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Molecular Mechanisms of Cellular Stability


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#1 caliban

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Posted 23 August 2002 - 02:28 AM


A few years ago, telomeres and telomerase were all the rage.
For many people, telomere technology was THE most promising venue in anti-aging research ever. Indeed many people only took the topic seriously because of telomere discoveries.

Now it has grown rather quiet about telomeres. Geron is turning away from the technology at least for the purpose of anti-aging research.

What do you think (and what evidence do you have) about the future of telomere applications?

Edited by XxDoubleHelixX, 27 May 2003 - 10:17 PM.


#2 Lazarus Long

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Posted 23 August 2002 - 03:40 AM

This is not telomers directly but it is a necessary technology for being able to identifiy and manipulate that specific element of the genome. If the claims of this company are borne out then they may hold the key to the methods for both the mapping and manipulation of the sequence, not just a specific gene.


Genicon brings its molecular-level methods to the research market. Genicon
Sciences and its venture capital investors are hoping that big things really
do come in little packages. The privately held San Diego biotechnology
company in July launched its first product - a way to analyze genes that
Genicon boasts is the first true nanotechnology to make it to the life
sciences market. Nanotechnology, the science of engineering at the molecular level, comes from the word nanometer - which is a billionth of a meter, the length of about five atoms. (SignOnSanDiego.com 8/16/02)

(excerpt) For Genicon and its backers, the prize is a potentially lucrative niche in the burgeoning business of microarrays. The use of microarrays, also known as DNA chips, has helped revolutionize the drug discovery process, allowing researchers to simultaneously analyze thousands of genes in a single experiment.

Microarrays also promise to be an important diagnostic tool for doctors, who one day may be able to use the technology to analyze a diseased cell's genetic fingerprint and determine which therapy is best for a patient.

What Genicon offers is a new way to "tag" and read a microarray, using chemically treated, nano-sized gold particles that bind to genes or other material in a sample.

When the microarray treated with the nanoparticles is exposed to white light, the genes of interest in an experiment essentially light up, allowing researchers to figure out such things as which genes are linked to a disease or how a drug interacts with a cell.

The technology, dubbed resonance light scattering, offers advantages over existing microarray detection systems, most of which are based on fluorescent dyes. Those dyes can be problematic; they aren't always precise or sensitive enough to pick up every gene, and can bleed together, resulting in false or inconsistent results.

Put in astronomical terms, fluorescent-based microarrays can detect the Milky Way, but Genicon's nano-based system can pick out individual stars, said Patrick J. Mallon, chief executive of Genicon.

"If you have a cancer cell that is expressing a gene, but only one in every 1,000 cancer cells are doing it, we can pick up that one in 1,000, where current technologies can't," Mallon said.

http://www.signonsan...9_1b16nano.html


This is only one of many approaches that are leading to the ablity to accomplish the goal of reprogramming for the genome. This will include telomeres. Knowing that something is functioning toward a purpose doesn't mean we fully understand how the process functions. Telomeres and frankly most of the "programing" of the genome is still undeciphered. The genome project finally has a rudimentary "map" of the areas of function and the pieces of what we do know are being stiched together.

BTW, I got this from the general news and Nanogirl's post. This is not an endorsement. I am only offering a perspective on the extent of supportive state of the art research and development.

Here is some more info:
http://www.genlink.w.../teldb/tel.html


What are Telomeres?

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Telomeres are the physical ends of linear eukaryotic chromosomes. They are specialized nucleoprotein complexes that have important functions, primarily in the protection, replication, and stabilization of the chromosome ends. In most organisms studied, telomeres contain lengthy stretches of tandemly repeated simple DNA sequences composed of a G- rich strand and a C-rich strand (called terminal repeats). These terminal repeats are highly conserved; in fact all vertebrates appear to have the same simple sequence repeat in telomeres: (TTAGGG)n. Often sequences adjacent to the telomeric repeats are highly polymorphic, are rich in DNA repetitive elements (termed subtelomeric repeats), and in some cases, genes have been found in the proterminal regions of chromosomes.


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#3 Lazarus Long

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Posted 23 August 2002 - 03:51 AM

Here is an interesting paper I found when I "Googled".



TELOMERE CANCER THEORY


BY
Robert D. Darby
In 1977, I wrote a paper on a genetic model for the cause of cancer. The paper was not published, but was distributed to a small group. In 1991, it was transferred to a word processing document. The introduction was updated, spelling was corrected elsewhere, several diagrams were redrawn with a plotter, but no other changes were made. Now it has been transferred to an HTML document and it is available at:

Cancer and the 16 Tissue Man
http://hood.hctc.com/~darby/PAPER.HTM

In the paper I was describing a counter mechanism for the cell's life span and how this counter can cause cancer. I described it as having a coding of CGT, (which we now know is wrong) and as an incremental counter. But, I did say the following in the paper:

"...it is identical in all tissues of the body. One of its primary functions is to control when a cell divides and how many times it will divide (or its life span). Unlocking the secrets of this gene indeed, is the secret to aging, the secret to immortality."

"...the CGT is the counter mechanism and its occurrence from tissue group to tissue group varies."

"...it may occur 100, 1000, or 10,000 times within a cell."

What I was describing is now known as the telomere -TTAGGG, a decremental counter controlling the number of cell divisions. Equally important, I described how the telomere subunit is involved in the initiation of cancer. In the paper I show that cancer is initiated by the mutation of the telomere subunit sequence. I have not seen a paper describing the disposition of the deleted telomere subunit(s). It probably has been done, but it needs to be rechecked.

I theorize that there is an enzyme I call the "Where To Go" (WTG) enzyme. After cell division WTG picks up or transcribes the released telomere subunit(s) and initiates normal cell functioning. If the telomere subunit is mutated then one of the following things may happen depending on the mutated sequence:

1.) The cell may die.

2.) An oncogene may be initialized, but is still under normal telomere counting.

3.) Embryonic growth may be initialized, but is still under normal telomere counting.

4.) Telomerase may be initialized.

With a corrupted subunit anything may be initialized. Someone with the facilities should create a string of labeled and non TTAGGG subunits and insert it in a living cell and observe the outcome when the labeled sequence becomes active. This is a lot of work as there are 4,095 possibilities.

A mutated telomere subunit is the loose cannon in the cell.

Best viewed and printed with Netscape Navigator

Personal Information

Contact: darby@hctc.comCopyright © 1977-2000 Robert D. Darby. All rights reserved.

