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Goodbye, Dolly
goombah99 writes "Dolly, the famous cloned sheep has been put to death after being diagnosed with a progressive lung disease, according to many reports. This follows on earlier reports that she was prematurely aging, including developing arthritis. While one should be cautious about drawing conclusions from a single data point, its interesting to speculate." Here is a link to her birthplace courtesy of Captain Large Face
I believe that would be mutton. Lamb chops are less than 18 months old. Dolly's chops would be, uh, less than desirable at her age.
Public use of any portable music system is a virtually guaranteed indicator of sociopathic tendencies. -- Zoso
Although the shortening of her telomeres is well-publicized, it very well may have had nothing to do with the death. A somewhat more detailed story can be found here [Reuters].
The main suspected "kink" are the telomeres, and if we do discover it's a kink, it may be a difficult one to work around. Here's a good article on telomeres and telomerase.
More than one data point. Dolly is actually the second cloned sheep to die in a week. Matilda, a cloned sheep born in the year 2000 in Australia died last week. Autopsy results were inconclusive. Matilda's passing.
$#!^ happens, but why does it always have to happen to me???
Your telomere explanation was pretty good, except that telomeres aren't just any substance. They're DNA. The end of a chromosome has short repeating sequences of a few base pairs (ex: AATTAATT, etc.) which are not all replicated when a cell duplicates its genome and divides. This presumably acts as a molecular "clock" for the organism to keep track of its "age," but this is pretty controversial and unsubstantiated.
Click here to read more about telomeres. (Why don't more people link to Wiki?)
Even if this telomere function were well-established, it doesn't entirely explain the aging process. It seems that part of the process is due to oxidative damage caused by radical reactions in the mitochondria. But similar reactions happen in chloroplasts and some plants live for millenia!The exciting thing about biology is that you reach the frontiers of knowledge in the field during your first year of introductory undergraduate coursework. In math you reach the frontiers maybe by your fourth year or in grad school. For physics and chemistry, somewhere in between. Biology is full of unexplained phenomena. If you want to make a great fundamental discovery in one of the hard sciences, then become a biologist. So much is unknown!
Found here:
Telomeres are found on the ends of chromosomes. They are a small sequence of DNA repeated many times. They act as protective "caps" and help to prevent chromosomal instability and damage. However the telomeres gradually shorten over the lifetime of the organism because they are not fully copied during cell division. The exception to this are germ-line cells, where telomeres are maintained so that full-length telomeres are passed on to the next generation.
Pretty interesting.... I didn't know that myself. Anyhow, don't thank me, thank google.
Well, it's because your gametes produce "young" DNA.
I'm sure everyone knows that the male and female gametes each produce one half of the genetic material of a single organism. The genetic material produced by the gametes is brand new; it hasn't aged yet, so the telomeres on the individual DNA strands are still intact. They recombine during fertilization and make a fresh, "young" copy of a complete DNA sequence.
"It never got weird enough for me." - HST (RIP)
Telomeres are repeating sequences of non-protein-coding DNA at the end of a chromosome. Due to an inefficiency involoved in the replication of chromosomes, they become shorter and shorter with each cell division. Eventually, the telomere is depleted and parts of actual genes begin to be cut off. This explains death by old age.
An interesting side note is that cancer cells do not undergo the shortening of telemeres unlike normal cells. As opposed to normal cells which have a finite lifetime, cancer cells are functionally immortal.
A little off topic, but still somewhat interesting.
Telomeres are not so much a substance as a sequence of base pairs located at the ends of chromosomes. They're important because the enzymes used to copy these chromosomes during cell divison can't quite go all the way to the end. In theory this means that there must be a maximum number of replications a cell can go thorugh before you start to loose important information off the end of the DNA molecule.
Some people have speculated that this may be an important cause of aging but I've never seen completely convincing research to support this. Cells do have enzymes called telomerases which can reconstitute these terminal sequences but they do shorten with each generation of cells. The whole effect is complicated.
As to using telemerase to treat Dolly - whatever the effect of telemeres is on aging, Dolly died of a "lung infection" so I don't think her chromosomes were directly to blame.
David
Please, for the love of God, stay off the dunes.
It wasn't that Dolly was a clone. Dolly was kept indoors with a bunch of other sheep (some clones, some not) and this virus was spreading in the whole population. It doesn't sound like the disease was directly related to her being a clone.
