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Cloned sheep shows signs of premature aging
Wonko42 writes "Everyone's favorite cloned sheep, Dolly, is showing signs of premature aging. Even though she's only three years old, her cells are acting like they're six years old. Scientists think this is because she was cloned using cells from an older sheep. "
The sheep is a clone. The whole point is that it has the same DNA as the original. No DNA modification involved.
At least, that's how I learned how things work from horror movies.
7x10^5? What does this refer to? The average human cell can divide 50 (+/-10) times before dying (undergoing apoptosis to be technical).
All the numbers I have seen are in this range (around 50), but keep in mind that they are for cells in a culture dish, not cells in the body... and of course there is a fair degree of variation among cell types.
I don't think we've had immortal eukaryotic cell lines for 80 years, but I could be wrong. Where did that number come from? This is not intended as flamebait. I'm just curious.
That number has to be bogus, as you've alluded to with your calculation. I think the HeLa cell line goes back to the 60s or 70s.
Another way of looking at this number is to realize that if a cell can divide 7e+5 times then you would end up with 2^7e+5 cells. I don't have a calculator on hand that can deal with a number this big, but approximating 2^4 = 10 (a nice margin of underestimation), that converts to about 1e+17500.
Assume that the average cell is a cube 20 microns on a side, or 8e-15 cubic meters each. Then the volume of all these cells is approximately 1e+17486 meters cubed! A sphere of this volume would have diameter well in excess of 1e+5700 kilometers.
A light year is about 9e+12 kilometers, so this sphere of cells would have a diameter of well over 1e+5600 light years!
I suspect that this is larger than the estimated size of the universe, but I don't have a hard figure there. I do know that my physics text says that we can see quasars up to 1e+10 light years away.
Those exponents sure do balloon quickly.
Its been known for some time now that most cells don't live forever. I think it has actually been calcualted that human cells will only devide X numer of times before they stop working very well (where X is a number around 7x10^5 or so).
Some cells don't have this problem- noteably stem cells (the cells in your bone marrow from which all other cells come from) and cancerous cells. (!!!) I would have thought that Dolly would have been cloned from a stem cell. Maybe this was not possible when she was, uh, created.
The part of the article about telomeres is fairly accurate. Due to the way that DNA replicates, the ends of the chromosomes are not copied properly. There is an enzyme called telomerase that adresses this problem by capping the ends of the chromosome on each replication. (This also keeps the ends of the DNA from being degraded by enzymes in the cell's endoplasm). But telomerase doesn't do its job perfectly and the chromosome eventually starts to loose important parts of its DNA. How or even if this then triggers a self-destruct process in the cell is not really understood. Perhaps cloning can be used to study this.
2^5
The article claims that she started with over-aged cells, and thus "inherits" this agge, but that her offspring would be normal. But would they? This would require some type of "repair" of here gametes, as her ovaries will have been formed from the wrong "age" of cells. Even presuming something about ovaries and testes that avoids the general agin effect, might this only fix cells to the age of those (normally a couple of days) forming the organs?
The article points out that this may cause the sheep to die earlier than expected as all the cells are older. I would think that there would be other complications (or benefits) as well. As people age, their metabolism slows down. They also get wrinkly, smell funny, and go bald. Cloning of animals may finally help us to understand how aging works. Is it a result of time upon the body, or is it a result of genetics? We may even get some medical benefits as the body fights disease differently with age and we could start people off at an optimal age for immune system development (not being a doctor, this may well be birth).
:)
And if humans are ever cloned, what does this mean for things like Senior Citizen discounts and Social Security (I know this doesn't necessarily apply outside of the US). Is someone 65 years old because they've been on this planet for 65 years or because their cells say they're 65? Perhaps these old people who are climbing mountains and water skiing barefoot on one leg aren't really old, they've just been around for a while.
I wonder now what impact this will have on Richard Seed's infertility work...
