Unlocking Cell Longevity: Understanding Telomere Extension

[bioquest]

How long could you make/lengthen the telomere of a cell?

 

[jim mcnamara]

Cells don't have a telomere, chromosomes do. Telomeres are special DNA sequences that are found at the end of a chromosome - important in the replication and stability of DNA molecules during mitosis and meiosis.

 

[bioquest]

Sorry...I don't know why I mentioned the word cell I know what a telomere is, I just didn't write down what I was thinking correctly..I had too many things in my mind at once lol

How long can a telomere be lengthened? Is my question

 

[MaWM]

There is an enzyme called telomerase which repairs the telomeres after a cell division. It doesn't lengthen them so much as maintain their size.

 

[jim mcnamara]

AFAIK there is no way to make telomeres longer. Ian probably has a more definitive answer.

Based on your previous posts, does this question have something to do with cell lifetimes or apoptosis?

 

[bioquest]

no not really, I mean I just realized I didn't know how long a telomere could be so I asked the question

 

[jim mcnamara]

The reason is some researchers have proposed that (hypothetically) shortening telomores would reult in increased DNA damage over time, lengthening them, less damage. ie., possibly greater cell longevity.

 

[MaWM]

The telomere protects the end of the DNA strand (maybe like those anglets on shoelaces? :) ). Some of the telomere is lost whenever the cell divides. Without a telomere, the part of the DNA that stores data begins to take damage.

 

[bioquest]

What's the maximum lifespan you think we could live using our knowledge of telomeres and why do you think that? I just keep reading people saying that you could live a really really long time using that technology

 

[MaWM]

Wow. That's really entering a world of unknowns. So.. let's speculate a bit here. Telomerase should prevent spontaneous cell deth through aging, and should greatly reduce DNA damage during mitosis. Let's ignore the dangers of cancer implied by use of temerase. So.. what's left?

Permanent damage to the body will still accumulate: broken bones that don't quite heal right, etc. DNA damage will still occur and be passed down to filial cells. If any cells become so damaged as to die, they will be replaced.. but you still have to be concerned with different parts of your body drifting genetically. It's hard to say what the results of this may be, but it seems like cancer would eventually be inevitable. Nerve cells will still not be replaced. Even assuming you don't develop Alzheimer's or other rapid degeneration, you should still find your metal faculties declining and your memory fading. Eventually, you may live 150 years but remember only 10 of them.

Bottomline. It's hard to say. People have a lot of pie in the sky notions about telomerase, but we don't really know what problems are unrelated to aging, which problems are related to aging, and which problems are prevented by aging (telomerase inhibition had to evolve for some reason). It's entirely possible that, once telomerase in given to humans to prevent aging, a whole panoply of new problems may be discovered.

 

[baywax]

AFAIK there is no way to make telomeres longer. Ian probably has a more definitive answer.

Based on your previous posts, does this question have something to do with cell lifetimes or apoptosis?

I was involved with a study on telemeres and their role in cancer. A cell that has had apoptosis turned off by a mutation is also known as a cancer cell. With apoptosis turned off (that is the p52 gene turned off) the telomeres of the chromosomes in that cell do not degenerate or rather they don't begin to lose information (ie: genes) like normal cells do when they age. This is why the cell can be called an "immortal" cell or... cancer cell.

There was an initiative to find a way to deplete the telomeres in cancer cells so that the cell would die or at least become useless in division (mitosis) and act less like a cancerous stem cell. This would be achieved and was achieved by introducing an "anti-telemerase".

To learn more about teleomeres and the people who have studied them you could check out "the story of teleomeres" in this compilation of abstracts and histories.

http://72.14.253.104/search?q=cache...res...+dr.+klingmann&hl=en&ct=clnk&cd=1&gl=ca

Find pp 30 to read a short history of the study of telomeres and the implications it has to do with aging and cancer.

