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Telomerase Production Hormone
So you want a key to immortality, do you?
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Please note that I do know that aspects of this idea have been under discussion for years, in various places. But at least some of what is written here was independently thought up by myself.

At the end of each strand of DNA is an "end cap" called a "telomere". The main feature of a telomere is that it contains a number of repetitions of a particular sequence of base-pairs. The process of cell-division involves, as you know, copying all the data from existing DNA strands to new DNA strands. However, the actual mechanism for doing that copying is imperfect, and can't QUITE copy all the duplicate stuff in the telomeres. This is OK, because that is what the telomers are FOR! They exist to be partially sacrificed during cell-division, so that all the critical genetic code BETWEEN the end-cap telomeres is completely copied.

Well, in single-celled creatures, after cell division occurs, a certain enzyme, known as "telomerase", is produced that causes certain cellular machinery to get into action, to add some new duplicate base-pairs to the ends of the telomeres, replacing the portion lost during cell-division. Thus the final result is a cell that is as identical as possible to the parent cell, before division occurred. It is practically impossible to declare that one particular cell, that resulted from the division, IS the parent cell, while the other cell is simply "offspring". BOTH are offspring, and yet both are equal to the parent cell. Single-celled creatures are considered to be immortal, as a consequence.

Now, it happens that in multicellular animals, telomerase generally is NOT produced after cell-division. Each animal starts out with an initial length of telomeres at the ends of its strands of DNA, and after some number of cell-divisions, that length shrinks to the point of worthlessness. A cell usually stops dividing, grows old, and dies. Eventually the whole multicellular animal dies too, of course -- including humans.

There are two main exceptions. First, in the reproductive organs, cells are "singled out" to produce telomerase, to rebuild their telomeres, and to then divide into 4 half-cells, which become the sperm and egg cells necessary for the next generation. (I may have the details slightly mixed up, but the general notion is correct.) At least one genetic disease ("progeria", I think its called) is associated with the failure of the parent reproductive cells to rebuild the telomeres. Human children suffering from that disease usually die by age 12, of old age -- and LOOK old, too.

The second exception is called "cancer". Cancerous cells grow and divide, alarmingly continuously, practically forever -- and they can do that because cancerous cells do indeed produce the telomerase needed to rebuild telomeres after cell-division.

Because of the association of telomerase with cancer, there is/was considerable concern whether or not cancer can be caused by introducing telomerase into an ordinary multicellular organism. The experiments that I've read about, however, so far indicate that various test-animals have successfully rebuilt telomeres, restarted cell division, and become more youthful, WITHOUT developing cancer. I'm sure lots of other experiments are going on, about which I've heard nothing, so I won't claim that the final verdict on the matter is in.

With most of the background information now presented, only a little remains. Telomerase is one of those delicate enzymes that cannot be put into a pill and swallowed -- the digestive system will destroy it before it enters the bloodstream. However, telomerase is a natural cellular product, and cells are, individually, purely stimulus/response mechanisms....

Simply BECAUSE the production of telomerase by a cell can be turned on and off, there MUST exist a trigger-signal (maybe two, but an OFF signal is only needed if the ON signal is not time-limited). I will refer to that trigger as "Telomerase Production Hormone", because hormones are a general category of substances that a multicellular animal normally uses to tell specific parts of its body to begin producing various proteins (such as enzymes) for various purposes.

Immediately there is a bit of a conundrum involved here, because in Nature telomerase is an INTERNAL enzyme. INSIDE a cell is where ALL the production-triggers are located, with respect to the normal workings of telomerase. Inside the cell something triggers something that triggers something ... that triggers production of telomerase, which in turn triggers the rebuilding of the telomeres.

Nevertheless, telomerase itself, when located OUTSIDE a cell, can enter the cell and immediately begin triggering the rebuilding of telomeres. This implies that among all those OTHER triggers, we should be able to find something (which we can CALL, even if it isn't really, "Telomerase Production Hormone") that can also enter the cell, and set the process in motion. Depending on just how many triggers there are in the chain, we may even be able to find something we can put in a pill.


