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Author Topic:   Telomere Shortening.....
mark24
Member (Idle past 5195 days)
Posts: 3857
From: UK
Joined: 12-01-2001


Message 1 of 14 (34395)
03-14-2003 5:13 PM


Hi all,
Quick question. I can't think my way out of this, but I'm sure an answer exists. As we get older, that is, more cell divisions take place, our chromosomes get shorter. Why is it that poor ol' Dolly, now sadly deceased, had telomere lengths consistent with the sheep she was cloned from. Yet during meiosis, the telomere length is "reset" for a newborn?
How can I reset my telomere length, I've checked the manual, but, no joy? It can't be that hard, surely?
Thanks,
Mark
------------------
Occam's razor is not for shaving with.
[This message has been edited by mark24, 03-14-2003]

Replies to this message:
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 Message 5 by Karl, posted 03-18-2003 8:08 AM mark24 has replied
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Percy
Member
Posts: 22389
From: New Hampshire
Joined: 12-23-2000
Member Rating: 5.2


Message 2 of 14 (34403)
03-14-2003 6:13 PM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


Hi Mark!
Sorry, I can't answer your question, but if you're wondering about these kinds of things then you would just love the book The Experiment by John Darnton. It's fiction, but he did his research, including extensive interviews with leading scientists in the field, including one of the lead researchers on the Dolly team *before* Dolly was announced. It's a good read and it's chock full of interesting tidbits, particularly about cloning and telomeres.

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blitz77
Inactive Member


Message 3 of 14 (34443)
03-15-2003 2:46 AM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


There's an enzyme called telomerase which catalyses the lengthening of telomeres. The enzyme includes a molecule of RNA that serves as a template for new telomere segments. It is usually only present in germ line cells of multicellular organisms. Unfortunately, cancer cells also contain telomerase.
[This message has been edited by blitz77, 03-15-2003]

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Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 4 of 14 (34614)
03-18-2003 6:53 AM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


Microbiol Mol Biol Rev 2002 Sep;66(3):407-25, table of contents Related Articles, Links
Human telomerase and its regulation.
Cong YS, Wright WE, Shay JW.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA. Yu-Sheng.Cong@UTSouthwestern.edu
The telomere is a special functional complex at the end of linear eukaryotic chromosomes, consisting of tandem repeat DNA sequences and associated proteins. It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. The synthesis of telomeres is mainly achieved by the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase that adds telomeric DNA to telomeres. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. In humans, telomerase activity is tightly regulated during development and oncogenesis. The modulation of telomerase activity may therefore have important implications in antiaging and anticancer therapy. This review describes the currently known components of the telomerase complex and attempts to provide an update on the molecular mechanisms of human telomerase regulation.

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Karl
Inactive Member


Message 5 of 14 (34618)
03-18-2003 8:08 AM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


Mark - poor old Dolly didn't come from a meiotically derived zygote, if I understand the cloning process properly.

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mark24
Member (Idle past 5195 days)
Posts: 3857
From: UK
Joined: 12-01-2001


Message 6 of 14 (34619)
03-18-2003 8:14 AM
Reply to: Message 5 by Karl
03-18-2003 8:08 AM


Thanks for the replies.
So, if I'm understanding properly, telomerase is at work in the meiocytes tyat produce the gametes, & "restores" the chromosome length?
Mark
------------------
Occam's razor is not for shaving with.

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Quetzal
Member (Idle past 5871 days)
Posts: 3228
Joined: 01-09-2002


Message 7 of 14 (34621)
03-18-2003 8:32 AM
Reply to: Message 6 by mark24
03-18-2003 8:14 AM


Re: Thanks for the replies.
Well, yeah basically. Telomerase is a reverse transcriptase that uses RNA as a template for coding DNA segments. The whole thing revolves around repairing chromosomes, or at least the ends. Every time a chromosome replicates, the telomeres on the ends get shorter (apparently, at a point the shortness tells the cell to stop dividing) - IOW, this controls the "aging" of most cells. After x number of replications, the cells die. Cells with telomerase are essentially immortal. Germline cells, some single-cell eukaryotes, and some cancer cells manufacture telomerase.
All you need to do is figure out some way to develop an injectable, temporary telomerase gene into your existing chromosomes, and voila! Immortality.