****************************

It's only one of some twenty thousand available articles out there. Research hasn't borne too much fruit yet but it hasn't stopped either. Nevertheless those of us alive now will see little direct benefit from this technology except perhaps as it may be applied in an experiment like the one described above. Now those humans not yet borne... Dem kids goin' be lucky, but is this the subject no one wants to talk about? Designer kids.

#4 Lazarus Long

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Posted 23 August 2002 - 04:09 AM

A mutated telomere subunit is the loose cannon in the cell.

Best viewed and printed with Netscape Navigator


This is a wonderful example of a parsed expression. Run them together and it is totally false, but at least amusing. [roll]

#5 Lazarus Long

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Posted 26 August 2002 - 03:34 PM

Here is a very relevant article from the current Nature Magazine LL

http://www.nature.co.../020819-13.html

Life preserver floods cancers
Cancer cells let telomerase loose.

26 August 2002
HELEN PEARSON

Posted Image
Telomerase is usually only available when cells are dividing.
© SPL

Tumour cells are awash with a protein that extends their lives, researchers have found. The finding could have implications for new cancer drugs and stem-cell therapies.

The enzyme, called telomerase, prolongs the life of some cells by repairing the ends of DNA that otherwise fray each time a cell divides. Eroded DNA ultimately kills cells - cancer cells produce abnormal levels of telomerase so they can multiply at will.

Now Kathleen Collins of the University of California, Berkeley, and her team have discovered one way that the enzyme is normally kept in check. Healthy cells package telomerase into a sphere within the nucleus, she found1. Only when a cell divides, and chromosome ends need patching up, is it released.

In cancer cells, however, the team found that telomerase slops around freely. If scientists can work out how to re-cage the enzyme, "it would provide a therapeutic point of attack", says telomerase researcher Ron DePinho at Harvard Medical School in Boston.

Telomerase is thought to be important in around 80 per cent of cancers. Molecules that inhibit it are already being tested to fight certain tumours.

Everlasting life

Telomerase was once hailed as the key to everlasting life. "It was supposed to be the magic bullet," says Collins. Some hoped that telomerase injections - to repair the regions known as telomeres at the ends of chromosomes - would preserve cells and fend off old age.

That dream withered. Researchers found that telomerase is only active in certain rapidly dividing stem cells in skin, bone marrow and gut. People with a rare condition in which they lack enough telomerase develop defects in these tissues but do not otherwise age prematurely.

But 'telomerase therapy' could still have benefits - to top up the enzyme supply in exhausted stem cells and renew their ability to divide. For example, DePinho has shown that liver cirrhosis - which ends in liver failure after years of frantic cell turnover - is improved in mice by adding telomerase.

Ailing stem cells in the blood or immune system might also be pepped up to treat anaemia or HIV. "Huge swathes of the population could benefit from telomerase," says DePinho.

Parcelled up

By tagging telomerase with a fluorescent protein, Collins' team could watch it move around the cell. When normal cells' DNA was broken into pieces by radiation, cells quickly impounded free telomerase into a compartment called the nucleosome. This prevents it attaching ends onto the DNA and allows the correct repair mechanisms to mend the gap.

Collins suspects that her findings could influence biotech companies that are developing telomerase treatments. Therapies that add extra enzyme might not work unless they deliver it to the right part of the cell, she says.

But Calvin Harley, chief scientific officer of Californian biotech company Geron, disagrees. He argues that stem cells could partition the extra enzyme correctly.


References
Wong, J.M.Y., Kusdra, L. & Collins, K. Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Nature Cell Biology, Published online, doi:10.1038/ncb846 (2002).


© Nature News Service / Macmillan Magazines Ltd 2002

#6 Lazarus Long

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Posted 26 August 2002 - 04:07 PM

Here is a very valuable resource that I think may turn out to be a front page link for this forum. It is the Encyclopedia of Life Sciences. I would love to see a formalized relationship developed between what we are doing and what they are at some point. hint hint....
[roll]
This is the link to their homepage
http://www.els.net/e...essionid=public

Also here are the links to the two articles that I posted on the topic of Aging that refer to Telomers

http://www.nature.co...7/990527-1.html

http://www.nature.co...8/990318-8.html

LL

http://www.els.net/e...277135c8d3a4f7f

Telomeres in Cell Function: Cancer and Ageing

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Accepted for publication:March 2001

Mary-Lou Pardue
Gregory DeBaryshe Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

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Keywords: cancer and ageing chromosomes DNA replication telomeres telomerase

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Telomeres are dynamic structures that make up the ends of chromosomes. They have important roles in assuring that genetic material is divided equally when cells multiply, and it is thought that they may be involved in regulating cell division in human ageing and cancer.

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Introduction

The ends of chromosomes in the nuclei of all eukaryotic organisms are specialized structures called telomeres. Telomeres are composed of deoxyribonucleic acid (DNA) (with associated proteins). In every organism studied, telomeric DNA consists of long head-to-tail arrays of repeated DNA sequences; the exact nucleotide sequence of the repeat depends on the species of the organism carrying the chromosomes. The cell can compensate for DNA loss from chromosome ends by adding more copies of the repeats, although some cells appear to lose the ability to make such additions. Telomere-associated proteins are less well understood. We do not know how many such proteins there are, nor do we know what most of them do; they present some of the most important unsolved questions about telomeres. See also:Chromosomes: higher order organization;Telomeres

In addition to compensating for loss of terminal DNA, telomeres have several important jobs that we know about and probably others that we do not yet know. They do at least four jobs in all organisms:

1. As mentioned above, telomeres provide a mechanism to compensate for underreplication of the ends of linear DNA molecules.
2. They keep true chromosome ends from fusing with other chromosome ends or with broken chromosomes to make chimaeric chromosomes. Chimaeric chromosomes can wreak havoc at cell division.
3. They distinguish true chromosome ends from breaks in DNA. Unrepaired chromosome breaks will activate a checkpoint in the cell cycle, which causes that cell to stop dividing until the break can be rejoined, either correctly or incorrectly.
4. In some cells, telomeres control the positions of chromosomes within the nucleus.

