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#31 Cyto

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Posted 10 April 2005 - 11:45 AM

Yep, I'll be lurking at ImmInst 2005. Will be one of them life experiences I'd say [thumb].

#32 jrhall

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Posted 13 April 2005 - 01:09 AM

Every now and again I here that someone died and the cause was 'old-age'. I always wondered what that meant. I didn't think 'age' alone caused death, I thought you had to die because some bodily system failed, i.e. your heart stopped or kidneys shut-down or what ever. Is it something related to Hayflick's biological entropy? Does the body just collapse because so many parts are not working so well anymore?

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#33 Cyto

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Posted 13 April 2005 - 04:24 AM

Like you are saying, it is simply a general statement for something that has "worn out." I would feel wrong saying that its 100% 'normal' aging - toxins, such as alcohol and drugs ingested earlier in life could of contributed to the failure as well. And I can't ignore diet.

People will, of course, not point to this since the person is dead and we all have to be nice (roll eyes).

"Is it something related to Hayflick's biological entropy? Does the body just collapse because so many parts are not working so well anymore?"

(1st one) That contributes. (2nd one) Well, it depends on which one fails...I’ve seen a persons ability to swallow fail and that of course will have a snowball effect to it.

#34 DJS

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Posted 05 May 2005 - 04:11 PM

An issue I have begun to think about lately...

Question:

How would the aberrant program of menopause (which seems to be rather unique to the human species) affect our ability to implement SENS therapies on post-menopausal women?

Could this late acting program be indicative of other programs that are activated by the onset of a particular physiological state/ phenotype / level of accumulated damage?

Overall, I'm fairly confused on what the implications of something like menopause would have on the SENS proposal. Anyone care to provide some insights?

#35 John Schloendorn

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Posted 05 May 2005 - 10:50 PM

If we give the WILT part of SENS a go, or another form of massive cell replacement, then the "programmed" or "hormone" part of aging such as menopause might be rejuvenated (no total confidence here) by replacing the entire endocrine system with a young one.
The "diffuse" part of the endocrine system [1] can plausibly be replaced by replacing the epithelial stem cells from which they derive, and then gradually killing all wild-type epithelial cells. The brainy parts could be more difficult, but I'm not sure right now what exactly that would take and what not.
It could be that when one part of the endocrine system is replaced with young cells, the others (or its own hormones that are still circulating) will reset it back to old quickly. Thus, there could be potentially huge difficulties to get from gradual rejuvenation of single parts to systemic rejuvenation of the endocrine system.
It seems that a transient Conboy-like circulation experiment [2] would have the potential to overcome the hormone-part of the problem, but there could still be a locally mediated, non-circulation dependent part.

#36

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Posted 05 May 2005 - 11:38 PM

Excellent point Don. I am amazed that this has not been discussed before but menopause could very well represent the phenotype of a senescence switch that provides supporting evidence for a programmed theory of aging. As we know, unlike in male aging where the decline in endocrine function is gradual and difficult to isolate from a causative perspective, female aging is reproductively highly delineated. It would be valuable to monitor transcriptional changes around this time so that we can see which are the genes responsible.

From a SENS/WILT consideration I would assume that the periodic infusion of fresh (transcriptionally youthful) stem cells would replenish most degenerated tissues/organs and consequently return pre-senescence function. On the other hand, the anti-telomerase component of WILT may present some complications in respect to ova and their progenitors, but that is another issue.

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#37 John Schloendorn

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Posted 06 May 2005 - 02:57 AM

Then there is also the transplantation of hormone-secreting cells encapsulated in a semi-permeable membrane, which has shown some promise in order to take direct control of hormone aging [1]. Such transplants can evade the immune response and might also be shielded from other aspects of the systemic environment.

#38 DJS

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Posted 10 May 2005 - 04:14 PM

Thanks for the response guys.

A second question/idea...

There's lots of theoretical information in the biotech forum, but hardly anything on experimental techniques. (Of course, I'm sure there is lots of pertinent data scattered about, yet none of its seems to be centrally located.)

