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What is actually being done?


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#1 manowater989

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Posted 20 June 2005 - 04:13 PM


Ok, I hope I'm not being too direct here, but I've read through many of the topics here and decided that I am concerned with precisely the same thing most of you seem to be. I realize that humanity has been seeking immortality since it could conceptualize death, I realize that any scientific breakthrough takes time and that this is probably the big momma of them all, I realize that you are discussing far-reaching implications while keeping a close watch on any upcoming developments, I do realize all of that. But I feel that I must inject a bit of kick-in-the-pants here. A call to arms perhaps, or at least a rush to action. Seriously, this is to any doctors, researchers, anyone like that. people who want to be activists, anyone? what is seriously being done about this, right now? I am sure that someone out there could, at this very minute, be trying to research ways of applying all that we've learned about the ways and reasons cells age, and all that we could learn, to actually trying to cure aging. I'm 18 right now, and I desperately do not want to die. Please, I want to know, what could be done within the next 50-odd years, what is being done right now? Something should be. I would appreciate anyone letting me know if they agree or disagree.

#2 Mark Hamalainen

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Posted 20 June 2005 - 05:23 PM

Go to pubmed.gov and search for 'stem cells', 'gene therapy', or 'tissue engineering'... there is a lot being done. True, there aren't any research labs specifically dedicated to cure human aging yet, but its coming. I myself am just getting starting on a career in research.

#3 manowater989

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Posted 20 June 2005 - 09:42 PM

Well, I did just that and the results did look....promising. Ok, so, you are just getting started in this career, that's also good. Is this particular problem among those you plan to try to tackle, and do you know of others in your field who are also going to be trying to solve this/ you would encourage to try to get on it? Let me ask you flat-out, and not to sound selfish, but: do you think that whatever you're doing now will be done in time to save someone who was 18 in 2005 (i.e right now) from getting old and ultimately dying of some age-related disease? I realize it's just an opinion, but I'm asking what you think: yes or no?

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#4 Jay the Avenger

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Posted 20 June 2005 - 10:35 PM

The Methuselah Mouse Prize, man. The most organized and solid plan to conquer the aging process.

www.mprize.org

And yeah, it will be in time. I really don't think solving this shit needs more than 3 decades.

In addition to the terms that osiris named, do some research to what nanotech can do for healthcare. There are plenty of options to make people healthier and healthier in the near future.

Think nano-sensors, personalized genome scanning/medication, personal healthmonitors, etc.

#5 Mark Hamalainen

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Posted 21 June 2005 - 01:45 AM

I'm currently 20, and I hope to benefit from life extension. However I am not as optimistic as Jay, I think we'll be pretty lucky to succeed in my lifetime. But I do believe there is a chance, which is why I'm working on it. The ~30 year timescale is very popular around here for some reason, and I think its pretty easy to demonstrate why that is overly optimistc. The same people saying 30 years now probably said 30 years 5 years ago. Also, the important time is not when we completely cure aging (which may a century away or more), but when we reach escape velocity [1].

[1] de Grey ADNJ. Escape velocity: why the prospect of extreme human life extension matters now. PLoS Biol 2004; 2(6):723-726. http://www.gen.cam.ac.uk/sens/CwM.pdf

#6 kevin

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Posted 21 June 2005 - 04:30 AM

Nothing like a good healthy fear of personal annhilation before you're too old and cynical to think anything can be done about it.

Osiris has pointed you in a few good directions. I think you will find as you do more research of your own that chances are very good (barring global catastrophe) that science will enable much longer life spans. The question is not "if" anymore, but when. Whether it is in time for someone of age "X" depends on many variables however. Many decades can be spent piddling around. It's very easy to watch the years go by when you're anaesthetized

If you are planning on getting into the research end of things, all the better, but the best form of activism, no matter what your profession, are the words you say in your day-to-day dealings with the people you come into contact with. Talking convincingly about the possibility with others is BAR NONE the most effective way of ensuring that it happens in time for you, and your loved ones.