 

[MichaelIASTA]

Telomeres

Geron is doing research into controlled Telomerase activation http://www.geron.com/showpage.asp?code=prodta for the purposes of rejuvenation
while simultaneously pursuing telomerase inhibition http://www.geron.com/showpage.asp?code=prodcati as a cancer treatment. Telomolecular Nanotechnology is using a different set of approaches http://www.telomolecular.com/nanocircles.asp and http://www.telomolecular.com/otrt.asp

As to your implied central question, technologies to lengthen telomeres will probably have a positive effect on lifespan but will not create the 500 year or 1,000 year life spans being touted by Michael Fossel or Aubrey de Grey. On the other hand, a comprehensive review of the literature on mtDNA, cloned and transplanted organs http://www.dailymail.co.uk/pages/li...Homepage&in_article_id=413551&in_page_id=1770
artificial organs http://www.med.umich.edu/opm/newspage/2002/artificiallung.htm etc. will lead the objective and critical intellect to the conclusion that mean, median and ultimate human lifespans will be increasing at somewhat more than the historical rate for the foreseeable future.

Regards,

Michael Ferguson

 

[yangxu]

Cancer cells have a breakage-fusion-bridge cycle involving absent/broken telomeres constantly being fused and broken apart at random, leading to improper chromosome segregation/replication during cell division, thereby giving these cells the ability to mutate and "evolve" rapidly.

 

[MichaelIASTA]

I am aware of this, though you should include links substantiating your assertions. While stimulated telomere lenghtening presents somewhat of a cancer risk, there are a number of other emerging technologies that show significant promise in defeating cancer. http://www.ihop-net.org/UniPub/iHOP/gs/94105.html In general, shortening of telomeres with age has been implicated in oncogenesis. http://www.nature.com/onc/journal/v23/n44/full/1207527a.html

Regards,

Michael Ferguson

 

[bioquest]

How much does telomerase reduce DNA damage during mitosis? and in what ways/to what areas of the body? (I know it wouldn't help with DNA damage in the brain)

 

[bioquest]

I mean based on this sentence my question is

The telomere protects the end of the DNA strand (maybe like those anglets on shoelaces? :) ). Some of the telomere is lost whenever the cell divides. Without a telomere, the part of the DNA that stores data begins to take damage.

could telomeres (theoretically) protect DNA from oxidative DNA damage, or does it only protect DNA when the cell replicates?

I had another question (Ignore all the ones other than these two? Although if you answer the other ones that still helps me) Does Oxygen get converted to free radicals inside of the brain at all? Thanks

Also would this be helpful? http://www.zealandpublishing.co.nz/CoQ10-Omega3.html Did it really extend animal life 56%?

The life extending quality of CoQ10 is also confirmed in animal studies. In an experiment repeated three times by Dr E. G. Bliznakov, mice given extra CoQ10 lived 56% longer than average.

Dr Bliznakov reports, "Equally fascinating was the fact that the quality of youthful life was maintained well into the animals’ extended life spans. They still had healthy glossy coats and little, or none of the expected signs of aging like patchy loss of fur, organ degeneration and lack of mobility."

In another experiment, this time by Dr E. G. Bliznakov, sedentary human volunteers were given 60 mg of CoQ10 for 8 weeks, with equally impressive results. He writes, "In this short time their hearts were able to display an increase in oxygen utilization and their maximal exercise loads improved dramatically. This improvement was achieved without additional exercise of any type." These results were not achievable using synthetic CoQ10, only using naturally fermented CoQ10.

Finally, if you have stem cells with original DNA, will they still turn into cells with DNA damage when put into an environment where there are only cells with DNA damage?

this post is the one where the questions are the most important to me..you can ignore all the other questions that would be okay but if you answer them that's also really nice..thanks

 

[bioquest]

So would you actually have perfect/flawless non wrinkled skin etc if you had maintained telomeres throughout your life? I thought they were factors other than telomere maintenance involved in skin thinning etc?
I heard there was prosthetic skin, but that can't be used as an alternative to our natural skin all over our bodies right?
Also I heard in China they were doing embryonic stem cell therapy; is it possible that if for example there was no immune system reaction they could completely regenerate an organ using as many embryonic stem cells as possible? why/why not?
Also when they hooked up the blood of an older mouse to a younger mouse, did it completely regenerate organs other than the liver/muscle, could it, if so which organs?
Also I heard they grew a heart using stem cells (outside of the body) in a lab could they do that with skin?