Recently, telomeres have become of significant medical interest because there is evidence to associate them with both ageing and cancer in humans, although possibly not in other organisms. The evidence comes from several findings: See also:Ageing;Cancer cytogenetics

•Extreme shortening of telomeres causes cells to become senescent and lose the ability to divide.
•Telomeres in older people are shorter than telomeres in younger people, suggesting chromosomes gradually lose DNA from their ends.
•Early studies of telomerase, the enzyme that adds the DNA repeats to chromosome ends, failed to detect telomerase activity in normal human somatic, i.e. nongermline, cells but did find activity in tumour tissue. This suggested that telomerase activity ends sometime during embryonic development and, if restored in later life, could lead to uncontrolled cell growth and cancer.
These and other findings supported a model of telomerase as a kind of clock controlling life span. Because chromosome ends are not fully replicated by DNA polymerase, they shorten at each cell division unless active telomerase compensates for this loss (see below, Problem of replication). The model proposed that eventually this shortening would cause loss of important genes and cells would die. Reactivation of the inactive telomerase in somatic cells would stop loss from the chromosome end, producing immortality, a characteristic of cancerous cells. See also:Ageing genes: gerontogenes;Cancer

As we have learned more about telomeres, it has become clear that this simple model is wrong in several respects. Nevertheless, in humans, both ageing and cancer appear to be associated with changes in telomeres; a major goal of those who study telomeres is to understand why these changes occur and what they really mean. Telomeres in all organisms share some fundamental jobs and characteristics. They also have some important species-specific differences. These differences are important because species-specific differences have historically provided the major clues for unravelling these kinds of genetic mysteries; in fact, differences are so useful that geneticists have almost accepted as dogma the exhortation ‘cherish your exceptions’. See also:Chromosomes and cancer;Chromosome structure

Importance of Ends in DNA Replication and Chromosome Segregation

Eukaryotic organisms have much larger genomes than do bacteria and viruses. These large genomes present significant problems for complete replication of DNA and for its accurate distribution to daughter cells. Eukaryotes have evolved several strategies to cope with these problems. Their DNA is divided into multiple chromosomes, apparently to keep the molecules at a manageable size; nonetheless, most of these chromosomes are much larger than the single chromosome that contains the entire genome of the typical bacterium. Bacterial chromosomes are circular DNA molecules, whereas chromosomes of eukaryotes are linear DNA molecules. It is experimentally possible to form a circular chromosome in eukaryotes by forcing recombination between the ends of a linear chromosome; however, these circles have a strong tendency to be lost at cell division or to break open. It has been suggested that such large circles may become tangled during replication or cell division, whereas the smaller bacterial chromosomes can avoid these problems. See also:Evolution of genome organization;Eukaryotic chromosomes;Bacterial chromosome


Problem of replication

Dividing a genome into multiple linear molecules may make the DNA easier to handle, but it presents other problems. The first of these is the problem of completely replicating the ends of a linear DNA molecule during cell division (Figures 1 and 2).


Figure 1
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Posted Image

Building blocks of chromosomal DNA. DNA, deoxyribonucleic acid, is a molecule whose building blocks are four nucleotides. The DNA nucleotides (mononucleotides) are, themselves, formed by the chemical linking of one of four ‘bases’ (cytosine, thymine, adenine or guanine) to a modified 5-carbon sugar, b-D-2 deoxyribose (indicated by aqua pentagons with the carbon positions numbered in red). The sugar is modified by the replacement of the hydroxyl (OH-) group on the so-called 5' carbon (shown at the upper left end of the sugar molecule) by a phosphate (PO42-) group. These mononucleotides are linked to form unidirectional, polarized molecules of single-stranded DNA. This linkage takes place when the OH- on the 3' carbon of the sugar moiety is replaced by a phosphodiester bond to the 5' carbon on the next sugar of the linear molecule, as shown in the dinucleotide. The polymer grows by repeated linking of monomers to the 3'-OH on the chain of mononucleotides.


Figure 2
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Posted Image

DNA polymerase cannot completely replicate the end of linear DNA. This diagram illustrates the replication of the end of linear DNA in the absence of a special mechanism for end replication. The final stages of replication of one end of the chromosome are shown. Replication has initiated at an internal origin, and, for simplicity, is drawn as proceeding only to the right (dotted lines on the left indicate that most of the chromosome is not shown). The replication machinery moves toward the end of the chromosome but polymerization proceeds 5'®3' along each daughter strand. Base pairing makes paired strands antiparallel. Thus, one strand (the leading strand) can be synthesized continuously, 5'®3' while the opposite strand (the lagging strand) must be synthesized backwards in short fragments as the machinery moves along the chromosome. Parental DNA strands are blue, new DNA is aqua. DNA polymerase can initiate polymerization only if provided with a 3'-OH primer. The 3'-OH is supplied by short (usually 8–12 base pairs) RNA fragments (pink). When synthesis is completed, the RNA is removed, leaving gaps, which are filled by DNA polymerase, primed by the 3'-OH of the DNA upstream of the gap. Because the final gap on the lagging strand has no upstream 3'-OH, it cannot be filled and it will lack the last few nucleotides at its 5' end. Similarly, at the other end of the chromosome (not shown), the other daughter strand will also lack a few nucleotides at its 5' end.



DNA replication starts at many different sites (origins of replication) along each chromosome and is carried out by an enzyme called DNA polymerase. DNA polymerase will initiate DNA replication only after a primer molecule, a short piece of ribonucleic acid (RNA), is transcribed at an origin of replication. This RNA provides an ‘upstream’ hydroxyl (OH-) group to which DNA polymerase attaches the first nucleotide of the new DNA. (‘Upstream’ to ‘downstream’ defines the direction in which successive nucleotides are added by the polymerase. When DNA synthesis is complete, the RNA is degraded, leaving a short gap in the new strand at each origin of replication. Except for the gaps at the extreme ends of the chromosome, gaps are flanked on both ends by newly replicated DNA. The DNA on the upstream side of the gap provides a hydroxyl to prime synthesis to fill the gap. At the upstream end of each strand of a linear chromosome, removal of the terminal primer leaves a gap with no upstream attachment point, thus DNA polymerase cannot fill this final gap. See also:DNA replication;Eukaryotic replication origins and initiation of DNA replication;Eukaryotic DNA polymerases;Eukaryotic replication fork

After the chromosome is replicated, each of the two daughter DNA molecules will therefore have one strand that is a few nucleotides shorter than its mother strand. When the shorter strand is copied in the next round of replication, both strands of the double-stranded granddaughter will have lost those terminal nucleotides. Thus, without some compensating mechanism, replication would lead to slow but continual shortening of chromosomes. Organisms with linear chromosomes must have special mechanisms to prevent this progressive loss at each round of replication. Many bacteria avoid the problem of a gap at the end because, in their circular chromosome, every gap has upstream DNA to prime synthesis. See also:Bacterial replication fork: synthesis of lagging strand