Aubrey de Grey says there's a 50% chance of achieving 'robust human rejuvenation' fifteen years after it has been demonstrated to be possible in mice. The problem is we haven't even started with the mouse part yet and times-a-wastin'.

Your fear of death can be turned into something quite powerful should you wish to make it so.

Good to have you here.

#7 manowater989

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Posted 21 June 2005 - 04:58 AM

Well, you've given some interesting things to think about, to be sure. I'm not sure that I agree with all of them, but that's certainly ok. It's natural for people to doubt things until they actually come into being, the old "I'll believe it when I see it" attitude. I do sometimes talk to people about the idea, but I disagree that that's the most critical aspect. I think the most critical aspect is, in fact, the hard engineering work that needs to be done. I look at it kind of like spaceflight- it wasn't very long from Kitty Hawk to the moon, as is often famously stated. The basic, underlying principles are starting to be understood, with the decoding of the genome and all that, there's still some work to be done in that department, I could be wrong but I think that is mostly finished, the understanding of basically what causes aging on a general level. Now what they need to do is to figure out how to manipulate that, really dig deep into the specifics of precisely how the machinery works so they can change it, then from there it will be just fine-tuning. I don't know exactly how long that will take, obviously, but I should remind myself that when people who are 50 or 60 now were 18, the average lifespan was at least a little shorter, so young people now might have even a little longer than they think, and I do know about escape velocity and all that, I read about de Grey in Popular Science, and have been interested in immortality for much longer. I just hope that someone really gets to work on it NOW as opposed to later. It's like, for all the people trying to cure cancer for all this time, it's still not done yet. I bet it could be, though. I feel like I would like to give all of this a try, and see what I personally might be able to accomplish. Computers could have been invented a thousand years ago, the laws of physics haven't changed, it would have been possible. All it takes to create something new, in technological terms, is the knowledge of how the relevant properties function, and that doesn't necessarily have to happen on a timescale, it happens when someone figures it out, but in order for that to happen, someone has to be trying. The first big step I'd like to see, of course is, in this case, a mouse that doesn't just live exceptionally longer than the average for it's species (even 4 or 5 times longer) or delay old age for a long time, but one for whom it seems not to be coming at all, a basic change in biology that lets it live maybe 50, 100, or more times it's species' natural lifespan.

#8 kevin

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Posted 21 June 2005 - 05:12 AM

You are perfectly right about the hard engineering work that needs to be done, but before that comes funding for research and before that a recognition of need and possibility. If we take the need to do something about aging as 'read', although many people don't see aging as being a 'problem' which is a problem on its own, you still have to convince them that the chance is probable enough to justify the allocation of resources which they might otherwise have spent 'having fun' or put towards some other cause.

There is more than enough evidence existing to call into question the way people normally thing of aging as inevitable. Many people are working on the problem of age-related disease but there needs to be literally armies put to work on the problem in an effort comparable to the War on Cancer and then some. Where the rubber will hit the road however is when new biotechnologies allow people to live even only a little longer. Everyday that your loved one, or you yourself, has a quality of life that makes it worth living, is priceless, and even the technologies we see being applied today are beginning to make that difference.

Abiomed has an artificial heart that has allowed people given only 30 days to live up to an additional year and a half. Their 'new model' comes with a five year warranty and clinical trials for 4000 people are about to be announced by the FDA. If the optimism for this technology is borne out and the trials go well, can you imagine what the 800,000 people waiting for a heart transplant are going to think and the effect that having a completely artificial organ save an enormous number of lives is going to have on the way people think of technology extending life?

Things are going to get very interesting in the next few years on many fronts.