You're spot on. My wife (internal medicine physician) tells me we're already seeing the following adaptation: richer people have been demanding (and getting) antibiotics for just about everything, including minor viral ailments where antibiotics don't do any good...but the loud, litigious rich folks with a sense of supreme entitlement push and scream, and so many docs give them the antibiotics they demand. So...over time these richer folks have become "immuno-compromised", so that if they have a REAL infection, sometimes they get really sick (and even die) because their virii and bacteria are inured to Biaxin, etc. Whereas Joe Worker, ordinary guy who's avoided doctors for the most part, is easily and successfully treated if he gets a serious infection. Just goes to show, even within our normal lifespan, the bugs in our bodies can evolve quite quickly.
>Other researchers said the finding does not >have serious implications for agriculture.
i like this quote...now lets wait a few years till some real hard data comes out (like doing some studies on all those ppl sucking on their soya milk )...till then its non genetically modified for me! (if only i could tell the difference)
peterrenshaw ~ Another Scrappy Startup
Some of these are raised in the article. We live in interesting times!
Odd that you say that. "May you live in interesting times" is an old (Chinese, I believe) curse.
--
Michael Chisari
dominion@beyondtheweb.com
Ok here are the problems with this report.
One studying a single clone is like studying a single human being and trying to derive that what that human goes through all humans will do. If you
were to study me, you would assume that all humans
are left handed, far-sighted, like Free Software,
and are green eyed.
So dolly is showing some age in her genes. It could be due to telomere damage that was not corrected by the cell during incubation, or it could be a sign that her genes are a statistical
anomoly...
The problem with reading too much into this report is that if her mother was 6 years old when the cloning was done, and Dolly is 3 years old then shouldnt the damage be that of a sheep that is a nine year old sheep if no telomere damage had been averted. (Or did I misread something)
-- SJS smooge at smoogespace dot com
Here are some links for more information.
--Karl
Some things to ponder:
What "apparent" age will the Dolly^2 have? Can we do any comparisons between Dolly, the original donor, and Dolly's clone? Is a clone of a clone even feasible?
Some of these are raised in the article. We live in interesting times!
--
"May I have ten thousand marbles, please?"
Clone the clone, then clone that clone, then clone that clone, etc...
If it stops working at some point we are missing a key element. If it doesn't stop working then we know that something about the enviroment of the host egg is resetting the genetic component of the aging process.
By the way, the Tolomere theory is just one theory of aging. The fact that Dolly's tolomeres were shorter than average for a sheep her physical age does not neccessary lead to the conclusion that she is in some way prematurely aged.
-josh
I just thought I'd add this to the gene blender.
Heard on the radio this morning, that the 6 billionth human is expected to be born in mid October. That's an awful lot of people on one mudball.
Now, with Dolly, or Polly, or however many clones we make - giving us a shot at immortality in the long run, how will we do this responsibly?
It only took a dozen years since we crossed the 5 billion population threshold to make another billion the old-fashioned way.
Most of the earth's population is living in poor conditions.
Buckminster Fuller proposed that the earth can easily support 10 billion people at luxurious quality of life, if we're responsible about it.
We're not responsible.
With cloning of humans a not-too-distant possibilty (humor me) and the natural population increase rate itself increasing; I hope NASA is doing it's job.
-- It's all for nothing, unless we go to the stars.
-- What you do today will cost you a day of your life.
The article that I read in the NY Times had some countervailing opinion. The size of the decrease is at the limits of the resolution of the measuring technique. We also don't know enough about natural variation in the size of telomeres to tell if the decrease is stastically significant.
I have discovered a truly marvelous sig, unfortunately the sig limit is too small to contain i
We have cells in our lab that were harvested from a lady named Helen ~30 years ago(Hela cells) and they are still alive and kicking while Helen is not. This cells are very screwed up(>90 chromasomes) and they have active telmerase.
I believe her name was actually Henrietta Lacks. Reader's Digest had a story about her some years ago. Her cells were widely used in cancer research and were known for "contaminating" other cell cultures, so that researchers who thought they were testing treatments on multiple cell cultures found that they were actually testing only HeLa cultures.
My big concern, is that we'll have 200, or 8000 year old goats and great^20 grandmama's running around(well moseying perhaps), and that's a DAMN long time as far as bacteria & virii are concerned.