Telomeres solve the problem of underreplication of chromosome ends
Eukaryotes are not the only organisms that have the problem of completely replicating linear DNA. Viruses, which also use linear DNA to carry their genetic information, have a number of seemingly simple ways to avoid leaving a gap when the last RNA primer is removed. For instance, adenoviruses use a protein covalently bound to the 5' nucleotide (Figure 1) of their DNA molecule to prime synthesis; parvoviruses have short palindromic sequences at the ends of their DNA. These palindromic sequences can fold back on themselves to prime DNA synthesis. These neat, tidy solutions are a contrast to the telomeres on eukaryotic chromosomes, which are much more dynamic and seem to require more of the cell’s resources. See also:Viral replication


Telomerase and reverse transcription
In summary, in eukaryotes, chromosomal telomeres are composed of long head-to-tail arrays of species-specific DNA repeats. In almost all cases, these repeats are produced by an enzyme called telomerase. The process is illustrated in Figures 3 and 4. See also:Chromosomes: noncoding DNA (including satellite DNA);Short DNA sequence repeats


Figure 3
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Posted Image

Telomerase compensates for DNA loss by underreplication. This diagram illustrates how telomerase compensates for loss of terminal nucleotides on linear DNA. The enzyme extends the parental strand by reverse transcription of sequence from an RNA template that is part of the enzyme. Each end has many repeats of this short sequence. These repeats can be replicated by DNA polymerase to make double-stranded DNA. Although this replication will result in loss of terminal sequence, as in Figure 1, the loss can be replaced by reverse transcription of telomerase RNA. Parental DNA is in dark blue, with telomerase repeats in lighter blue dashes. The new DNA strand is aqua and RNA primers are pink.



Figure 4
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Posted Image

Reverse transcription by telomerase and retrotransposons (relatives of retroviruses). This diagram compares the action of telomerase with that of the reverse transcriptases of retrotransposons. The catalytic subunit of telomerase and an unknown number of accessory proteins (all protein components are represented by the yellow area) associates with the chromosome end and base pair the 3' end of the template segment of its RNA component (red) with the last few terminal nucleotides of the last repeat on the chromosome. (The template segment is a stretch in the enzyme’s RNA that contains 1.2–1.9 copies of the sequence forming the organism’s telomeres. This segment is depicted by the letters in the RNA template. The figure shows the template from Tetrohymena, the first telomerase discovered.) Primed by the 3'-OH on the end of the upper DNA strand, the enzyme copies one complete repeat from its template and then moves to realign with the new end of the strand and repeat its action. Most retrotransposable elements (retroviruses and retrotransposons) insert themselves into the interior of the chromosome. However, in fruitflies (Drosophila), two different retrotransposons can be reverse transcribed directly on to the ends of the chromosomes, where they form a unique telomere structure. The reverse transcriptases of retrotransposable elements differ from telomerase in several ways, including: (1) they reverse transcribe the entire length of their RNA template (usually several thousands of nucleotides) rather than a short defined segment (usually 5–10 nucleotides) within their RNA component; and (2) they do not use base pairing to align their RNA template with the chromosome. The catalytic subunit of reverse transcriptase and possible associated proteins are yellow. The RNA template is red and only the 3' end is shown. A, C, G, and T represent the four free dNTP (deoxynucleotide triphosphate) derivatives of the bases adenine, cytosine, thymine or guanine.


Telomerase carries an RNA molecule that serves as a template for the repeat sequence in telomeric DNA. The enzyme uses the 3' hydroxyl (Figure 1) on the end of the chromosomal DNA as a primer. It aligns the portion of its RNA that contains the telomeric sequence (usually 5–10 nucleotides, depending on the species of organism) with the end of the DNA and copies this RNA into DNA attached to the chromosome. This process is known as reverse transcription and is analogous to the process used by retroviruses and retrotransposons to copy their RNA into DNA for insertion into chromosomes. The most notable difference is that telomerase copies only a small specific sequence from the middle of its RNA and then repeats the process to form a string of identical repeats. See also:Cellular RNAs: varied roles;Regulatory RNA

Reverse transcription of an RNA template is obviously a good way to replace a sequence that has been lost from the end. What is surprising is that organisms have so many copies of the repeats on the end of each chromosome. For example, human chromosomes in germline cells have about 15 000 base pairs of these repeats on each chromosome end. Chromosomes of the laboratory mouse, Mus musculus, have 10 times more telomeric DNA, although the closely related Mus spretus has telomeres of approximately the same length as human telomeres. All of these telomeres are much longer than necessary to protect the genes from loss by underreplication, providing telomerase is active when germ cells are made. Even if there were no new additions to these arrays, it would take several lifetimes of loss from the ends before important genes would be exposed. The excess telomere sequences are thought to be necessary for the other roles of telomeres. See also:Human chromosomes


Telomeres keep true ends from fusing and from activating cell cycle checkpoints
The realization that telomeres are something more than just ends of chromosomes came from work by two giants in the field of chromosome studies, Herman Muller and Barbara McClintock, both later Nobel Laureates. Muller studied the genetics of fruitflies (Drosophila) and showed that mutations could be produced by X-rays. Studying the products of radiation, he found that chromosomes could be broken and rejoined to delete small parts of the chromosome or to join the fragments in new ways, giving what geneticists now call deletions, inversions and translocations. Many of these aberrations required that a chromosome undergo at least two breaks and then rejoin in a different order. One striking finding concerned the behaviour of chromosome ends: every broken chromosome acquired a preexisting chromosome end. These ends had variable amounts of chromosomal material attached, but all were linked to broken chromosome pieces in the proper orientation. None of the chromosome fusions involved inserting an end interior to the fused product; nor did ends fuse together like beads on a string. Muller concluded that chromosome ends were special structures, which he called telomeres (‘end-parts’). These structures were found only at chromosome ends and acted like ‘caps’; furthermore, all chromosomes needed these end caps. See also:Muller, Hermann Joseph;McClintock, Barbara;DNA damage

McClintock studied broken chromosome ends in corn (maize). In elegant studies, she forced two chromosomes to recombine in a way that produced one chromosome with two centromeres (a dicentric chromosome). These chromosomes broke when the two centromeres tried to go to separate poles at cell division, forming a ‘bridge’. McClintock observed that the resulting broken ends fused with other broken ends to give new dicentric chromosomes. These new chromosomes then repeated the cycle, which she named the ‘bridge-breakage-fusion’ cycle. Without the telomeric ‘cap’, the chromosome ends were sticky, causing problems when the cell divided. McClintock studied bridge-breakage-fusion cycles in corn endosperm (corn kernels) but noted that these cycles stopped and chromosome ends ‘healed’ when the chromosome was passed into the sporophyte (the plant that grew from the kernel). See also:Chromosome rearrangements;Cell cycle