#9 marcus

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Posted 21 June 2005 - 06:48 PM

Manowater,

I agree with you that there is not a lot of focused research purely on SENS type anti-aginig initiatives, however, there is a great deal of work being done on technology platforms that will make implementing SENS much easier. Every advancement made in stem cell research and gene therapy is an advancement made towards eventually extending our health-span. All the labs working on gene therapy or stem cell therapy types of approaches towards treating specific disease states are in a round about way helping push forward our cause here. Take a lab working on utilizing stem cells to treat heart attack patients by replacing damaged cells with healthy cardiomyocytes. Their primary concern is to help people who have suffered heart attacks or have various forms of heart disease. But as a side effect we learn more about how stem cells interact in an in vivo environment. While we all lament that there is little direct research being done on true anti-aging therapies, there is a great deal to be learned by understanding what are some of the possible enabling technologies are and how they are being used today. Right now it is a matter of formulating which technology platforms have the best chance of being able to help us and then getting funding to try out those platforms towards treating aging as a disease. The key thing to remember is that the technology platforms are being improved upon and worked on every day.


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#10 manowater989

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Posted 22 June 2005 - 01:53 PM

Well, even be that as it may, ok, I'm of course glad that they are already working on the technologies that will one day allow for it, that is a great first step, but I wish, and I'm sure all of you agree, that they WOULD actually start applying what they're learning to SENS anti-aging research. Do you think we could try a letter-writing campaign (or something, that sounds kind of stupid, I allow) to get them to, or, better yet, are any of you who say you are going into the research field or are already in it GOING to actually start trying to work with this anytime soon?

#11 Mark Hamalainen

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Posted 22 June 2005 - 04:36 PM

Do you think we could try a letter-writing campaign (or something, that sounds kind of stupid, I allow) to get them


Who is them?

The research I am starting and will be doing is SENS oriented.

#12 manowater989

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Posted 22 June 2005 - 08:30 PM

Ya'know, the ubiquitous, mysterious, ill-clearly defined "They". Here, it refers to the research community in general, and, specifically, those pieces of it with the resources, essential experimental knowledge base and potential motivation to attempt to actively develop anti-aging stuff.

#13 eternaltraveler

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Posted 22 June 2005 - 09:42 PM

I think 20-50 years is a reasonable timescale for getting ourselves on the way to escape velocity. Quite frankly I think it could be done in a very short period of time if enough resources were pumped into the project, but most people think curing aging isn't a possibility at all. However far more are coming around. I notice that in my everyday life.

Luckily a lot of the problems that need to be solved aren't strictly about aging, and a lot of resources are being pumped into them anyway even if it isn't for the purpose of fighting aging directly.

Stem cells are being researched even if the current administration is holding it back in america, cancer is being researched in a big way. I'm of the opinion that those two things alone would be able to get you to escape velocity. Replace cells that wear out, and stop cancer which most of us would develop if we lived long enough. I don't think you need an all out WILT to get us into the "good enough for now" category with cancer either.

I think we have a little more time for all the rest of SENS (ablation of worthless cells, extracelluar crosslinks/junk, intracelluar junk, and moving the rest of the mito genome to the nucleus). Though many of these problems would likely be fixed on a similar timescale to the two primary concerns.

Developments like the artificial heart you mention Kevin could go a long way toward extending lifespan. Everyone's heart will go bad at some point. The only organ that we aren't going to be able to just swap out is the brain, and there is no reason we can't keep that chugging with stem cells.

I'm of the opinion we are on the mist of a biological revolution, all the pieces are there. The techniques have been delveloped, it really is just a matter of application (not to say that application isn't very difficult on it's own right).

#14 eternaltraveler

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Posted 22 June 2005 - 09:44 PM

(manowater989)

Ya'know, the ubiquitous, mysterious, ill-clearly defined "They". Here, it refers to the research community in general, and, specifically, those pieces of it with the resources, essential experimental knowledge base and potential motivation to attempt to actively develop anti-aging stuff.


Do what the rest of us here seem to be doing and become one of "them".

Edited by elrond, 23 June 2005 - 09:36 PM.


