
Axolotl Genome Slowly Yields Secrets of Limb Regrowth - devy
https://www.quantamagazine.org/axolotl-genome-slowly-yields-secrets-of-limb-regrowth-20180702/
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reasonattlm
In terms of gaining knowledge about the most relevant mechanisms in proficient
regeneration, ARF seems important, and human ARF can shut down zebrafish
regeneration [1]. That implicates the evolution of cancer suppression
mechanisms as the reason why most higher species are not all that great at
regeneration. Further, the dance between macrophages and senescent cells
during regeneration seems highly influential in the quality of regeneration,
whether the path to scarring versus the path to regrowth is chosen. This is
found in the few examples of proficient mammalian regeneration such as the
spiny mouse [2], as well as in salamanders and zebrafish. Salamanders exhibit
much more efficient creation and clearance of senescent cells in regenerating
tissue, for example. [3]

[1]: [https://www.ucsf.edu/news/2015/11/251746/human-gene-
prevents...](https://www.ucsf.edu/news/2015/11/251746/human-gene-prevents-
regeneration-zebrafish)

[2]: [https://uknow.uky.edu/research/uk-researchers-identify-
macro...](https://uknow.uky.edu/research/uk-researchers-identify-macrophages-
key-factor-regeneration-mammals)

[3]:
[http://dx.doi.org/10.7554/eLife.05505](http://dx.doi.org/10.7554/eLife.05505)

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toomuchtodo
Based on your post and profile, mind if I ask a question?

How much further does this move us along on human regeneration as it relates
to aging?

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reasonattlm
One would have to speculate; it is very unclear. Proficient regeneration seems
like it would be a good thing to pair with restoration of stem cell function,
but without the restoration of stem cell function it might not be too helpful.

As a general rule building a new human biology is hard. Even making tiny
tweaks to our existing biochemistry, such as calorie restriction mimetics, is
proving to be very challenging to do effectively and safely. Reverting to the
known good youthful state on the other hand, is less complex. So I'd expect
delivery of replacement stem cell populations to be a going concern long
before adjustments that produce MRL-like or spiny-mouse-like regeneration in
humans.

The feature of aging that proficient regeneration seems most likely to help
with is the business of fibrosis (liver, kidney, heart, lungs), where
regeneration runs awry into excessive scarring, and damage to organs like the
heart that do not repair themselves. Equally, it might have to be controlled
very carefully in organs where structure is important, which would limit any
early application. Recent experiments with cell therapy in the heart in
monkeys produced disruption of heartbeat because of the formation of
biological pacemarkers outside the normal parameters, for example.

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fratlas
"replacement stem cell populations" You expect us to be able to revert the
ageing process through stem cells? Any stem cells or specifically those of the
host? How far off do you estimate (order of magnitude - 10/100/500 years?)

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mkempe
Red/Green/Blue Mars implies that it's within the lifespan of the current
generation between 30 and 50.

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brian-armstrong
I can’t help but feel a little bad about the mass amputation happening in
these labs. Of course these are lower animals, but don’t we lose a little of
our humanity doing this?

~~~
smt88
This is an important question, but it's also been debated to death in the
scientific community.

I have a friend who raises mice and then has to break their necks to euthanize
them before experimenting on them. Another of my friends has to give mice
cancer.

The former friend's lab has come up with life-changing treatments for muscular
diseases, and the latter friend is helping to develop immunotherapy methods.

While it's awful to think about the price, it's important to think about why
the price is paid and how much suffering can be prevented.

Another note: there are strict codes of ethics for how animals are treated in
labs, so in most reputable organizations, the suffering is as minimal as
possible (sometimes no suffering at all).

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nojvek
I really wish there was more oversight into Animals being used for testing.

Dogs are probably the most humane treated animals on the planet. I wish other
animals got the similar treatment as well.

Would love to read some of those debates. Don’t get me wrong. I am in support
for using mice for medical reasons.

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trombonechamp
In most countries, there is an ungodly large amount of oversight that goes
into animals used in scientific research. The problem is that when the media
reports animal testing, they skew the facts in order to make them sound
dramatic, when in reality animal well-being is taken very seriously. Lab mice
in general live much better lives than your pet mouse.

~~~
nojvek
I didn’t know about this. I think my impressions have mostly come from movies
like “planet of apes” so yes, they have been skewed by media.

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daemonk
I'd never thought they would actually assemble this genome. But put together
the father of string-graph assembly (Eugene Myers) and a shitload of money
(PacBio reads), and you get an assembly of a 32gb genome.

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bumblebritches5
I just looked up how large the human genome is in bits (when the 4 bases are
packed into 2 bits per base) the size of our genome is about 770MB.

Is the Axolotl's genome really 42.5 times larger than ours?

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stochastic_monk
3 billion bp in a haploid human genome, 6 billion in a full diploid one. If
you store the masked/unknown/variable ranges as annotations on the side, you
can get away with close to 2 bits per base, as you suggested.

The axolotl haploid genome is 32 Gbp, which, in 2-bit encoding and ignoring
masked bases, takes 8GB to store.

Axolotl, like humans, is diploid, meaning it has 2 copies of each chromosome.

That’s only about 10 times the size of the human genome. That being said, the
complexity of a genome doesn’t scale with size. Many plant genomes are
gargantuan but highly repetitive. The Kolmogorov complexity of a genome would
better predict the complexity of the organism than a genome’s length would.

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raverbashing
I wonder how that competes with the latest generation of Flash memory in terms
of (physical) storage size and mass.

Though storage capacity is growing, it seems DNA still wins by some margin
though

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Thiez
Flash memory has considerably better read/write speeds. It can also be read
electronically instead of chemically. I don't think it makes sense to compare
them.

~~~
stochastic_monk
It’s also error-prone. That being said, research in the area has been ongoing
for years. For example, see [0].

[0] [https://arstechnica.com/science/2013/01/mp3-files-written-
as...](https://arstechnica.com/science/2013/01/mp3-files-written-as-dna-with-
storage-density-of-2-2-petabytes-per-gram/)

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sxdx
Fascinating animals, I keep several of them as pets. Sadly they are basically
extinct.

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userbinator
The wild ones, yes. But the ones used in research and kept as pets are
essentially domesticated and breed readily.

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mr_spothawk
""" In 1952, a scientist named Charles Breedis injected coal tar and other
known carcinogens into the arms of more than 500 newts — amphibians related to
salamanders that can also regenerate. Only two animals grew tumors. Much more
often, the newts responded by sprouting an extra arm. If scientists can crack
how a carcinogen triggers that kind of regenerative growth, it would be “some
kind of holy grail” for this area of research, Whited said. """

the article has an editorial tone around the distinction of lab vs. natural
populations. it starts with an acknowledgement of the consequences of the lab
on the animals (losing limbs).

hard to argue with the holy grail, tho.

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matte_black
Is there a catch to regenerated limbs? Maybe weaker, more cancer prone, or
faster aging?

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DennisP
What I read once: when you're a wild animal in the wilderness, just scarring
over the wound sometimes gets you back in action faster than regrowing the
limb, and that's a survival advantage.

If that's the main reason evolution usually went this direction, then maybe
there's not much downside for modern folks.

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ekianjo
> they hardly get cancer

this is based on what, a few thousands individuals from that specie? on that
kind of sample size humans also hardly get cancer, unless humans get really
old. Not sure that statement can be substantiated.

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onychomys
The singular of species is species. The only person allowed to say "specie" is
Vincent Price at the beginning of Alice Cooper's song "Black Widow", because
he's a badass like that.

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stevesimmons
"specie" is money in the form of coins. Nothing badass about it!

