Re:DNA Aging, DNA Rejuvenating?
on
Goodbye, Dolly
·
· Score: 2, Informative
'DNA Aging' is nothing more than progressive telomeric shortening which is counteracted in the germ line by the action of telomerase. In the case of dolly, when she was 2 her telomeres were observed to be 80% of the length of a 'normal' sheep of that age. Not a massive difference, and not something which satisfactoraly explains her early death.
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.
Re:Oh boy...
on
Goodbye, Dolly
·
· Score: 3, Informative
Just a little point on cellular aging; i believe that the main link between 'aging' and telomeres in mamals is due to the link between the progressive shortening of telomeres and cell senesance.
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.
not to nitpick but it was part of the film not the film itself.
Also, you will see that the post was modded as 'Funny' so clearly someone/some people got the joke.
Although, it is true that it is a nice demonstration of the beauty and complexity we can find in even the simplest things.
what is also quite interesting is when you look at the european populations, the gene frequency of the mutation is greater as you get further north (and decreases almost to nothing you move down to the middle east and into africa). I beleive the gene frequency is about 11% in the UK, reaching around 13% by the time you get to Iceland. (there is a diagram of this up at uni, as one of the guys there is researching this topic.)
One of the interesting things about this mutation is that the gene is apparently quite highly conserved. People with this mutation in the homozygous form (aprox 1% of the population from hardy-weinberg) seem to be unafected by it (the mutation being recessive), but when you knockout the comparable gene in mice, they have apparently end up with a much reduced immune system.
If humans can be unaffected without this protein, it may present one of the best methods for treating HIV.
Slashdot Mirror
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.
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.
Simple, because they paid for it.
God forbid that a telecos advertising proclaiming an unlimited service with no strings attached should actually prove to be the truth.
The worrying thing for other users in the UK will be that BT and Blueyonder (and the other providers) will also employ a similar cap.
not to nitpick but it was part of the film not the film itself. Also, you will see that the post was modded as 'Funny' so clearly someone/some people got the joke. Although, it is true that it is a nice demonstration of the beauty and complexity we can find in even the simplest things.
what is also quite interesting is when you look at the european populations, the gene frequency of the mutation is greater as you get further north (and decreases almost to nothing you move down to the middle east and into africa). I beleive the gene frequency is about 11% in the UK, reaching around 13% by the time you get to Iceland. (there is a diagram of this up at uni, as one of the guys there is researching this topic.) One of the interesting things about this mutation is that the gene is apparently quite highly conserved. People with this mutation in the homozygous form (aprox 1% of the population from hardy-weinberg) seem to be unafected by it (the mutation being recessive), but when you knockout the comparable gene in mice, they have apparently end up with a much reduced immune system. If humans can be unaffected without this protein, it may present one of the best methods for treating HIV.