These cytogenetic studies preceded molecular studies of telomeres by nearly 40 yr but their conclusions are still valid, although today we have a better understanding of the underlying mechanisms. The results suggest that, in both animals and plants, telomeres have similar roles in protecting chromosome ends. Fusions of broken ends, like those found by McClintock, can be seen in both plant and animal cells. More recent findings shed new light on their cytogenetic results. For example, we now know that many cells have checkpoint mechanisms that stop them from moving through the cell cycle if they have a broken chromosome. This is thought to explain the failure to recover terminally deleted chromosomes in Muller’s experiments. In addition, we know that, when it is activated, telomerase can add telomere sequences to broken ends of chromosomes. This addition ‘heals’ the chromosome by providing a new telomere (however, the healed chromosome may have lost some genes if a piece of the chromosome was broken off). This is thought to explain the ‘healing’ that McClintock saw in the sporophyte. See also:Checkpoints in the cell cycle


Telomeres can direct the positioning of chromosomes within the nucleus
Organisms with multiple chromosomes face the problem of coordinating chromosome movement at each cell division. In mitotic divisions, each of the two daughter cells must get a complete set of chromosomes. Meiotic divisions that produce eggs and sperm present problems that are even more complex. In the first meiotic division, the number of chromosomes is halved and every gamete must get one member from each pair of homologous chromosomes. Accurate segregation of chromosomes is accomplished by pairing each chromosome with its homologue just before the first meiotic division and then segregating one member of each pair to each daughter cell. See also:Mitosis;Meiosis

Early cytologists noted that telomeres appeared to have a special role in the nucleus as the chromosomes prepared for the first meiotic division. During the time when each chromosome is pairing with its homologous partner, telomeres are closely associated with the nuclear membrane and gradually move to form a cluster on one side of the nucleus. The chromosomes stay arranged in this ‘bouquet’ configuration until after pairing is complete; they then lose their attachment to the nuclear membrane and move to the centre of the nucleus. The early observations could only be made on large chromosomes, such as those found in multicellular animals. Recently, high-resolution techniques have made it possible to study the same stage in fission yeast, Schizosaccharomyces pombe. Although distantly related to mammals and having a very small genome, this organism undergoes a very similar meiotic organization of its chromosomes, led by telomeres. The similarity between this organization in yeast and eukaryotes argues that this is a general solution to the complex problem of finding partner chromosomes in a crowded nucleus. In addition, mutations in genes coding for telomere-associated proteins in yeast disrupt this process, showing genetically that telomeres are involved in this process, as had been suggested by cytological observations on other organisms. See also:Chromosome mechanics

The involvement of telomeres in organizing the meiotic nucleus is readily apparent because these cells have distinctive morphology. It remains an open question whether telomeres have similar roles in other cell types.

Role of Telomeres in Ageing and Cancer

Telomere length and length regulation appear to be vitally important to the cell. Early experiments suggesting that telomere length is related to the ability of cells to proliferate has led to extensive study of telomeres in humans, mice and yeast. In all three organisms, there is experimental evidence that when telomeres become too short, a critical point is reached after which cell viability is rapidly lost.

In yeast, telomere length does not change with age. Telomeres in old cells are approximately the same length as those in younger cells. It has been possible to see the effect of telomere shortening by experimentally knocking out the gene that encodes the telomerase enzyme. When this is done, the telomeres gradually shorten. There is no obvious effect on the yeast until after many cell divisions. Telomeres become critically short after about 50 generations and cells die.

Human telomere length regulation is quite different from regulation in yeast. In humans, telomeres in most somatic cells shorten with age. These cell types do not have enough telomerase activity to maintain their original telomere length. As a result, telomeres shorten with each division. If human somatic cells are put into culture, they cease to divide after a number of divisions characteristic of the cell type. It is generally thought that division stops because their telomeres have shortened to the critical point. (The few cells that survive this crisis generally regain telomerase activity and become immortal.) We do not know how cells sense that the telomere length has become too short. See also:Cell senescence: in vitro;Somatic cell genetics;Primary cell cultures and immortal cell lines

It is thought that the downregulation of telomerase activity that occurs in many types of human cells may have evolved as a protection against the unregulated cell division of cancer. This suggestion is supported by evidence that telomerase has been reactivated in most tumour cells. Other support came from experiments in which active telomerase genes were put into cultured human cells. In the initial experiments, these added genes produced telomerase activity that made the cells immortal. This apparently straightforward experiment became more complex when more cell types were tested and not all responded positively. It appears that, while telomerase gives the cell the ability to expand telomeres, utilization of this ability depends on whether some, as yet unknown, number of other genes are active in the cell. Genes that are known to affect the outcome of telomerase activity include several already known to be involved in checkpoints that regulate movement through the cell cycle.

Further important information on telomeres has come from studies using mice in which the telomerase RNA gene had been knocked out. Their telomeres gradually shorten, but not until the sixth generation does the shortening produce dramatic effects in the mice. These effects are found in the testis and ovary, the blood-forming tissues and the immune system. It was not surprising that these tissues are affected: all undergo much cell division and would be expected to have undergone more telomere shortening than tissues where cells replicate less frequently; however, it was a great surprise that cells from these mice can develop into tumours even though they lack telomerase. It has been suggested that, because of their short life span, mice may not need the stringent control that humans have evolved to limit conversion to cancer cells. See also:Mouse knockouts

Clearly, we have more questions than answers about how telomeres affect cell ageing and cancer. Nevertheless, the evidence is that there is a significant connection and that study of telomeres will help us to understand these important problems of human health. See also:Ageing - future directions for research in the biology of ageing

Further Reading

de Lange T and DePinho RA (1999) Unlimited mileage from telomerase? Science 283: 947–949.

de Lange T and Jacks T (1999) For better or worse? Telomerase inhibition and cancer. Cell 98: 273–275.

Greider C (1998) Telomerase activity, cell proliferation, and cancer. Proceedings of the National Academy of Sciences of the USA 95: 90–92.

Pardue M-L and DeBaryshe PG (1999) Telomeres and telomerase: more than the end of the line. Chromosoma 108: 73–82.


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#7 Bruce Klein

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Posted 26 August 2002 - 04:59 PM

Laz said: Here is a very valuable resource that I think may turn out to be a front page link for this forum. It is the Encyclopedia of Life Sciences. I would love to see a formalized relationship developed between what we are doing and what they are at some point. hint hint....