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Randy
Member (Idle past 6247 days)
Posts: 420
From: Cincinnati OH USA
Joined: 07-19-2002


Message 8 of 14 (34622)
03-18-2003 8:45 AM
Reply to: Message 7 by Quetzal
03-18-2003 8:32 AM


Re: Thanks for the replies.
All you need to do is figure out some way to develop an injectable, temporary telomerase gene into your existing chromosomes, and voila! Immortality.
More likely instant cancer.
Randy

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Quetzal
Member (Idle past 5871 days)
Posts: 3228
Joined: 01-09-2002


Message 9 of 14 (34623)
03-18-2003 8:52 AM
Reply to: Message 8 by Randy
03-18-2003 8:45 AM


Cancer
That too. c-myc oncogene expression increases 70% in human cell cultures treated with a retroviral-carried telomerase gene. Hey, if it was easy, everybody be doing it...

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Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 10 of 14 (34668)
03-19-2003 7:58 AM
Reply to: Message 6 by mark24
03-18-2003 8:14 AM


Re: Thanks for the replies.
Dolly was cloned from an adult somatic cell. The nucleus was injected into an oocyte that was enucleated. It was then zapped with electricity to mimic the voltage change induced by fertilization when sperm penetrates the cell membrane (may be wrong on specifics since I studied repro biol about 15 years ago). Thus the telomeres of Dolly never had the chance to go through the maintanance process that would normally occur during oogenesis or spermatogenesis. If you clone a clone that already starts with chromosomes that are degraded i.e. take cells from Dolly right before she was euthanized and make clones they will start with an even shorter set of telomeres than Dolly had...keep re-iterating the process and soon you won't get viable clones.
If you want imortality (or at least to slow aging down) you need to control telomerase activity to maintain the chromosome ends, not just add to them uncontrolled. Otherwise, expect to have a nice constellation of cancer types in short order.

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Replies to this message:
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TrueCreation
Inactive Member


Message 11 of 14 (34976)
03-22-2003 8:32 PM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


Telomere & Telomerase Resources
Hey Mark, you might be interested in reading some material from the following site:
http://petunia.colorado.edu/~nakamut/telomere/
--Back when I had the interest in Genomics and bio-related I read up a little bit on the relationship between aging and the telomere, but that was ages ago..
-------------------

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Gzus
Inactive Member


Message 12 of 14 (35014)
03-23-2003 4:27 PM
Reply to: Message 1 by mark24
03-14-2003 5:13 PM


Stem cells may provide an answer
just freeze some of your cells when you're still young. Then, when you're older, clone them to make stem cells and replace worn out tissues, maybe even body parts. Either that or clone your body and get a head transplant.

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Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 13 of 14 (38149)
04-27-2003 11:44 AM
Reply to: Message 10 by Mammuthus
03-19-2003 7:58 AM


Re: Thanks for the replies.
While it is true that sheep and mice cloned through nuclear transfer have shown shortened telomeres compared to in vivo derived embryos this is by no means universal. Cows produced through NT actually have longer telomeres than in vivo derived embryos in some instances, it varies depending on the somatic tissue source.
See
Betts D, Bordignon V, Hill J, Winger Q, Westhusin M, Smith L, King W. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle.
Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1077-82.
Miyashita N, Shiga K, Yonai M, Kaneyama K, Kobayashi S, Kojima T, Goto Y, Kishi M, Aso H, Suzuki T, Sakaguchi M, Nagai T.
Remarkable differences in telomere lengths among cloned cattle derived from different cell types.
Biol Reprod. 2002 Jun;66(6):1649-55.

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Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 14 of 14 (38190)
04-28-2003 5:02 AM
Reply to: Message 13 by Wounded King
04-27-2003 11:44 AM


Re: Thanks for the replies.
Thanks for the references WK. Ease of cloning itself seems to be highly variable i.e. mice are easy but cats and dogs are more difficult. I am also not yet convinced that the telomere hypothesis of aging really plays such a causative role as some of its proponents suggest. Of course if the telomeres shorten to the point of knocking out genes that would be sub optimal. But does this happen in every cell? In enough cells to make a difference? Is it more importatn than loss of mtDNA function with age? Accumulation of DNA damage from exposure to oxygen radicals over time? However, it is interesting that telomerase can re-activate in some cancers suggesting a dedifferentiation of the specified cell types and re starting of the developmental process (at least in part).
I only have a minor side interest in cloning that derives from having had to debate groups that claimed mammoths would be cloned out of extinction from DNA extracted from fossils...which is pure nonsense.
Otherwise, I will just read whatever Ian Wilmut writes

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