#15 DJS

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Posted 22 June 2005 - 10:07 PM

Stem cells are being researched even if the current administration is holding it back in america, cancer is being researched in a big way. I'm of the opinion that those two things alone would be able to get you to escape velocity. Replace cells that wear out, and stop cancer which most of us would develop if we lived long enough. I don't think you need an all out WILT to get us into the "good enough for now" category with cancer either.


Well we've been throwing billions of dollars at cancer for thirty years now with only moderately successful results. I'm personally pessimistic on cancer being "cured" anytime soon because the direction of the research is not addressing the underlying problem. Still though, nothing would make me happier than to see current research avenues pay dividends and make WILT unneccesary.

I think we have a little more time for all the rest of SENS (ablation of worthless cells, extracelluar crosslinks/junk, intracelluar junk, and moving the rest of the mito genome to the nucleus). Though many of these problems would likely be fixed on a similar timescale to the two primary concerns.


I think that getting rid of aggregates and crosslinks is important (and also much more realistically attainable in the short term). Both of these catagories deal with the "accumulation of damage" and simply rejuvinating the body with new pristine cells is not going to solve this problem. It would be like trying to clean a soiled toilet by filling it with more water. You need to flush first!

#16 kevin

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Posted 22 June 2005 - 11:08 PM

Well we've been throwing billions of dollars at cancer for thirty years now with only moderately successful results.


Don,

I'm sure you are aware that for most of the thirty years you refer to, researchers were using abacuses and chisels compared to some of the technology available to labs today. Extrapolating successes based on anything but the last five years or so, indicate a sharp uptick in progress against cancer. I seem to remember there being something like 150 new therapies slated to emerge over the coming few years.

There are high-throughput technologies being developed to define how stem cells differentiate (and how normal cells dedifferentiate). I think many of our predictions may be on the pessimistic side sometimes and the flower of human intellect is opening, faster than we think.

#17 DJS

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Posted 23 June 2005 - 12:18 AM

Kevin

I'm sure you are aware that for most of the thirty years you refer to, researchers were using abacuses and chisels compared to some of the technology available to labs today. Extrapolating successes based on anything but the last five years or so, indicate a sharp uptick in progress against cancer. I seem to remember there being something like 150 new therapies slated to emerge over the coming few years


Good point Kev, I was just trying to drive home the immensity of the problem. However, I really don't see a cure in the works with any of the near term treatments being developed (and yes, I have actually familiarized myself with cancer research so I have at least some level of understanding in this field). Most of the experts that I've read would agree with this statement. The real problem with all therapies currently available is that they are attempting to treat cancer after the fact. What is really needed is a bioengineering solution that prevents cancer from happening in the first place. WILT is one example, but I'm hopeful that other proposals will come along in the near future.

There are high-throughput technologies being developed to define how stem cells differentiate (and how normal cells dedifferentiate). I think many of our predictions may be on the pessimistic side sometimes and the flower of human intellect is opening, faster than we think.


Ah, a breath of fresh air...some optimism for a change! I've been reading too many doomsayers lately and the effect is that my mood has become rather gloomy. I sure hope you're right Kevin.

#18 manowater989

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Posted 23 June 2005 - 02:08 PM

Hmm....I actually have another related question. What EXACTLY were all of de Grey's Seven Deadly Sins, and what was the proposed fix for each? How much of those fixes rely on theoretical technology that doesn't exist yet, and how much of that is deeply in the works? Is he claiming that ALL we have to do to escape death is to keep up with maintenance of those 7 things? Exactly what form would the treatments take, and how effective would they be? I don't know, I've heard a lot of good arguments on all sides, and of course none of us can really know for certain what the future will bring, but still we keep on trying this crystal ball-gazing prediction game. I'd give almost anything to know exactly "when", "will it be in time", but I guess all we can really do....is guess.

#19 Mark Hamalainen

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Posted 23 June 2005 - 09:32 PM

You should read through the SENS site and de Grey's publications before asking us to restate it all for him. Afterwards I'll be happy to help you with specific questions.