Vernon, Aug 17 2001

Telomerase and Cancer http://www.findarti...74/p1/article.jhtml
Relevant to preceding, dated 1999 [Vernon, Aug 17 2001, last modified Oct 06 2004]

General telomerase stuff http://resolution.c...omere/telomere.html
Relevant to annotations, page last updated 1998 [Vernon, Aug 17 2001, last modified Oct 06 2004]

Site devoted to Aging research http://www.arclab.org/
Last reference to telomerase dated 1999 [Vernon, Aug 17 2001, last modified Oct 06 2004]

Following genetic expression to the end of the trail http://www.ncbi.nlm...71398&dopt=Abstract
On the way to regenerative medicine [reensure, Aug 17 2001]

Alternative Recipe for Illmortality Now http://www.illumatron.com/
Resources for immortality via human cloning. [Qualien, Aug 17 2001, last modified Oct 06 2004]

metformin http://www.lef.org/...tml?GO.X=9\&GO.Y=10
Diabetes drug that increases mouse life span by 20% [pluterday, Oct 04 2004]

A current researcher! http://mcb.berkeley...y/BMB/collinsk.html
Well, well, various people are still studying it, and publishing. [Vernon, Oct 04 2004]

US Patent 6,686,159 http://patft.uspto....86159&RS=PN/6686159
Thanks, [acgt]! [Vernon, Oct 04 2004, last modified Oct 17 2006]

metformin http://www.lef.org/...tml?GO.X=9/&GO.Y=10
Diabetes drug that increases mouse life span by 20% [pluterday]

A current researcher! http://mcb.berkeley...y/BMB/collinsk.html
Well, well, various people are still studying it, and publishing. [Vernon, Oct 06 2004]


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       uh, yeah!   

       Your TPH is probably custard.

quarterbaker, Aug 17 2001
  

       waugsqueke, I agree. I HAVE noticed that the popular literature these days is almost suspiciously empty of any and all references to telomerase, so sometimes I wonder if the key hasn't already been found, and good old "they" don't want you to know. On the other hand, I haven't looked on the Web lately for any recent results....   

       Anyway, one of the things I was trying to point out here IS related to that "Better Dentition" post. With respect to telomerase, we need to learn more about existing genetic machinery. With respect to growing new teeth, we need to learn more about existing genetic machinery. This is NOT WIBNI stuff, especially since once we know the design of the NATURAL substance/key/trigger/hormone, we can use existing technology to tinker.   

       If, for example, all the triggers in the telomerase sequence involve delicate compounds, that can't be put into a pill, THEN we would begin studying exactly how those compounds are physically structured. In biochemistry, just about everything involves physical shapes interacting, even while chemicals also interact. HOW MUCH of the SHAPE of telomerase is really needed to trigger rebuilding of telomeres? HOW MUCH of the shape of any prior trigger is really needed? We can CRAFT molecules to desired shapes these days...and we can make those crafted molecules tough enough to survive digestion, too.

Vernon, Aug 17 2001
  

       There is an unusual degree of conservation between species for the telomere; its simple nucleotide order is identical in most species. The task of charging a cell with an expressive gene for the purpose of activating c-fos pathways or some other developmental tract seems easy. Most yeast artificial chromosomes owe their stability to the telomere acquired during cloning. Anti-aging researchers are speculating that the biological clock <grail> keeps time by telomere length reduction, and this may be true. Is a cell's loss of telomerase production the beginning of its demise? What of the concept of the cell as a system with multiple and potentially alternative pathways for development or expression--I've linked to one that is becoming better known, the GLI (a segment polarity gene) pathway to complete normal accurately expressed development.   

       The addition of telomerase to a cell will likely require a correctly expressed cell surface receptor, similar to steroid or ILGF receptors. You might otherwise need to design RNA that expresses its own receptor, substrate and antisense

reensure, Aug 17 2001
  

       This technology would be inferior to simply cloning (via nuclear transfer) yourself as a means to immortality.   

       As a result of years of jogging on hard surfaces, I have painful heel spurs. There is no reliable way to cure them. I can't jog anymore. Most people acquire these kinds of conditions as they age, and many are untreatable and incurable. I am fifty-three. What kinds of conditions could I expect my body to be beset by at the age of a hundred and fifty three? I already have a lot of crowns and fillings on and in my teeth, what shape will they be in in fifty years? Things will beset the 150-year-old which we've never even heard of now because no one keeps their body that long. Things like heel spurs, tooth problems, and so on are not necessarily related to aging but just to damage over time. I want a fresh, new body. My DNA can build me one.   

       In reality, I have probably already lost more than 90% of the memories I had acquired in my lifetime. What will be left of my memories of being 20 when I am 220 years old? Probably none.   

       I don't like the dreams I have recurringly of my childhood and youth. They are almost uniformly unpleasant. I have the same sorts of dreams of my youth which I had twenty years ago. If my aging were stopped, as a method of immortality, would I still be having those dreams a thousand years from now?   

       I don't want those dreams. I want new dreams.   

       At what point would a person stop aging? At eighteen? Twenty-five? Forty? How would you know you had chosen the best stopping time if you never experienced the later years? If you stop at age twenty-five, will you retain you biological urge to have children, forever raising successive waves of babies for eternity? And will your children do the same?   