It also goes without saying that nothing beats hands on experience, but I still wouldn't mind having techniques unfamiliar to me like, say, crystallography, explained in detail. In my mind, I believe that one of the purposes of this forum should be to act as a kind of tutorial for the aspiring scientist. Do you think organizing a section that explains experimental techniques would be a good idea?

#39 John Schloendorn

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Posted 11 May 2005 - 02:30 AM

Hmm, not sure what you're having in mind there. Is it more like a forum that explicitely encourages asking experimental questions? Or would you just go ahead and pile up (or link to) any relevant protocols we can get our hands on, even before the questions are asked?
Let me in this context once more recommend the huge and fantastically hands-on oriented "methods in molecular biology" series. I think the "aspiring scientist" should be confronted with the need to do their own research in the primary literature as soon as humanly possible.

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Posted 11 May 2005 - 03:48 AM

I think theory must in principle be anchored to some basis of experimental evidence. Particularly when discussing prospective interventions, without sufficient knowledge of the diversity and limitations of the tools available to the molecular biology lab it diminishes the credible substance and may impact on the quality of readership and participation. If we are going to provide credence to the some of the lateral thinking in these forums it is important that what is proposed is counteweighed with a consideration of practical limitations. Therefore I think it's a terrific idea, but such a section should be strongly moderated and guided if it is to fulfil an educational and inspirational role.

#41 brokenportal

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Posted 21 May 2005 - 04:15 PM

What exactly is biotechnology?

#42 brokenportal

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Posted 21 May 2005 - 04:20 PM

Something Ive wondered for a while, I used to read alot about the brain and was left with questions like, if we have such sophisticated technology now days, why is science finding it so hard to pin point exactly what kinds of chemicals are flowing where in the brain, then measure them and give people the exact amount of chemical they need to help them with whatever problem they have?

The lack of being able to do this is one of the things that throws a little uninvited skepticism into my optimistic outlook on life extension. I mean, if we cant control and master whole molecules and compounds like brain chemicals, how can we hope to master something on an ever smaller scale like dna?

Its my hope that its like the old department of home land security, the departments are all scattered around, not working together, and being left on the back burner.

#43 brokenportal

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Posted 21 May 2005 - 10:26 PM

Does anybody know about how many gerontologists there are? and also all the surrounding figures, like interns, students, scientists who assist in gerontology, numbers in related fields, and any info of this sort.

#44 horehey

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Posted 21 May 2005 - 11:23 PM

i don't know anything about biology at all except for stuff i've read on this website. Quite a while ago I read some comment about how some reasearcher injected a persons heart with stem cells and the stem cells repaired the heart a certain percentage, i think it was somewhere between 10 and 20%. So my question is if you injected a persons heart with stem cells exactly the same way every year or so would that be enough to stop the heart from aging? And is their any reason why something similar couldn't be done to other organs? I'm sure even that is somehow extreemly complicated but is the basic idea behind what i'm thinking obviously flawed somehow? hopefully someone will read this thing and answer it, I had to go through the hassle of becoming a basic member just to ask it.

#45 John Schloendorn

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Posted 22 May 2005 - 01:41 AM

Brokenportal,

What exactly is biotechnology?

Hmm, tough one. I don't quite get the purpose of the question... Is it not enough to say "everything that is in a relevant way methodologically similar to what is being discussed in this sub-forum?"

why is science finding it so hard to pin point exactly what kinds of chemicals are flowing where in the brain

Because the flow is so insanely complicated. For example, it's much, much more complicated than the flow of electrons in the most sophisticated computer chip that has been built. It's in fact so immensely complicated that experts still disagree on just how complicated exactly it is. It's quite amazing that we're starting to manipulate it in any meaningful way nonetheless.

The lack of being able to do this is one of the things that throws a little uninvited skepticism into my optimistic outlook on life extension.

There are no grounds to be either optimistic or pessimistic, before you have studied this enough to get any conception of where we are, and where we're moving. So for now, all you can do is share the optimism or pessimism from the respective experts in the field. Important names in this sense are e.g. de Grey, Olshansky, Hayflick.