A hell of a lot of adaptation could occur in 200 years in a human host with non-changing genetic material. If we suddenly have arbitrarily long lifespans, will they adapt in amazing new ways to our code? Will these super-adapted virii be able to infect all humans, or will they adapt to a specific host?
Kinda scary to me...
--
-- Spankmeister General
Don't forget that Dolly's short telomeres were completely expected, which is a good sign - it's further proof that telomeres are intimately related to aging. Given the exponential rise in genetic knowledge, anyone under 30 today can reasonably expect to live forever, reset to the 'default' physical age of 25, even if they've aged beyond that in the meantime.
Of course, since dying itself is simply an evolved cellular-level defence against cancer, let's hope cancer is solved along the way.... (and before anyone answers the obvious point raised here, remember that evolution favours individual genes, not individual animals.)
- Read fiction at www.espressostories.com
See also:
http://www.newscientist.com/ns/9 81107/nshorts.html for a short note about the paper published in Science (Search for Benzer, free registration needed to read the abstract).
There is also a fantastic article on Seymour Benzer in the April 5 issue of the New Yorker.
You know, with short replicant lifespans.
Certainly no one thought Philip K. Dick's novel was meant to be an accurate predictor of the future, and yet it's becoming more and more like the Bible of the 21st century. The real question is: Were the images of Dick (and Ridley Scott) accurate predictions of the future, or did those images play some role in creating the reality they predicted?
It seems to me that if we grant the idea that images of the future tend to construct the future, then we've got a pretty nasty road ahead. I can think of a lot more dystopian sci-fi images than hopeful, positive ones.
He who refuses to do arithmetic is doomed to talk nonsense.
Well the computing solution would be to switch from using checksums to spot bad cells as it seems to do now and start using hamming coded DNA.
That might take a few technology advances yet
Evidence has been mounting that a cell's lifespan has a genetic basis. It's not, in otherwords, that cells suffer damage until they eventually 'give out'. Rather, some cells have a genetic cron|kill function.
Now the trick is going to be to figure out how to reset the function.
Immortality, anyone?
What is happening to Dolly's clones is a predictable event and one which did not surprise me at all. It simply proves a point.
Eucaryotes(aka multicellular life forms) have linear Chromosomes as opposed to prokaryotes(bacteria) which have circular chromosomes. Each time a linear chromasome replicates thru cell division, it losses some of its ends. This is called degenerate replication. An enzyme with an RNA core (used as a template) is used by the cell to replace the bases that can not be replicated and it is called Telomerase. The strech of DNA that is shortening is called the Telemere. Normally, telomerase is NOT active in cells other than in very early life(before the 2nd trimester). Although it has been found in some cells in the adult. Those cells are believed to be the pluripotent stem cells(capable of forming just about any cell in the body) and CANCER cells. If a cell wants to live forever, telomerase will have to reawaken and repair its ends if it does not, the belief in the scientific community is that the cell will undergo "Programmed death" (aka apoptosis) when the telemeres on the ends of the chromosome gets to short. An example of this principle can be seen in the disease ATAXIA TELANGIESIA (AT). These poor souls are born with abherently short telomeres and by the age of 18, the individuals resemble a 70 year old.
With that said, the DNA that was used for Dolly's clones was obtained from the breast of Dolly and the cells were fully differentiated and thus had already undergone significant shortening of the chromosome before the DNA was harvested. One would expect several things to happen. 1) DNA will age faster due to telemeric shortening and 2) DNA will have acumulated mutations from Dolly's life as well as from its own life and thus will have a higher disposition for cancer. I define cancer as the acuumulation of mutations that allows for genes to be disregulated and thus cells live when they should die. We have cells in our lab that were harvested from a lady named Helen ~30 years ago(Hela cells) and they are still alive and kicking while Helen is not. This cells are very screwed up(>90 chromasomes) and they have active telmerase.
Cloning promises many good things....
All I worry is that the rich people of this world, that everybody hates, clone themselves!!!!!
Think of it...
A troop of Trumps...
a swarm of Simmons (Richard! ack!)
We must make laws against this abuse of science, everyone!!