Heh, I think we'll have to explore this, interesting idea.

#8 caliban

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Posted 26 August 2002 - 07:30 PM

hm.
a metacomment on this can be found here

anyway. now that those of us who did not know about telomeres are up to speed, ;)) can I reiterate my question?:

are telomeres still a worthwhile venue in anti-aging research?

Or to approach it from another angle:
As pointed out in the articles that Lazarus posted, telomeres nowadays are studied mainly in connection with cancer. Even GERON has dropped the anti-aging part and is concentrating on neoplasia - do you think that telomeres have more potential than that?

Personally I am still undecided on this. (that's why I am asking for your views)
I guess it depends to what extend you believe in the "biological clock" type theories and to what extend you are a wear- and tear person?

#9 Lazarus Long

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Posted 26 August 2002 - 10:16 PM

Yes Telomers are still a viable avenue in the anti-aging area but the return from investment wasn't realized as fast as promised. No surprise there.

As I tried to point out in the article about new gene mapping techniques they need a few more tools before they can rationally expect the manipulative result they seek.

Stopping Cancer will prolong life and give us greater control over the practical aspects of telomers in cell division but personnally I think that these techniques will provide the greatest benefits to the currently unborn whose DNA can be re-programmed with an Aging Clock that is quantitatively and qualitatively different than our own.

Patience, you expect miracles in a day and even Jehova took a week to create the Universe and even though a God, He had to rest all day on the Seventh. ;)

And I certainly hope that not only you and I are up to speed but any and all who subsequently read this. [roll]

Speaking about up to speed... What are you guys doing that embeds your links in text? I keep gettng the entire URL when I use the URL button above? [blink]

#10 caliban

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Posted 26 August 2002 - 11:20 PM

To Lazarus:
Well patience really is not one of my strong sides... please accept my apologies if sometimes impatience makes me inconsiderate. Thank you for posting your informative comments!! - I was just not expecting them. To do a URL either select the text you want as description, click on the "URL" code button and paste the address in there, or just click on the "URL" code button and paste first the address and then the description.


topic:

- telomeres might help against cancer. Thats good. But there might be more effective techniques?
- telomere techniques might enable future generations to live longer. Does not help you and me though. Gene therapy with telomeres is not very feasible in terms of risks and throughoutness.
- i agree with the tools bit. eg. telomeres might be helpful in (adult) stem cell or tissue engineering appliances. What sort of auxiliary techniques do you have in mind?

#11 Lazarus Long

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Posted 27 August 2002 - 01:05 AM

-Caliban says:
telomeres might help against cancer. Thats good. But there might be more effective techniques?


I hope there is a whole arsenal but telomers are interesting because the hope is to basically shut off the cancer's process of usurping the DNA usurpation that the mutagenisis causes. This is gene therapy by direct control over the transcriptase stage of the cell reproduction.

Caliban says:
- telomere techniques might enable future generations to live longer. Does not help you and me though. Gene therapy with telomeres is not very feasible in terms of risks and throughoutness.


Here I agree and basically said as much. Depending on your current age the options available to you for longevity will vary widely. I feel that those already 30 and above will get the best possible benefit from cybernetics until strong Nanogenetics is developed. B)

But if disease is diminished, and methods for fighting and preventing other diseases are developed from this approach then there is reason to continue the research. But Big Business R & D wants a faster turn around on investment and a more glamorous result. We may have to be satisfied with subtle causalities for a while. [hmm]


Caliban says:
- i agree with the tools bit. eg. telomeres might be helpful in (adult) stem cell or tissue engineering appliances. What sort of auxiliary techniques do you have in mind?


And this is the sixty four thousand dollar question. A paltry sum by today's standards but important nevertheless. ;)

I have to look closely at this but I wonder if there is an application that reverses the cancer methodology to use as an augmented antibody. A synthetically created one (introduced as a vaccine) that doesn't just try to match molecular shape so as to block receptor sites but as a universal vaccine that can adapt to the genetic signiture of any foreign microbe to disprupt its reproductive physiology cause it to lyse itself, instead having to be consumed by lymphocytes. [ph34r]

I do want to pursue this analysis. But wil return to it later. Speaking of published articles also there was a report published somewhere in the last few weeks from a number of the worlds scientists talking about aging and the changes that we should expect. It has also become the topic on such programs as NPR's Talk of the Nation as both the Science Friday edition and the socioeconomic and political analysis as well. We can't claim the credit for causing this discussion to finally start being openly aired but we are a contributing factor. [sleep]

I want to post that report when I find it because it details the probabilities associated with current age groups based on the likelyhood of medical advances and other technologies coming online to assist in prolonging life. I also would like to address some assumption I overheard in the talk I listened to about it. The contributors were physicians from over thiry different Institutes and Research Organizations.

Oh, BTW apology accepted and it isn't necessary to. I like getting an excuse for a well meaning strident RANT occassionally. No offense was taken anyway. :D

I'll take my passion over twenty complacent blaise pundants anyday. And what you were saying about telomers was too vague so I thought a little substantive learning was called for. Plus much of what I posted was HOT off the presses so it answered the question on "What is the state of the current research?" and gave us all the opportunity to share in the analysis. [roll]

You can return to your seat now ;) [ph34r]

#12 john

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Posted 04 September 2002 - 07:20 AM

GERON RENEGADE, TELE'S AND NEW INSERTION METHOD
About two or three months ago, a top Geron guy broke away and founded a company to explicitly work on telomerase and antiaging. I think his site is Sierrasci.com.
this is very very big news for the field.

Another news item, is a powerful technique to insert any gene into the adult animal....well, about one third of the cells. Let's hope they get better over time, and can remake the DNA of all of your cells. Using a nonviral vector, they claim to be able to insert any gene anywhere in the DNA. Even several genes. Tosk.com is the site. This method opens up hope for using info on age promoting and age stopping genes......we adults can get the bad genes stopped, and graft in the good antiaging genes. Plus, i think, getting the useful amount of telomerase genes where currently absent, once that useful level is determined.
There is a lot of hope in the air now.
John...back after an absence of several months...Hi everybody!