 

[bioquest]

never mind about the prosthetic skin question though...the only questions I wanted answers to were the answers in the post directly above this one...so if you answered those that would be cool

I meant, can they grow skin in vivo not in vitro (my friend said they could grow a heart in vivo?)
And also can the MRL mice regenerate their skin fully? (The strain of mice that can regenerate)

the post directly above this one and this post are the only questions that I wanted answers to..thanks

 

[bioquest]

please ignore all my questions other than the ones mentioned in this post here or elsewhere as I either got them answered or they ended up being irrelevant/kind of stupid questions. but I would really appreciate having the ones in this post answered.

The following questions are in regards to consistently having telomeres be the most beneficial length that it's possible to make them in regards to specifically having the best effect on reversing/preventing etc the aging of organs in each specific organ as a result of telomere maintenance gene therapy/protein manipulation. I don't know if anyone here knows this but could someone tell me the actual effect telomere maintenance (ie the form of that's the most likely to help with aged organs) had on aged/aging mouse organs specifically by answering the following questions? (these questions are in regards to the experiment where it would have had the most beneficial effect, or the experiment that somebody can determine the most that it most likely had the most beneficial effect, on an aging organ(s)) Did it completely reverse/prevent/anything the age of any of them (on the organ(s) that it helped with aging the most) (disregarding/pretending (when answering these questions) that the damage that was done from the gene therapy/telomere maintenance itself such as from the nanoparticles used to do the telomere gene therapy ie to replace a gene with a more active one, or to simply increase the amount of telomerase etc doesn't exist- just for the sake of answering the question since I am trying to think of the answer in a specific context) (and disregarding/pretending that there were no side effects like an increased risk of cancer etc from the telomere gene therapy just for the sake of answering the question since I'm trying to think of the answer in a specific context) or if not did it very much ie almost completely reverse/prevent/anything the aging of any of them? (on the organ(s) that it helped with aging the most) and tell me why that is your opinion/fact if possible? (especially since I want to make sure I don't get misinformation on this and confuse myself more) thanks for your time...I know there's some stuff not understand about telomeres...but can my questions in this post be answered 100%/how accurately?
Somebody somewhere said with telomere maintenance you would die with flawless skin (ie skin that's one 100% not affected by aging?) is that true?
Also when answering this if you think the effects would be different on humans by an amount that matters, please state how you think that the answers to my questions would be different if my question was about humans and not mice

* if the telomere maintenance would have the best effect from birth than keep that in mind when deciding which experiment(s) to use to answer my questions...even if that hasn't been done since it could be done if the experiment u're thinking of hasn't been done but you think it would be the one to answer my question with best given my requests then please state that it hasn't been done and just do your best to answer anyway. If the experiment that you're using to answer the question doesn't involve all the variables I want it to- ie having telomeres be the most beneficial length it's possible to make them in regards to aging- please note what it doesn't match in regards to what I wanted it to. Although obviously there can be unknown information; maybe just state what information is unknown if it's going to be in the answers to my questions (in this post)

Really really appreciate it

 

[bioquest]

basically the short version of my question is could/would altering telomere length theoretically completely reverse/prevent the aging of anyone or more organs...if anybody could answer that with 100% certainty/thereabouts that's the only question I want answered but it would also be nice to have the post right above this one replied to..thanks for your time

 

[baywax]

basically the short version of my question is could/would altering telomere length theoretically completely reverse/prevent the aging of anyone or more organs...if anybody could answer that with 100% certainty/thereabouts that's the only question I want answered but it would also be nice to have the post right above this one replied to..thanks for your time