       A life which never attains maturity is not a life but rather a life cut short.   

       A human life is a progression, characterized by development. To stop growing toward maturity is retardation, arrested development at best (it is the last thing I wanted to happen when I actually was young in years), and probably, in reality, would just be a form of death. To expect that your mind will grow toward maturity without your brain changing is foolisness.   

       Attaining immortality by simply stopping aging is a naive solution, it only sounds good until you really think about it.

Qualien, Aug 17 2001
  

       [Qualien]: // A life which never attains maturity is not a life but rather a life cut short. // clap…clap.   

       I have seen two disturbing cases recently that I feel deserve the full effort of the sciences in this regard. One, a victim of a mysterious infection caused by eating freshly killed bear meat that produced an irreversible quadriplegia. The other a horrible case of rheumatoid arthritis resulting from exposure to an unknown agent in the South American rain forest. Are scientists compelled to study cell processes and plan for treating these types of affilictions? I say yes. Longevity, as interesting as it is on its face, does not hold the fascination for me that it seems to for others. Maybe that will change; because, the older I get ...!

reensure, Aug 26 2001
  

       Qualien, I've been attempting to find the best way to disagree with you, since you wrote your annotation. I doubt that I've succeeded in finding it, so I'll say various things that I think need to be said, and hope you'll understand.   

       The WORST thing I wanted to say is this: When I first read what you wrote, I couldn't help thinking, "This guy is a stooge trying to cover up the telomerase breakthroughs in a 'snow job' of gobbledegook." I still wonder, but don't actively accuse you of it.   

       For evidence, however, there is that first line about cloning. You are somehow missing the distinction between doing something to make your DNA immortal, and doing something to make YOU immortal. A clone will not be you; it will be its own person. And we already know from Nature that all you have to do to encourage immortality of your DNA is to have a lot of offspring. Cloning is unnecessary! But to make YOU immortal, your body has to persist, not just your DNA.   

       So the main point of this reply is that you seem to have missed the essence of GROWTH that telomerase represents. You have spurs on your heels? With telomerase allowing cells to divide youthfully, you can have those spurs surgically removed, and you will heal just fine. Growth of new cells will ensure it! The same is true of cartilige cells, retinal cells, eyeball-lens cells, etcetera. Deterioration always sets in when cells stop dividing, and telomerase appears to be the answer to that. As for neural cells, they too are known to be able to divide, but usually don't after a certain point in Life. So deterioration of them and their capabilities is the consequence, and the solution once again is to restore their abitity to divide. Lost memories will probably remain lost, but new ones that last a longer time can probably be formed.   

       One aspect to Growth is that it can take place in a couple different ways. You could literally grow physically larger, for example. An advantage to that is you would gain a larger head, with room for lots more brand-new brain cells. A disadvantage is that you could only grow to 10 feet tall or so, before associated physical phenomena, like the Law of Gravity, or the Square-Cube Law, makes life precarious. But growth can be controlled; and many decades might pass before such growth becomes dangerous. By then such problems might be solved (move to Mars, maybe?), but if you don't make the effort to live to find out, you'll never have a chance to enjoy such solutions.   

       An alternate kind of Growth is "dynamic stability". Life in general is a dynamically stable series of a vast collection of chemical reactions. All sorts of deterioration are the results of breakdowns in the dynamic stability of Life; Growth can restore it. One does not have to give up maturity to avoid biophysical dilapidation.

Vernon, Oct 14 2001
  

       Does anybody know, what sort of DNA does telomerase lay down? How does it make sure it doesn't write a gene that codes for something poisonous? Does it all look the same, a predefined 'nothing pattern'?

sadie, Apr 25 2002
  

       sadie, telomerase doesn't create ordinary gene-coded DNA. Think about an average cassette tape, and the "leader" on each end of the tape. Ordinary DNA is like the data-holding main length of tape, while telomeres constitute the equivalent of "tape leader" -- and telomerase merely rebuilds lengths of "leader" that is lost during the imperfect cell-reproduction process.

Vernon, Apr 25 2002
  

       I APOLOGIZE   

       Someone left a message to which I wanted to reply, and somehow I wasn't paying close enough attention to the text under the link, when I clicked on Delete instead of Annotate.   

       Anyway, the gist of the message was something about being careful of side-effects of telomerase -- multicellular organisms stopped making it during growth, for some sort of evolutionarily sound reason, right?   

       Well, that certainly seems reasonable. Obviously cautious experimentation is in order. Nevertheless, it remains a fact that various cells in the body do tend to die, and replacing them is more-probably a good thing than not.   