#13 Mind

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Posted 04 September 2002 - 03:37 PM

Quote From The Article Above

It is thought that the downregulation of telomerase activity that occurs in many types of human cells may have evolved as a protection against the unregulated cell division of cancer. This suggestion is supported by evidence that telomerase has been reactivated in most tumour cells. Other support came from experiments in which active telomerase genes were put into cultured human cells. In the initial experiments, these added genes produced telomerase activity that made the cells immortal. This apparently straightforward experiment became more complex when more cell types were tested and not all responded positively. It appears that, while telomerase gives the cell the ability to expand telomeres, utilization of this ability depends on whether some, as yet unknown, number of other genes are active in the cell. Genes that are known to affect the outcome of telomerase activity include several already known to be involved in checkpoints that regulate movement through the cell cycle.


From this it appears that telemorase is not a direct agent in the formation of cancer...just in the continuation of cancer cells. Written in 2001 and it still starts out with "It is thought that...". From what I have read, it seems as though telomerase should not be used as a magic bullet/blunt instrument (something I agree with...see influenza thread), but still plays a very important role in aging. It seems telomerase regulation/supplementation will be an important factor in anti-aging treatments once more is learned about its inter-relationship with other cell mechanisms.

Thanks for the great articles Lazarus.

#14 caliban

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Posted 04 September 2002 - 03:52 PM

Very interesting post, John!

It was about time that someone mentioned William Andrews name!

link to the company "Sierra Sciences" (dreadful name though)

Nonviral insertion is a very interessting tyopic as well. Does anyone have a clue what the TOSK people in particular are doing?

Links to the two conferences
http://www.knowledge...nts/6291207.htm
http://www.knowledge...nts/7171617.htm

#15 john

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Posted 05 September 2002 - 08:22 PM

Very interesting post, John!

hi Caliban, glad you liked the post.

Tosk, fm my brief survey of their site, is doing commercial service to labs,...lab sends gene, tosk does insertion into adult...poss also embryo ....rodents in ten days then sends the rodent out to the lab.

The tosk method is said to have been used in ...yeast?.....for over ten years. They have simply adapted it to mammals, it seems.

Since all readers of this list are nonembryos...I think.....lol...the insertion of desirable genes into adults is extremely consequential news for us. Insertion of blocking sequences to turn off bad genes is just as great a bit of news.

A tangential thought....If all the money now spent on fancy funerals were ....after cheap burial....sent instead to research on antiaging , think how that would speed real progress. Not likely to happen, but points up the foolishness of expensive funerals.
Regards to all, and glad to meet you Caliban. (About where are you located, Caliban? I am in New Orleans)

#16 john

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Posted 05 September 2002 - 08:36 PM

A few years ago, telomeres and telomerase were all the rage.
For many people, telomere technology was THE most promising venue in anti-aging research ever. Indeed many people only took the topic seriously because of telomere discoveries.

Now it has grown rather quiet about telomeres. Geron is turning away from the technology at least for the purpose of anti-aging research.

What do you think (and what evidence do you have) about the future of telomere applications?

JuveNews.com is an excellent source of news in the antiaging field, gaged to the pro and educated layman.
Probably all of you know of it, just thought some may not, as it is fairly new.
John

#17 Bruce Klein

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Posted 06 September 2002 - 04:55 PM

John,
Actually this is the first time I've seen JuveNews.com, thanks for providing the link. We're currently compiling a comprehensive Links Directory (find this on the home page). The main objective is to include high quality links.

#18 caliban

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Posted 06 September 2002 - 08:53 PM

lab sends gene, tosk does insertion into adult...poss also embryo ....rodents in ten days then sends the rodent out to the lab


yes that's what they say. What they don't say is how they actually do it. Anyone found material on that?

the insertion of desirable genes into adults is extremely consequential news for us.


Indeed. Sadly, regarding the dramatic failures early last year, viral Gene Therapy on humans is as good as dead it seems.



Off topic: (sorry I am terribly formalistic about this)



JuveNews.com : I signed up to the site about 2 weeks ago, but have not yet received a newsletter. Are they as good as they look? (my current favorite is Sageke )

John: Pleased to "meet" you too. I am based in Sheffield UK at the moment which sadly is not in quite throwing distance from N'Orleans

Links/BJ: Why can I only give between 5-9 points to vote for a link? Why not then only use a scale from 1-4?

#19 Lazarus Long

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Posted 08 September 2002 - 12:03 AM

BTW, Caliban sorry if I am not an omnicient Advisor (one with all the answers) but if the subject we are addressing were so easy there wouldn't be any need for an advisor. I think that we are still in the stage of assessing valid directions and sifting relevant questions from probable dead ends, so my comments on Telomeres were to get us all to keep thinking about what I consider to be still too nacent an area.

I also however think we should be looking closely at proteomes and RNA transcription. There are a number of aspects about aging that theoretically could be offset by carefully manipulating these processes.

As was pointed out, cancer turns the telomere production back on for the goal of producing more malignant tissue, not necessarilly the other way around. So if we come to understand better how cancer does this we could perhaps mimic that without allowing the functinal genetic usurpation of hte cancerous gene.

This is one example of an alternative approach that hasn't really had time to bear fruit even if there were a number of studiess already advancing in this area. But another is with RNA. If we could alter the "stage" that RNA recognizes from the DNA *clock* (so to speak) then we could trick RNA into producing cells in accord with an earlier period of development for the individual. Some of the mechanisms for tricking RNA may be with the subtle introduction of proteomes that make the DNA respond as if the organism were in an earlier phase of life and then begin cellular growth accordingly.

I realize that it would play havoc with our personalities to say, relive puberty, but this is not an irrational approach either.

Proteomes and Proteomics

Proteome Project

Proteome Mapping
(note this is a government website and access will cause the US Federal Government to track your interest. It is the Argonne National Laboratory)

Pursuing Proteomes

Again the problem is the nascent character of the understanding possessed by us of these new areas of genetic engineering. Proteomics holds a reasonable chance of reintegrating Telomeres for example into a theoretical model for longevity technology.

#20 Cyto

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Posted 15 September 2002 - 07:56 PM

I would have to side with the "wear and tear."

So there is full-length hTERT (human telomerase reverse transcriptase) protein and the hTR (human telomerase integral RNA). Both of these mainly make up the whole holoenzyme. But there are proteins such as: H/ACA proteins Nhp2p - Nop10p and Cbf5p, Staufen, L22, La. These are used to stabilize just the hTR. Overall the point is there is quite a few.

Now if you can extend the PDL (population doubling level) in a cell this provides a wider window for cellular disruption to happen resulting in a cancer. With the entire human genome open to disruption for a longer period of time just doesn't seem worth it to me.