#20 eternaltraveler

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Posted 23 June 2005 - 09:40 PM

(Don)

I think that getting rid of aggregates and crosslinks is important (and also much more realistically attainable in the short term). Both of these catagories deal with the "accumulation of damage" and simply rejuvinating the body with new pristine cells is not going to solve this problem. It would be like trying to clean a soiled toilet by filling it with more water. You need to flush first!


Don't get me wrong Don, I completely agree with you here. I'm just of the opinion that stem cells alone would allow us to "linger on" until other therapies are available. I do however believe this to be a moot point as the therapies you hint at above will likely be developed alongside or even before a fresh cell delivery system.

#21 eternaltraveler

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Posted 23 June 2005 - 09:44 PM

The site detailing SENS is located here: http://www.gen.cam.ac.uk/sens/ in case you couldn't find it.

#22 manowater989

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Posted 23 June 2005 - 10:27 PM

Osiris, would you mind giving the address of the SENS site? I didn't find it among this site's link section...

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#23 Mark Hamalainen

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Posted 23 June 2005 - 10:53 PM

Looks like Elrond beat me to it

#24 manowater989

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Posted 24 June 2005 - 01:08 AM

Ok, thanks guys. This is encouraging stuff....

#25 Michael

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Posted 24 June 2005 - 02:21 AM

All:

manowater989: I'm of course glad that they are already working on the technologies that will one day allow for it, that is a great first step, but I wish, and I'm sure all of you agree, that they WOULD actually start applying what they're learning to SENS anti-aging research. Do you think we could try a letter-writing campaign (or something, that sounds kind of stupid, I allow) to get them to

The first thing, again, is to create public awareness and an incentive system to break the logjam that is impeding work on serious anti-aging medicine. There are many other things you can do to bring radical anti-aging medicine closer listed on Aubrey de Grey's website; additionally:

manowater989:
Do you think we could try a letter-writing campaign (or something, that sounds kind of stupid, I allow) to get them

I firmly agree. It would be very helpful if people -- especially Americans -- would write totheir representatives directly for more funding for research on the biology of aging: currently, the National Institute on Aging blows 50% of its budget on Alzheimer's disease, and much of the rest of it on geriatric medicine or social gerontology -- which are important for improving quality of life in the biologically old, but are basically defeatist, palliative efforts, instead of the important work of intervention in the aging process itself.

Osiris: Who is them?

"They" would include your Representative and your Senator (or, in your case, Osiris: yourMember of Parliament (MP) and Senators, although American politicians have more money and an established research institution at their disposal).

Especially important for specific issues are members of House and Senate Committees, to whom you should write on specific issues of concern irrespective of whether they are your local representatives.

You can check out relevant lobbying organizations for ideas on issues that need your attention. For instance, on stem cell research, check out the Coalition for the Advancement of Medical Research (CAMR). Also, an excellent page of resources for advocacy targeted toward life extension issues is up at the Longevity Meme. You can also financially support these organizations, who will lobby and raise public awareness on the issues on your behalf.

You can also help to simply bypass Bush's embryonic stem cell "ban" at the state level: California's Proposition 71 was a great example, and many states now have similar initiatives, which could benefit from your support; Californian efforts to improve CO2 emissions standards for vehicles in the face of Federal inaction on the CAFE standards are similarly important. Cf these state programs on energy efficiency and climate change, in the face of the Bush administration's continued inaction and obscurantism on the issues.

And, at the end of the day: when elections come around, get out and vote.

Take heart. There is LOTS for you to do, even if you aren't planning a career in science.