       Telomerase merely ensures that accurate replacements can be produced. That "tape leader" analogy I mentioned in a prior annotation is a key notion: If some length of "leader" is lost after every cell-division, then after enough divisions, eventually actual DNA will be lost, as well. The resulting cells will by no means be as capable as before. And THAT is what telomerase can prevent.   

       Sure, it is normally thought that the cells that have run out of "leader" simply don't divide any more, and that may be the only thing preventing major systemic breakdown due to incomplete DNA duplication during cell-division. But as already mentioned, telomerase allows cells to rebuild their used-up telomeres (or "leader"), so that they can rejuvinate themselves via fission, rather than simply age to death.   

       So, as long as we avoid the "too much of a good thing is usually a bad thing" problem, I say that telomerase-production research should proceed.   

       Then there is the OTHER huge huge issue to tackle, should we successfuly increase lifespan by some enormous factor: What about the population explosion? That topic probably deserves its own thread here on the HalfBakery (and indeed there are a few out there already).

Vernon, Apr 25 2002
  

       I think the population explosion problem will be a non-issue, provided the use of any telomerase-based treatment is properly limited.   

       One could imagine that decreasing infant mortality rates would lead to higher populations. In fact, the opposite is true - if people (mothers) expect their children to survive they are more willing to use contraceptives.   

       The great benefit of telomerase isn't its extended lifespan. It's the extended youth - the slowing down of the damage that we happily call 'ageing'. If people expect to be young and fertile for longer, they'll be more willing to wait a few more years before having children.   

       Unless they're catholic, of course.

sadie, Apr 26 2002
  

       sadie, a longer reproductive period is more likely going to be true of men than of women. Women are born with a fixed number of eggs to ripen, and when they are all ripened and gone, the ovaries are empty. A woman could still be fully youthful in all respects, at age 200, but she isn't going to have any eggs left by then (probably not even by age 100, if she youthfully has regular menstrual cycles the whole time). SOME extension of a woman's fertility is likely, because I think that menopause normally tends to happen before all the ova have ripened. So a limited extension seems likely. Meanwhile guys manufacture sperm constantly, so if the guys are youthful, no matter what their age, so is their sperm.

Vernon, Apr 26 2002
  

       Actually, it doesn't matter if the fertile period really is longer - just that people *think* it is. If it has no effect whatsoever, that's even better, as more people will reach the end of their shelf life before they get round to reproducing. *evil grin*

sadie, Apr 26 2002
  

       Perhaps, sadie, perhaps. On the other hand, when women talk about their "biological clock ticking away", they are usually referring to the end of the reproductive years. A change in the definition of the last such year will not necessarily cause women to feel more carefree about the fact that their reproductive clocks are still ticking.

Vernon, Apr 26 2002
  

       One problem with this is that a key aspect of aging does not seem to be involved with telomerase. Many oldsters have sound bodies but become progressively demented. Brain neurons do not divide, and not because they lack telomerase.   

       Cancer and viral hijacking are the two big bugbears of multicellularity. There are many failsafe mechanisms to prevent a rogue cell from running amuck. Possibly we could do without telomerase and rely on the others. I'd like to see how the mice do first.

bungston, Mar 07 2003
  

       The recent hoopla (and lots of email spam) about Human Growth Hormone makes me wonder whether IT is one of the triggers for telomerase production... among the other things that that hormone may do.

Vernon, May 08 2003
  

       While waiting for the magic telomerase, I’ve started taking metformin (aka "Glucophage", used in the treatment of type II diabetes for 40 years now – see link) This has been shown, in rats, to produce similar longevity results to calorie restriction. I’ll let you know in 40 years if it works.

pluterday, May 08 2003
  

       I think that most people would probably be very satisfied with just having their lifespans doubled or tripled to about 200-300 years.Being immortal would get very tiring and boring after a while if you have had a chance to do everything you wanted to in life several times over and we might want to "move on" to something even more spectacular than our lives on Earth.On the other hand,it would be great to be young for a much longer period of time than we have now,especially if someone doesn't get to enjoy being young the first time around,if they had a difficult life during their youth and missed out on love or having a chance to go to university and do stuff that you need to be young to experience fully.In one of the other posts,someone raised to point of having children forever and creating overpopulation.I think that if we get to be advanced enough to stop aging,than we may be advanced enough to colonize other worlds.There are many thousands or maybe even millions of Earth like planets out there just waiting for us to explore and inhabit.Hopefully some potent anti aging breakthroughs are just around the corner,but with the lack of funding and ignorance of the topic with the public,it seems to be tediously slow!

Lew27, Jun 14 2003
  

       These techniques are in active development. For example see US Patent 6,686,159.

acgt, Aug 21 2004
  


 
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