Its my hope that its like the old department of home land security

It is a bit like that, but that is not the only problem.

#46 John Schloendorn

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Posted 22 May 2005 - 01:47 AM

Horehey,
Hi, welcome to imminst. Yes, I believe your basic idea is sound enough to be pursued. I'm quite positive that this is how the first comprehensive rejuvenation therapies will work. (Although no one has actually tried the repeated injections you envision yet, or even measured the effect of single injections on aging.) You might enjoy reading my phd proposal, which outlines some details of that very strategy, as well as Ocsrazor's concerns for adopting the same strategy in certain brain regions.

#47 John Schloendorn

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Posted 22 May 2005 - 02:06 AM

Brokenportal,

Does anybody know about how many gerontologists there are?

That would depend strongly on the stringency of the term "gerontologists", so I'll just cover a few possibilities there. (Estimating senior scientists worldwide. Please be aware that these are subjective guesses and I might be proven wrong.)

Those who study aging:
Hundreds, but many are doing demographics, behavioral studies, sociology ect. that you might not find entirely relevant for our purpose.

Those who study aspects of the biology of aging (Biogerontologists):
Dozens. But the study of aging itself is not all that is necessary for rejuvenation (some say it does not matter much at all).

Those who reserach or develop anything that will quite likely be used in rejuvenation therapies (but they do it for the purpose of curing single or a few diseases):
Back to hundreds again, including cell replacement, gene therapy, tissue engineering, stuff like that.

Those who seek to combat age-related diseases in a way that cannot be expected to affect aging (i.e. the increasing probability of the same or other age-related diseases to occur):
Thousands, maybe tens of thousands.

Those who are purposefully trying to develop rejuvenation therapies:
A handful at most. (i guess that's what you call homeland security ;)

The typical research group in any of these fields has one or a few postdocs, several phd students, and up to a dozen students and technicians.
I cannot estimate corporate R+D.

#48

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Posted 22 May 2005 - 09:49 AM

Biotechnology by definition is the application of biological processes for industrial purposes such as the large scale production of hormones, beer ;) and antibiotics by microorganisms. In many cases the organisms are genetically modified to produce substances that they do not normally do such as the production of recombinant human growth hormone. The field is also concerned with such things as bioreactors (large scale fermentation devices), downstream processing (isolation and purification of the product) and most importantly the economics of these processes.

why is science finding it so hard to pin point exactly what kinds of chemicals are flowing where in the brain


Because the flow is so insanely complicated. For example, it's much, much more complicated than the flow of electrons in the most sophisticated computer chip that has been built. It's in fact so immensely complicated that experts still disagree on just how complicated exactly it is. It's quite amazing that we're starting to manipulate it in any meaningful way nonetheless.


I tend to disagree with John in respect to complexity. Whilst mammalian neurochemistry is complex, in my view we have a fairly good idea about the various neurotransmitters, their means of production their receptors and related mechanisms of their regulation. I would think that the internetwork topology of axons and dendrites is probably a great deal more complex as is the electrical signaling patterns that they carry. Neurochemistry is after all more related to the modulation of such electrical patterns.

#49 horehey

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Posted 23 May 2005 - 05:23 AM

John, I read your interests and it seems we think alike, i'll paste what i'm talking about:

Interests: Mainly cell replacement therapy. But I am also doing some aggregates removal work. (What more would it take, really?)

I've more or less given up on psychology, marketing, bioethics and the likes.


I believe that the cell replacement/aggregate removal combination is all it would take too, although like i said I don't really know anything about biology, I just think that method seems logical. (if by aggregate removal you mean removing old cancerous mutated cells) And specifically, the thing I agree most about what you said is that bioethics is a complete waste of time (i put what you wrote in my own words). I've tried to argue with people who were against stem cell research without any luck and after a while I realized there's no point in trying, now I basically just say "I really don't care what you think and this research is going to happen whether you like it or not." I hate how cristians, the president, ect. just ignore the significance of stem cells and act like they won't amount to anything. It seems like an "ignore it and hope it goes away" kind of mentality. I think this research is of such importance that it is a matter of national interest that we persue it. Although it might be nice to rip off the technology of Asian countries instead of the other way around for a change... Anyways I have another question that is more of a legal one than a biotech, but still important. Is research restricted to the few federally approved lines only federal research, or does that also apply to researchers with their own money? And is there any other kinds of limits on independent people, like a law against "cloning"? If either of these is the case then I don't see how any real progress can be made at all.