I'm trying to teach myself to set people on fire with my mind... Is it hot in here?
It is my understanding (which doesn't mean too much) that telomeres weren't so much a clock as a failsafe. When chromosomes replicate a little genetic information tends to be lost during this dividing process. Telomeres are "spare" genetic material at the ends of the chromosome, so they get cut off first. When the chromosomes in a certain cell have no telomere left, the cell cannot successfully divide.
The telomeric shortening results in the 'Hayflic Limit' where mamalian cells in culture are observed to divide 50-80 times before killing themselfs, telomeric shortening is linked to this process, prehaps providing some sort of timer as to when to kill off the cell in order to prevent conditions such as cancer.
While the telomere exists as a protection against genetic instability arising from CRISIS, I think that ascribing it a role in 'aging' is a bit of a jump. I am much more comfortable with the idea that Telomeres act to help prevent genetic instability due to the problems associated with replication of linear chromasones. While the Telomere acts as a 'molecualr clock' of sorts, it is only really concerned with the cells DNA, aging in other ways (such as progressive modifications in collagen with increased age) is nothing to do with Teleomers.
As to the point on the aging process itself, i would argue that it is entirely independent of telomeric shortening, and that change in telomeric length is *just* a timer indicating the age of the cell/number of divisions to reach its current condition. The aging process is due to a large number of ancillary effects which have no relationship to the telomeres.
And yes, biology (or in this case, not to nitpick, genetics) is one of the places where you find yourself with the cutting edge stuff very early on. Makes for really interesting study, if a bit annoying that no text book you can buy is up to date enough.
Wrong for two reasons:
1. Genetic engineering is not "random". A better comparison would be a hacker taking 10MB of source code to some random program and adding an email client. (hey, like Emacs!)
2. The genetic code can handle quite a bit of "random" mutation. There are cases where it is extremely sensitive to mutation, such as sickle-cell leukemia (single poylmorphisim that causes hemoglobin to form chains), but there are "silent" mutations and even amino acid mutations that will have no effect.
This is exactly what I wonder too. I don't get how, even if the DNA packaged in the reproductive cells ages very little over time, the human race could survive for so long. There must be something 'cleaning up' the DNA before packaging into reproductive cells.
It is Darwinian evolution. If your reproductive cells go bad, you simply don't reproduce effectively and the messed up genetics cease to continue. (Except on rare occassions the "mistakes" may be beneficial.)
Table-ized A.I.
Even if this telomere function were well-established, it doesn't entirely explain the aging process. It seems that part of the process is due to oxidative damage caused by radical reactions in the mitochondria. But similar reactions happen in chloroplasts and some plants live for millenia!
Aging is a tough problem to solve. It appears that cell reproduction errors build up over the life-time of an organism. Many of the symptoms of aging are the slowing of metabolism to reduce the chances of mistakes. If an organism is tweaked to bypass this slowdown, then cancer and similar deseases will probably end you because errors occure more often when metabolism is turned up high.
Thus, aging is a balance between a rock (slower metabolism) and a hard place (cancer).
The closest analogy that comes to mind is the basketball season. If a team plays too hard mid-season, they may have too many injuries by the time the playoffs come. And, if they don't play hard enough, they won't make it to (win enough games for) the playoffs.
Perhaps the best solution against human aging would be to slow the body's metabolism, but not the brain's. Modern living usually requires less physical exertion than our body is tuned for.
Table-ized A.I.
The most important thing to remember about the production of gametes is that they are produced by germ-line cells. Mutation is a way of life and an important evoloutionary mechanism, indeed, mutation is utilised during gamete formation (through events such as Unequal Sister Chromatid Exchange) to create a unique arrangement of genes. There is therefore no need or desire by the species to 'clean up' the dna from these muations.
In fact the lack of a mechanism for dealing with convertion of a methylated Cytosine to Thyamine has been one of the key facts which has been used to detect genes in eukaryotes - CpG islands are found with all the major housekeeping genes and ~40% of the tissue specific genes.
so in short, there is no 'clean up' (known) of the dna in the germ line, there is however a stabilisation of telomeric length (acheved through the action of telomerase) at the higher end of the 5-20kb range, which is now being rapidly charicterised.