The mutation that causes cancer also maintains the length of the telomere rather than letting it degenerate. This is part of the mutation's metabolic process, hanging on to the information found in the telomere of the chromosome. The result is, as I've mentioned, an "immortal cell". What seems to happen at this stage is that, after some time, these immortal cells are able to mimic the function of a stem cell and, upon metastasis, are able to produce differentiated tissues such as teeth and hair. This may or may not indicate the implications of "altering telomere length" artificially or otherwise. (edited for content)

 

[bioquest]

What other ways can telomere maintenance regenerate organs/make them younger etc other than by turning the cells into stem cells/using stem cells?

thanks, I really appreciate it

 

[Mike H]

Finding a way to selectively activate telomerase might do what you ask, as, in principle, some sort of gene therapy (which is still quite an experimental method itself). This is all speculation, as the issue of causality with respect to telomere shortening and aging is still on the table. That is, is the shortening of telomeres in some part responsible for aging, or is it a consequence of aging? While the general consensus is that it's likely the former, it's not been put to rest yet. It wouldn't be able to do anything about other forms of cellular damage, as things like reactive metabolites chewing up cell membranes and such is just biochemistry.

It's been suggested that there may be a trade-off between slowing aging and increasing one's vulnerability to cancer. One of the descriptions I remember about cancer is from my cell biology class - "it's basically when cells stop listening to one another and focus on propagating themselves." (Yes, a bit simplistic, but with an essential grain of truth.) If you give cells the means to keep dividing, you need to make sure they only respond when you want them to, such as in the case of tissue/organ damage or other unpleasantness. They need to stay in line the rest of the time, though.

There's a lot of literature in these areas, you may find it very interesting (especially as I'm no expert and hope I haven't totally misrepresented anything).

 

[baywax]

What other ways can telomere maintenance regenerate organs/make them younger etc other than by turning the cells into stem cells/using stem cells?

thanks, I really appreciate it

Telomere Therapy

http://www.google.ca/search?hl=en&q=Telomere+therapy&btnG=Google+Search&meta=

 

[bioquest]

Is it clear whether or not telomere maintenance could/would, or whether it definitely would not (if done in a way that didnt harm the person not sure if there is/could be such a way maybe with genetic advances) allow someone to live 150 years & why? (assuming there is no way to solve the oxidative dna damage problem although I guess overexpressing enzymes would help with that but cause other problems?) If so how long do you think it would allow someone at most to live & why? I thought I read that mice with it had barely aged organs but got cancer (But, disregard the cancer/increased risk of it when answering this question) thanks someone mentioned earlier here it could have you live 150 years but you'd get problems

 

[Mike H]

It's not clear to me, but I'm not terribly, intimately familiar with the literature. My impression is that there simply isn't enough hard data to provide any sort of reasonably firm answer to the questions you ask.

I would suggest following baywax's search link to see if anyone has done a more extensive review based on what is currently known.

 

[baywax]

Dr. P. Lansdorp is the person I worked with during the initial stages of research into telomeres and their relationship with cancer. This man was one of the first to begin this research.

Here is a complete list of research initiatives he has started... up to and including 2005.

http://www.bccrc.ca/tfl/pubs_plansdor.html

I remember a company was proposing to buy his research, back then, to use in the concoction of an anti-aging skin cream but it appears he has resisted the temptation... which would have been great... (to the tune of $300 million or so).

 

[bioquest]

Did Dr. Lansdorp come up with any ways to maintain telomeres or did he just work with cancer?

What ways is it possible to remove/delete genes, what ways is it possible to do that in an embryo, can it only be done in an embryo/why? (I thought that they took out the telomerase gene in mice and replaced it with a more active form of the gene but I don't know if they did it just in embryos)

 

[baywax]

Did Dr. Lansdorp come up with any ways to maintain telomeres or did he just work with cancer?

Try reading the research.