#50 John Schloendorn

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Posted 23 May 2005 - 07:31 AM

"Aggregates", or "junk" is a bit of an insider-acronym, referring to hard-to-degrade chemicals. During normal metabolism things go wrong sometimes, and very rarely some chemical results that cannot be degraded. These pile up with age and cause disease. See e.g. Aubrey's introduction over at SENS. In many cases it could be enough to replace the cells that contain the junk, but in other cases, if you kill the cells, the junk will be taken up by neighboring cells. Some types of junk are not in cells at all, but rather in the space between them. So you have to degrade some things in situ. We do this by searching for certain microbes that can eat them and steal their enzymes.
The killing of senescent and cancerous cells is a different part of the plan, i.e. the logical first half of cell replacement.
I share your feelings on certain proponents of what they call "bioethics". I "have given up" does not mean I would not enjoy the occasional conversation with a conservative. I'm just not trying to contribute anything new to the field, because the argument for life is really very simple and already made.
While many European countries have completely banned the derivation embryonic stem cells, the US are fine with privately funded embryonic stem cell resarch of any kind. But the administration is probably well aware that any private enterprise must ask itself "how long will that remain so?". So we are having a huge deterrent for any long to medium term investments.
And this is really how I see the US will defend its technological leadership. Once stem cell therapies become financially viable short-term investments, the money will simply flow and thereby create a setting in which even longer term projects have nothing to worry about. The government does delay the development with considerable success, but in the end no US government can sustain going against market pressures. So the priority of pro-embryonic stem cell activists would be to get the therapies economically viable asap.

#51 DJS

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Posted 23 May 2005 - 07:35 AM

Hi horehay,

Private and state funding of stem cell research is still permited in the US. For instance, in California Prop 71 was past during the last presidential election and allocated $10 billion to stem cell research in that state. New Jersey and other states have followed suit. What we are really seeing now is the circumvention of the obstructionist policies of the current administration by some of the US' more progressive forces. Bush&co will be reluctant to oppose state sponsored stem cell because the political costs could be quite high, but look for a real battle when SCNT comes close to being integrated in therapeutic applications.

I wouldn't disagree with you however that the policies of the current admistration are holding back progress, but I think that what ever road blocks they do put in the way will be insignificant, particularly on an international level.

#52 arobie

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Posted 25 May 2005 - 06:50 PM

I'm new to these boards, led here by lightowl in a discussion about Aubrey and SENS on the space.com forums. I've been lurking for a little while now, just reading through the threads. I don't have much to offer to the discussions; I'm not fluent in this subject matter, but I do have an interest...and questions. I quess the question that follows would belong here although it is more of a biology question instead of a biological technology question.

Dealing with reproduction and birth:

So far, we've only dealt with birth on Earth, in normal 1-g gravity. Would having gestation and birth occur in gravity lower than 1-g, such as 1/6-g or 1/3-g, be possible.

What problems would arise from this?

I'm not sure if this is the right place to ask this, and if it is not, I'm sorry. Please then lead me to where it belongs.

Thank you.

#53 Cyto

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Posted 26 May 2005 - 08:50 PM

If successful birth does occur in a micro-graviational environment I would expect the vestibular organ (motion sensory) to possibly atrophy if no stimulus has been provided for the child. And if one were to arrive at Earth then there could be a long term, or reoccurring, "Earth sickness" so-to-speak.

