what causes cellular repair and replacement to deteriorate over time, isn't it? The cells don't get old, but as we age the processes used to repair/replace them decrease in efficiency. 

Yep.

Might caveat that division is halting deliberately as a result of repair limitations though. Safer for continuing the germline and you as a whole.

 

2 hours ago, fredreload said:

If I am a salamander missing a "right arm", I would grow a "right arm" back instead of a "right foot" where my "right arm" should reside. Where do you think the blue print for this "right arm" is stored? How does the salmander's body remember the structure of this "right arm"? Same goes for the memory and consciousness, if I am a salamander and I am missing a "right brain", it should regenerate the neuronal structure that matches the memory and consciousness of the "right brain", but not a blank slate. Just an assumption.

Q1:

So if a salamander's arm is injured I would regenerate an injured arm?

A1:

Not quite, the neuronal structure and positioning of the neurons resides in the epigenetics of the DNA, and therefore could be remembered during regeneration. An injury does not alter the epigenetic state(I think?).

Q2:

So where is the DNA blueprint for this salamander's "right arm", would it remember the epigenetic state of the neuronal structure of the brain?

A2:

Ionno, same thing how am embryo grows into a human body, there is a blueprint for the human body in the embryo, no idea on the epigenetic state, just an assumption.

Q3:

Can I insert this epigenetic state into a newly develops embryo so it forms the consciousness and memory of the other human?

A3:

That my friend, is the question. During the dog cloning research the newly cloned dog seems to have the memory of the old dog. At one instance the dog seems to remember how to open a fridge in which it is not trained to open a fridge. Again, could be a science fiction. I will have to find the video after I get enough sleep.

Q4:

Why would a cloned dog contains the memory of the previous dog?

A4:

The dog is cloned using the previous dog's DNA with the Dolly Sheep cloning procedure. So it does not exactly start out from scratch, maybe the epigenetic state of the neuronal structures of the brain of the previous dog is transferred to the clone in this way.

 

Memories don't rransfer. There's too much data involved.

Edited by Endy0816
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2 hours ago, Endy0816 said:

Memories don't rransfer. There's too much data involved.

Alright, even if it isn't stored, there might be a way to program it into the embryo. The formation of the neuronal structure in the embryo is not random, it is a combination of epigenetics from the father's and mother's side. Though it is true that we are born without any memory, beats me =/.

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