Elrond: Stem cells are being researched even if the current administration is holding it back in america, cancer is being researched in a big way. I'm of the opinion that those two things alone would be able to get you to escape velocity ... I think we have a little more time for all the rest of SENS

I really don't think that this is likely. Most of us assume that cures for major diseases, such as those likely treatable to some extent via the above, wold lead to dramatic increases in life expectancy, but 'taint so: the av'g person's longevity gain from the utter ERADICATION of cancer from human experience would be <=3.2 years of life. Ischemic heart disease? <=3.55 years. Both together ("if one doesn't get you, the other will")? <= 7.83 years. Both, plus all circulatory diseases and diabetes? 15.3 years (1).

Stem cells will help treat and in part cure many diseases, but clearly will not alone be a complete cure for much age-related disease: eg, Alzheimer's patients ultimately need new neurons to replace the ones utterly destroyed by the disease, but we'll still need to clean up amyloid and the lysosomal dysfunction.

The problem is the nasty, progressive, synergistic nature of the molecular disorder underlying aging. Unless we intervene comprehensively in the aging process, it's likely that any weak link in the chain will kill you even if you have addressed the others well. We need the SENS full meal deal.

Don:
I think that getting rid of aggregates and crosslinks is important (and also much more realistically attainable in the short term). Both of these catagories deal with the "accumulation of damage" and simply rejuvinating the body with new pristine cells is not going to solve this problem. It would be like trying to clean a soiled toilet by filling it with more water. You need to flush first!

Yes.

manowater989: Hmm....I actually have another related question. What EXACTLY were all of de Grey's Seven Deadly Sins, and what was the proposed fix for each?

See Aubrey de Grey's page on the Seven Deadly Sins of Aging and the embedded links. For more details, see Aubrey de Grey's scientific publications.

manowater989:How much of those fixes rely on theoretical technology that doesn't exist yet, and how much of that is deeply in the works?

There are prototypes in clinical trials for AGE crosslink breakers (ALT-711/ Alagebrium), stem cell therapies, and cleanup of extracellular aggregates (the first such therapy -- active immunization for amyloid beta -- was found too risky in humans; work on a new passive immunization proceeds in mice (2)); the rest are in various stages of preclinical development, from in vitro work on allotopic expression to animal studies of relatively primitive lysosomal enhancement (3,4).

manowater989: Is he claiming that ALL we have to do to escape death is to keep up with maintenance of those 7 things?

No. Leaving aside the niggling point that SENS will address aging and age-related death, but will not cure mortality per se (we could still die by being hit by SUVs or truly horrific infectioins like Ebola, eg), the SENS platform is expected to forestall significantly the molecular causes of aging and age-related death as we currently experience them in a "normal" lifetime. Once we begin to live long enough, newer, more subtle, previously-undetected nasties will start to show up and will need to be addressed.

The idea, however, is that the first-generation SENS interventions will give us enough medically-induced youth to allow us to catch the next wave of life extension technologies, "bootstrapping" our way to a genuinely ageless future through reaching actualrial escape velocity (4).

Osiris is right, though:

You should read through the SENS site and de Grey's publications before asking us to restate it all for him. Afterwards I'll be happy to help you with specific questions.


-Michael

1. Olshansky SJ, Carnes BA, Cassel C
In search of Methuselah: estimating the upper limits to human longevity.
Science 1990 Nov 2;250(4981):634-40
PMID: 2237414

2. Lichtor T, Chauhan NB, Siegel GJ.
Intraventricular Passive Immunization against beta-Amyloid as a Treatment for Alzheimer’s Disease in Transgenic Mice
Presentation, 73rd Annual Meeting of the American Association of Neurological Surgeons in New Orleans.

3. Butler D, Brown QB, Chin DJ, Batey L, Karim S, Mutneja MS, Karanian DA, and Bahr BA.
Degradative pathways responding to age-related protein accumulation involve autophagy and lysosomal enzyme activation.
Rejuv Res 2005, submitted.