Overall it would take making BOTH a constitutive hTERT and hTR on top of making a more fidelic DNA polymerase for correcting occurring DNA damage. Also gene therapy for these changes to be "set in stone" is still being perfected.

Or just have totipotent ESC that will give you the malubility you need along with a shorter window for cancers to set in.

Making a higher fidelic DNA polymerases is certainly something to look into after life extension.

Overall, life extension through telomerase invariant synthisis would open you up to collateral genetic disruption.


"Here's what happens when you die -- you sit in a box and get eaten by worms. I promise you that when you die, nothing cool happens."

#21 Bruce Klein

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Posted 15 September 2002 - 08:22 PM

Caliban Said:

Links/BJ: Why can I only give between 5-9 points to vote for a link? Why not then only use a scale from 1-4?


Ahh, yeh... the rating scale for links does seem a little backwards. I'll see if I can play around with that.

#22 fueki

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Posted 28 December 2002 - 07:13 PM

The immortality by telomerase is my life purpose and sense. Anybody agree? Contact me.

#23 Lazarus Long

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Posted 28 December 2002 - 08:36 PM

I think you can honestly recognize that we would all agree that there is much to be gained through the study of telomeres and the various ways to manipulate them.

What ideas are you proposing?

#24 Cyto

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Posted 28 December 2002 - 11:20 PM

And to be more specific.

How do you plan to make Transcription Coupled Repair(TC-NER) and Global Genomic Repair(GG-NER) more fidelic and responsive to counter the longer time frame of cells being open to 'genomic disruption?'

Would you 'create' another self-editing system?
Maybe model it off the XP family?

I am curious too as to how this could work in our favor.

#25 fueki

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Posted 29 December 2002 - 06:21 PM

look at my intro in open forum: http://www.imminst.o...ST&f=75&t=571

#26 Socrates

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Posted 04 January 2003 - 06:47 PM

The immortality by telomerase is my life purpose and sense. Anybody agree? Contact me.

Well, I think we are all here for the same reason, but what about if all these efforts aren't worthed? What if we will die anyway? What if immortality will be achieved no matter when but after our death? If so we should live also the moment day by day. We could also die tomorrow in a car accident... Huh?
Anyway how are we going to change the telomerase enzyme in all the cells of our body? I got an idea:
Using a virus?
Posted Image
Posted Image
That will change telomeres... in all DNA of all our cells
Posted Image
What do ya all think about it?
Is it feasable?

#27 Bruce Klein

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Posted 04 January 2003 - 08:54 PM

What if we will die anyway?

Socrates, Ever hear of cryonics?

#28 caliban

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Posted 04 January 2003 - 11:50 PM

As you point out Socrates, "Hope from Telomeres" is only viable for you and me in connection with some sort of gene therapy (be they viral or nonviral) or genetic tailoring.

The scenario that you are describing is certainly feasible, and has been used on humans successfully. (although not for Telomeres)
Trouble is, that you need to reach ALL cells in the body -including brain cells.
It is also not easy to warrant sufficient immunosupression- one boy died of such complications two years ago and gene therapy has been pretty dead in the water ever since.
There are also complications with cancer.

Germ line genetic modification of telomeres however could be a much more straightforward task- thus your offspring have a vastly increased life expectancy, while you might not.

Kindly discuss cryonics at the appropriate place.

#29 Lazarus Long

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Posted 05 January 2003 - 09:02 AM

Society for Neuroscience Annual Meeting,Florida
November, 2002

Cancer creates embryo
Cloning brain tumour overrides malignant mutations.

6 November 2002
HELEN PEARSON

Posted Image
Drugs that mimic cloning might one day help treat cancer
© SPL

Scientists have grown mouse embryos from cloned brain tumours, they revealed yesterday. The remarkable results imply that drugs that mimic cloning might one day help to treat the pernicious cancer.

Tom Curran of St Jude Children's Research Hospital in Memphis, Tennessee, performed the technique that delivered Dolly on a brain-tumour cell. With his colleague James Morgan, he injected the mouse cell's cancerous DNA into a healthy egg that had been stripped of its own nucleus.

Despite carrying malignant genetic mutations, the cloned cell grew into a small mouse embryo. "No one predicted it," Curran told the Society for Neuroscience's annual meeting in Orlando, Florida. Only when an abnormal gene failed to drive embryo growth did the mouse die, he thinks.

Some of the genetic changes that turn a healthy cell into a cancerous one must be erased during cloning, explains Curran, a process called reprogramming. These changes probably involve reversible chemical markers or structural changes in DNA that control which genes are active, rather than being mistakes in the genetic code itself.

The discovery suggests that drugs that help to reprogramme cells, and imitate cloning, might also help beat brain tumours. Some such therapies, such as histone deacetylase inhibitors, are already being developed to treat other cancers.



Embryonic tumour

Even without cloning, brain tumours share many characteristics of a growing embryo, the Orlando meeting heard. "There are intriguing trends," says cancer researcher Luis Parada of the University of Texas Southwestern Medical Center in Dallas.

Parada revealed that adult stem cells that sprout nervous system neurofibromas switch on and off many of the same genes as embryonic precursors to nerve cells. And Curran's team found that gene activity in medulloblastomas in the brain's cerebellum mirrors that in the growing tissue.

We'd all like to discover where the genes are and how they operate
Terry Van Dyke
University of North Carolina

Ultimately, scientists hope to work out the fatal sequence of events that converts a culprit stem cell into a budding cancer and find drugs that reverse or block it. Buried in the brain, such tumours remain the most insidious and mysterious of cancers; 100,000 are diagnosed annually in the United States alone, and most are incurable.

The recent creation of genetically modified mice with versions of the disease has fuelled the latest advances. Yesterday's special session at the annual neuroscience gathering was the first time cancer has been timetabled.

"We haven't come up with unified theories," says the creator of another tumour model, Terry Van Dyke of the University of North Carolina in Chapel Hill. "We'd all like to discover where the genes are and how they operate."

© Nature News Service / Macmillan Magazines Ltd 2002

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#30 Cyto

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Posted 05 January 2003 - 09:31 AM

Yes, I agree with cal on the cancer complications and the genes getting purged from cells. That is on top of the points I have already made.

EZ to Read List

[*] Opens genome to accumulate more 'errors' -very general term- "wear and tear"
[*] You would have to 'make' another 'repair' array like the two I present above.
[*] The gene therap. using virus promoters could cause cancer due to the random insertation. (Over-expression of gene(s).
[*] Did I also add that it could be a lifes work to try and make another repair gene array?

Sorry I just dont see this as time feasable.

now stem cells. . .




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