On Sep 3, 3:28Â pm, Immortalist
yahoo.com> wrote:> On Sep 2, 8:42 pm, Sir Frederick
fuzzysys.com> wrote:
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>>> How would you like to live 1,000,000 years?
>> Quantum processes are ageless.
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>> An enzyme linked to most human cancers has finally yielded its secrets – it may
>> also help defeat ageing
>> Â At the heart of almost all human cancers is a rogue enzyme, telomerase. Now the
>> structure of a key catalytic component of the enzyme has been discovered, paving
>> the way to more effective anti-cancer and, perhaps, anti-ageing drugs.
>
>> Telomerase is responsible for adding unique repetitive sequences of DNA, called
>> telomeres, at one end of chromosomes. These telomere caps ensure the chromosomes
>> don't fall apart, but because telomerase is dormant in most adult cells each
>> time a cell divides, its telomere loses a chunk of DNA. Eventually, when cells
>> can no longer divide, they die – this protects against cancer.
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>> When telomerase is more active than it should be, telomeres don't get shorter.
>> Instead, cells continue dividing beyond their normal limits, and become
>> cancerous.
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> A telomere is a region of highly repetitive DNA at the end of a linear
> chromosome that functions as a disposable buffer. Every time linear
> eukaryotic chromosomes are replicated during late S-phase the DNA
> polymerase complex is incapable of replicating all the way to the end
> of the chromosome; if it were not for telomeres, this would quickly
> result in the loss of useful genetic information, which is needed to
> sustain a cell's activities. Every time a cell with linear genes
> divides, it will lose a small piece of one of its strands of DNA. This
> process has been referred to by James Watson and Alexei Olovnikov as
> the "end replication problem" (1971).
>
> ...because of DNA replication mechanisms and because TERT expression
> is repressed in many types of human cells, the telomeres of these
> cells shrink a little bit every time a cell divides although in other
> cellular compartments which require extensive cell division, such as
> stem cells and certain white blood cells, TERT is expressed and
> telomere length is maintained.
>
> ...In most multicellular eukaryotes, telomerase is only active in germ
> cells. There are theories that the steady shortening of telomeres with
> each replication in somatic (body) cells may have a role in senescence
> and in the prevention of cancer. This is because the telomeres act as
> a sort of time-delay "fuse", eventually running out after a certain
> number of cell divisions and resulting in the eventual loss of vital
> genetic information from the cell's chromosome with future divisions.
>
> If telomeres become too short, they will potentially unfold from their
> presumed closed structure. It is thought that the cell detects this
> uncapping as DNA damage and will enter cellular senescence, growth
> arrest or apoptosis depending on the cell's genetic background (p53
> status). Uncapped telomeres also result in chromosomal fusions. Since
> this damage cannot be repaired in normal somatic cells, the cell may
> even go into apoptosis. Many aging-related diseases are linked to
> shortened telomeres. Organs deteriorate as more and more of their
> cells die off or enter cellular senescence.
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>
http://en.wikipedia.org/wiki/Telemere
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> Are Telomeres the Key to Aging and
Cancer?http://gslc.genetics.utah.edu/features/telomeres/
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>> This has made telomerase a prime target for anti-cancer and anti-ageing
>> therapies, but a lack of information on the structure of its catalytic subunit,
>> TERT, has hindered progress.
>
>> Beetle bonanza
>> Emmanuel Skordalakes and his team from The Wistar Institute, Philadelphia,
>> finally cracked the structure when they discovered that a gene in an insect –
>> the flour beetle – could be harnessed to produce the enzyme in massive
>> quantities.
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>> This enabled the team to analyse TERT using X-ray crystallography.
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>> "Structural studies of telomerase have been extremely difficult due to the size
>> and complexity of the enzyme, which in turn made it difficult to isolate the
>> protein component of telomerase in sufficient, stable quantities for the
>> proposed studies," says Skordalakes.
>
>> The structural analysis reveals that TERT (telomerase reverse transcriptase
>> protein) consists of three domains, and forms a ring-like doughnut structure
>> that creates a central hole. When the telomere is being built, this hole allows
>> a nucleic acid template molecule about eight nucleotide bases long to fit
>> inside.
>
>> Anti-ageing drug?
>> Previously scientists had thought that the structure of the enzyme is similar to
>> HIV transcriptase and developed anti-telomerase drugs accordingly. The
>> structural analysis confirms there is a similarity, but it also reveals that one
>> of the domains in the TERT protein – called the carboxy-terminal extension or
>> CTE – has a unique type of protein fold, never been seen before.
>
>> This feature could help develop anti-telomerase drugs that specifically target
>> the fold.
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>> "Now that they know what the structure of the catalytic subunit is, they can
>> design drugs that can bind to the protein subunit and either inhibit its
>> activity for anti-cancer treatment, or promote its activity as anti-ageing
>> therapy," says Stephen Neidle, from The School of Pharmacy, University of
>> London, UK.
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>> Neidle says developing drugs to target the enzyme could be used in combination
>> with existing anti-telomerase anti-cancer therapies currently in clinical
>> trials, such as a class of telomerase vaccines.
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>> Aubrey de Grey of the Methuselah Foundation says: "If we had a really cast-iron
>> therapy against all cancers, it might well be a good idea to stimulate
>> telomerase, with a drug, for example, that might have widespread anti-ageing
>> effects."
>
>> Journal reference: Nature (DOI:10/1038/nature07283)
>
>> --
>> Frederick Martin McNeill
>> Poway, California, United States of America
>> mmcne...@
fuzzysys.com
>> ******************************************
>> "I never cease being dumbfounded by the unbelievable things people believe."
>> - Leo Rosten
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I suspect the next step is to identify the psychsomatic influence over
telomerase.Particularly in 'spontanipous remission' patients.
I love living for ever, but I am also happy to inhabit new bodies. I
even get bored with my car body after a few years.
BOfL