3. Du H, Schiavi S, Wan N, Levine M, Witte DP, Grabowski GA.
Reduction of atherosclerotic plaques by lysosomal acid lipase supplementation.
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):147-54. Epub 2003 Nov 13.
PMID: 14615393 [PubMed - indexed for MEDLINE]

4. de Grey AD
[url=http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pbio.0020187[Escape velocity: why the prospect of extreme human life extension matters now[/url]. PLoS Biol. 2004 Jun;2(6):723-6.

#26 reason

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Posted 24 June 2005 - 06:45 AM

See this Fight Aging! post for Aubrey de Grey's brief comment on what is going on in terms of research that overlaps with SENS goals:

http://www.fightagin...15.php#comments

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#27 manowater989

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Posted 25 June 2005 - 04:34 AM

For yet another example of my concerns about this, let me pose a more direct question, and this one I would really appreciate anyone answering if they do know. Really. Are there any laboratories or research centers that are already capable of producing cloned organs, for example? Could you tell me which one(s), maybe post their site links? What about any that may be very close, or at least close to this step?

#28 John Schloendorn

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Posted 25 June 2005 - 05:54 AM

Not sure what you mean by a "cloned organ". But for most definitions that come to my mind, the answer is definitely no. Specifically, there is no single human approved therapy, and not even a clinical trial that involves the transplantation of human embryonic stem cell-derived constructs.
(Rumors to the contrary from Asia have been around for a while, but remained unconfirmable)

Really, the best way to learn where we stand is to go to pubmed and get a few reviews on tissue engineering. You would enter something like "tissue engineering"[TITLE] AND review and for starters prefer a high-profile interdisciplinary publication like science or nature. If you're not familiar with reading scientific literature, you might have to read a few before it starts to make sense, and you may need to spend considerable time searching. But if you are serious about personal longevity, then practising these skills is absolutely essential. If you come up with more specific questions in the process, or need access to full text articles, or just feel like a bit of a rant, that's what imminst is for.

#29 John Schloendorn

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Posted 25 June 2005 - 06:13 AM

We are close to using human embryonic stem cells for therapy, yes. A handful of biotech companies have embryonic stem cell programs, and would from an economic point of view probably like to see them enter clinical trials within no more than a few years. Notably check out Geron and Advanced Cell Tech.

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#30 John Schloendorn

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Posted 25 June 2005 - 06:17 AM

In mice, therapeutic cloning is way more advanced. Here's a couple of references you may want to check out on pubmed:

Rideout WM 3rd, Hocheldinger K, Kyba M et al. Correction of a genetic defect by nuclear transplantation and combined gene and cell therapy. Cell 2002; 109(1): 17-27.

Barberi T, Klivenyi P, Calingasan NY et al. Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and applications in parkinsonian mice. Nat Biotechnol 2003; 21(10): 1200-1207.

Sipione S, Eshpeter A, Lyon JG et al. Insulin expressing cells from differentiated embryonic stem cells are not beta cells. Diabetologica 2003; 47(3): 499-508.

And for embryonic stem cells without cloning:

Chiba S, Ikeda R, Kurokawa MS et al. Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage. Journal of Neurological Science 2004; 219(1-2): 107-117.

Fair JH, Cairns BA, Lapaglia MA et al. Correction of factor IX deficiency in mice by embryonic stem cells differentiated in vitro. Proc Natl Acad Sci USA 2005; 102(8): 2958-2963.

Kofidis T, de Bruin JL, Yamane T et al. Insulin-like growth factor promotes engraftment, differentiation and functional improvement after transfer of embryonic stem cells for myocardial regeneration. Stem Cells 2004; 22(7): 1239-1245.

Burt RK, Verda L, Kim DA et al. Embryonic stem cells as an alternate marrow donor source: engraftment without graft-versus-host disease. J Exp Med 2004; 199(7): 895-904.

Kim D, Gu Y, Ishii M et al. In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell.

Li H, Roblin G, Liu H et al. Generation of hair cells by stepwise differentiation of embryonic stem cells. Proc Natl Acad Sci USA 2003; 100(23): 13459-13500.




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