Also since there is no pull of gravity larger amounts of blood will actually reside around your head longer than normal. So your legs will look skinny and your head will look "puff." Course this brings into the question of if the "puffy" face of a child born in space is the real face or if the earth one would be...
Anyways, the lack of strain on the vasculature on the legs could be dangerous for a person arriving on earth for the first time since the pressure may cause too great a strain and lead to problems in that avenue (the heart would probably be in jeopardy if space-born). The "lack" of blood to a space-born would probably give them headaches as well.

And we can't forget the bone-loss. I really do wonder if the child would develop a common skeletal system in microgravity environments, course who is willing to do the experiment?


And you may find some of this stuff neat, they are a good read:

Microgravity and Immunity
http://205.149.6.147...nd_Immunity.pdf

Neocytolysis
http://205.149.6.147...eocytolysis.pdf

Microgravity Increases Virulence
http://205.149.6.147...icrogravity.pdf

Radiation and You...in space
http://science.nasa....19aug_blood.htm


Overall, I can't give you a study on children in space but I don't think its looking to good for a child in space. If we had engineered gravity that may be another story.

Edited by Bates, 26 May 2005 - 09:07 PM.


#54 Karomesis

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Posted 09 July 2005 - 06:27 PM

If progeria can cause the lifespan of people to be 15 years, is it possible the oppisite holds true? can one gene regulate lifespan on a massive scale and place our demise at 500 years? And/or can we genetically alter a group of genes to perform this purpose and achieve a primitive form of ENS?

Any specific genes in mind? Or possible mechanisms to turn on or off these genes?

#55 Mark Hamalainen

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Posted 09 July 2005 - 06:59 PM

breaking a complicated machine is much easier than improving it

#56 John Schloendorn

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Posted 13 July 2005 - 10:23 AM

But on the other hand, worms are complex machines, too.

#57 John Schloendorn

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Posted 13 July 2005 - 10:27 AM

At any rate, the first problem is that we can't just go ahead and "alter a group of genes" in an existing human being. This is the major technical problem for many SENS threads.

#58

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Posted 13 July 2005 - 11:15 AM

If progeria can cause the lifespan of people to be 15 years, is it possible the oppisite holds true? can one gene regulate lifespan on a massive scale and place our demise at 500 years?


Good question. On the surface it may stand to reason that if only one gene can result in such globally debilitating effects then it should be possible - with suitable engineering - that one gene should have a symmetrically positive effect. Taking this concept and extending it to groups of genes, it is known for example, that variations in the HLA cluster are responsible for more diseases in humans than any other region. My intuition suggests that there should be a small number of genes that could ultimately be responsible for most of the dysfunction that occurs during aging and consequently it should be the objective of the biogerontology community to isolate and re-engineer the expression of these genes. My advocacy of incorporating DNA repair in the SENS objectives has been driven somewhat on this premise. On the other hand my knowledge to date suggests that the cell has developed numerous competing layers of regulatory networks derived from coding and non-coding (rRNA) portions of the genome such that once a cell has undergone sufficient differentiation the web of these networks creates redundancies that prevent single gene modifications from enabling dramatic changes in cell fate. Differentiated cells, however, can be replaced from a stem cell pool meaning that we don't have to be too concerned with understanding how to modify them (so long as we know how to re-code progenitors in a stem cell pool).

So in my view, I would say that yes it is possible that the opposite holds true, that perhaps not one gene but only a small set of genes may have substantial lifespan enhancing effects - provided they are expressed at the right developmental stage.

#59 brokenportal

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Posted 16 August 2005 - 05:40 PM

Ive been looking for a good online science dictionary, one where I can look up things like IL-6 or TGF-B. Like that scientific B with the handle sticking down. How do you even look that up with out that symbol on your key board anyways? Does anybody know where the best free online dictionary like that is?

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#60 brokenportal

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Posted 16 August 2005 - 05:46 PM

John, thanks for the response on number of gerontologists. Ive been throwing those figures around in my head since you responded.

Now its developed into this question. How many gerontology scientists and other relevant scientists to the issue are out there who have the credentials to scrutinize SENS if they so chose to. Well, actually I should say, when they finally choose to.




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