Telomerase

Since I took Cell Biology last year, the Telomerase Gene has been an object of curiosity to me. Manipulating this pathway could slow down aging. On the other hand, it could be used in the opposite way to fight cancer. I do understand that this raises the ethical issue of how much we are supposed to tamper with. Then again, tampering is what we do as scientists, climbing mountains because they're there.

I've been looking at this article for a paper I still haven't started for Biochemistry.

Is any one here doing work with telomere regulation? If so, I'd like to here about it.

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...how much we are supposed to tamper with.

Supposed by whom?

Discounting religious objections, how is there be substantial objection to this kind of technology?

hmmm. "here about it"

By Anonymous (not verified) on 11 Nov 2007 #permalink

My impression of this stuff is that the big questions are technical: how do you strike a balance between preventing cell death and preventing out of control cell proliferation (cancer)? The difficulty of that challenge is a good reason to doubt scientists will be giving us immortality any time soon.

Frankly, I'll be ticked-off if people DON'T work on this. I have high hopes for mankind's eventual ability to dramatically lengthen human lifespan, but it's not going to help me much if you are fretting about what some religious nut thinks about your efforts. Now get cracking-- I'm not getting any younger here!

The question you ask betrays one of the reasons scientists are always accused of extreme reductionism. The real answer is, before you allow the techies to resplice your telomerase to allow you to live longe,r you should get them to check which specific melange of dna repair gene alleles you have. Get it wrong and cancer will rise up and bite you. Oh and check those MHC genes too, elderly people die from communicable diseases too. Pneumonia anyone? or maybe a nice bout of MRSA or C. difficile?

If you can juggle that lot them I'm sure others can suggest yet more genes it is wise to have the right alleles for to avoid lethal or semi-lethal accidents. Also remember that just being alive is not enough, you have to be able to enjoy it. Which includes having all your faculties. The ancient Greeks knew that one, have we forgotten so easily?

By Peter Ashby (not verified) on 11 Nov 2007 #permalink

I do understand that this raises the ethical issue of how much we are supposed to tamper with.

So, vaccinations, antibiotics and by-pass operations are OK, but 'Thou shalt not tamper with telomeres'? This is new to me. Or do your unnamed sources demand that we outlaw all artificial interference with health, in order to go back to life expectancies in the range of, say twenties, maybe thirties? On the other hand, real immortality would be a problem, wouldn't it? Particularly immortality for many people. Just me and 6 or 7 others would be OK.

It was the word "supposed" that drew me to comment too. It does imply an intelligence that made the supposition before the opportunity arose for us to tamper. If you reword it as "is it wise for us to tamper" then I'm on board. Where are we going to put all the people if we extend our lifespans? How do we feed them? What about the other resources they will consume and the waste they will create? These are practical problems quite separate from any ethical issues.
Having said that, if we can do it, we will. Non homo sapiens, sed homo callidens.

By Lancelot Gobbo (not verified) on 12 Nov 2007 #permalink

I do understand that this raises the ethical issue of how much we are supposed to tamper with.

Yes, do we let the luddites and their fear of technology and change rule, or do we dare to fly? Do we remake our image, or do we let the religious attitudes of barbarians keep us weak and helpless?

It's funny, I'm reading a novel by Charles Sheffield called Aftermath where Telomerase treatment for cancer is one of the major subplots. Great minds, you and Sheffield. (There's also a group of religious nuts who want to take advantage of a global catastrophe to cleanse mankind of the unfaithful; I get the impression that Sheffield was none too happy with extreme faith)

No, we don't climb mountains because they're there. We climb mountains because we expect to have a better understanding of the world when we view it from the top ..

The word "tamper" implies that you're manipulating something not meant for you to change. Heck, MW defines it as "to try foolish or dangerous experiments".

The first step in not letting luddites and religious demagogues control you is to stop internalizing their worldview.

And your comment system requires javascript. :-(

If you extend lifespans without reducing the birthrate, you will increase the population. You have to ask the question, is this desirable, or sustainable? You will increase the dependency ratio and most likely reduce the per capita income, so you will have more people with lower standards of living (for everybody).

Not that I think we should stop researching, but you've got to weigh the consequences...

How would a CNS neuron be effected by modification of telomerase?

Mike Fox:
"How would a CNS neuron be effected by modification of telomerase?"

You probably wouldn't notice. Neurons are what we term terminally differentiated, iow they do not divide. Being a neuron is as far as they get. Brain tumours result from glial cells going wrong, not neurons. Whether this would affect conditions like Alzheimer's or Parkinson's that involve neuronal death is a moot point as we don't know the ultimate reason for the death in either case.

In short cells have to be dividing for telomere length to matter much.

By Peter Ashby (not verified) on 12 Nov 2007 #permalink

My (unexpected) reading late last night was the new issue of Discover magazine. There's an interview with Elizabeth Blackburn, known for her work on telomeres, starting on page 42. It might be of interest.

By W. Kevin Vicklund (not verified) on 12 Nov 2007 #permalink

I'm reading a novel by Charles Sheffield called Aftermath where Telomerase treatment for cancer

Quite so: for cancer, as opposed to against cancer.

All surviving cancers have a mutation that turns telomerase production on. Guess why.

By David Marjanović, OM (not verified) on 12 Nov 2007 #permalink

"Quite so: for cancer, as opposed to against cancer.

All surviving cancers have a mutation that turns telomerase production on. Guess why."

Not true, about 10% of cancers use the ALT method of extending telomere length, where they combine with sister chromatids to extend telomere length.

I do research on telomeres/telomerase and cancer, let me know if you have any specific questions.

A staggering variety of differentiated human cell lines have been immortalized in vitro by adding an active copy of the telomerase gene. I would expect increased oncogenesis, but according to one source that I remember seeing, but am too lazy to search for, incidence of in vitro cancer was not increased. This makes some sense, since telomeres help DNA resist some types of damage - you'd end up with DNA that's more durable against mutation, but that ought to be more cancer-prone if mutations actually occur. I'd like to hear that finding replicated before I'd bank on it, though.

I also dimly recall reading about rats or mice with overexpressed vs. eliminated telomerase. I think overexpression of T led to no observable changes. T knockout led to rapid aging in the second or third generation, but not the first. It turns out that rats/mice normally have longer telomeres than humans, and their longevity/cancer strategy differs from ours. Rats/mice generally die with lots of small but not life-threatening tumors. Our shorter telomeres lower the Hayflick limit ( one apoptosis threshold) giving us better initial cancer defense. In a small (fewer replicating cells, often short-lived) mammal, cancer isn't as much of a threat as in a large (more replicating cells, often longer-lived) mammal.

And double-check all that, 'cause it's not fresh in my mind.

By Spaulding (not verified) on 13 Nov 2007 #permalink

And yeah, I've seen mentions of telomerase knockout or interference used as a cancer-fighting strategy

By Spaulding (not verified) on 13 Nov 2007 #permalink

Clearly, manipulation of telomerase activity will result in increased human lifespan. However, it will no doubt result in rampant addiction to the regulatory agents. Side effects will include bluing of the sclera, and an inexplicable ability to tap into genetic memory. In extreme cases, this genetic memory can lead to a manifestation of future events...

By Charles Soto (not verified) on 13 Nov 2007 #permalink

I'm reading a novel by Charles Sheffield called Aftermath where Telomerase treatment for cancer

Quite so: for cancer, as opposed to against cancer.

All surviving cancers have a mutation that turns telomerase production on. Guess why.

By David Marjanović, OM (not verified) on 12 Nov 2007 #permalink