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#31 boundlesslife

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Posted 18 February 2006 - 09:50 AM

Per maestro949:

So, say we forgot about all this mathematical modeling, and just make the "Singuputer", which will in turn access all of the databases of existing knowledge about genomics, proteomics, etc.  It does the work, and we reap the benefits.  That is what I was attempting to convey.

Tell me how you make this Singuputer without math? Knowledge without application is useless.

Good comment! Computers "compute", and that means math.

The rest of what I'd posted here before wasn't helpful, and I've edited it out. My apologies for taking an unkind shot at someone who's still (as we all are) learning his way around, and reaching for visions at a higher level.

boundlesslife

Edited by boundlesslife, 20 February 2006 - 11:51 PM.


#32 maestro949

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Posted 18 February 2006 - 04:11 PM

I heard (bear in mind that this may not be true) that it is illegal to link up more than a certain number of X-Boxes b/c a supercomputer would result.


This is nonsense. I'd suggest you reconsider where you obtain information like this and treat the source with suspicion.

Maybe I will do some research (or someone more CPU-knowledgeable) will research into how SETI originated, and suggest how this can be applied to the aging disease.


SETI originated by some clever people that realized that searching large data sets for signs of life would take an enormous amount of computing power and applied the concept of distributed computing. By breaking up the data sets into manageable chunks of work and doling the data and algorithms to people who volunteer their personal computers, a very large CPU intensive and time consuming problem is tackeled by lots of individual computers.

You could argue that applying distributed computing to aging is already being done. There are some DC efforts under way to tackle issues surrounding protein folding and anything that helps us understand the basic building blocks of the core components of life also enables us to build theoretical models that we can use to predict and test solutions that will solve the diseases of aging. I suspsect we will see more DC projects like this over time that directly impact aging research.

One of the major issues with attempting computational efforts to "solve" problems is that many of them are what is referred to as NP-complete which means they are so complex that even if algorithms can be designed to tackle them, they would take an exceedingly long time to solve, regardless how many super computers and DC projects you threw at them. Work in theoretical computing (quantum, speed of light computing, biological, etc) and complexity theory needs to make some breakthroughs before we can fully tackle these types of problems with computers alone. Predicting when we make these breakthroughs isn't possible but many feel we are trending in the right direction. Bottom line is that it still takes a great deal of real / non-artificial brainpower and hard hard work to really make progress. So put down that x-box and get to work ;)

Edited by maestro949, 18 February 2006 - 05:05 PM.


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#33 Hypermere

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Posted 18 February 2006 - 06:11 PM

When I asked him, "How do you expect to do this?" he replied, "I just came up with this great idea. Figuring out how to do it is your job!" I didn't think anything would come along that would out do this for outlandishness, but the "So, say we forgot about all this mathematical modeling," proposition leaves it in the dust! Literally!


I tentatively agree. Like I said, I am not a computer wizard in any sense; I can use one, that's about it...it's not my speciality, although I always enjoy learning more when I have time to.
The LAST thing that I want to do is leave any solution in the dust. Thank you for your input. If you have any ideas of how this mathematical modeling is done/who/where/when it will be done, pls do comment!

#34 Hypermere

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Posted 18 February 2006 - 06:17 PM

This is nonsense. I'd suggest you reconsider where you obtain information like this and treat the source with suspicion.
So put down that x-box and get to work ;)


Yes, the XBox comment was one of those hearsay things that I was testing to see if it was true or even relevant. Apparently it is b.s., and thank you for correcting me.
BTW, I don't even have an XBox [lol] I'm too busy trying to make up for years of wasted time and do what I can to maximize my contributions to the WOA (War On Aging).

This is a great thread, not to blow my (or anyone's) horn, let's keep progressing the discussion until we come up with an actual plan.

#35 maestro949

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Posted 18 February 2006 - 06:30 PM

The LAST thing that I want to do is leave any solution in the dust. Thank you for your input. If you have any ideas of how this mathematical modeling is done/who/where/when it will be done, pls do comment!


It's done by crazy people who are smart enough to trick the rest of us that they really don't belong in a padded cell. They usually roam the halls of universities and can be seen mumbling to themselves at night. They usually shun sunlight. [lol] It will never be "done" IMO. Google "theoretical mathematics" and you'll find lots of links. Throw in "microbiology" and you'll see links to the interdisciplinary concepts I rant about in other threads.

This is a great thread, not to blow my (or anyone's) horn, let's keep progressing the discussion until we come up with an actual plan.


My original plan was to let someone solve this problem but they haven't yet so I'm going to tackle it myself. ;)

Seriously though, if I can make even a small dent in the effort that causes even one advancement to happen a few seconds sooner, it might be the one advancement that comes in a few seconds before I expire. Adding as many seconds to my life by taking better care of myself is part two of plan B.

If many people take this approach then those seconds will turn into minutes, hours, days, years and perhaps even decades.

Edited by maestro949, 18 February 2006 - 07:09 PM.


#36 JonesGuy

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Posted 18 February 2006 - 08:48 PM

Another real breakthrough that would help is the ability to augment our intelligence. I have doubts that we're smart enough to augment our intelligence, but some people are really hopeful.

And if that happens, we can create a feedback loop that allows more and more discoveries. I always waffle regarding what field needs the most focus, because which discoveries are likely to come first make a big difference.

#37 maestro949

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Posted 18 February 2006 - 09:57 PM

Another real breakthrough that would help is the ability to augment our intelligence.  I have doubts that we're smart enough to augment our intelligence, but some people are really hopeful.


I'm hopeful but I don't think it's anything near-term and I don't count on it. Personally I think we are already intelligent enough to solve all of the diseases of aging but we lack much of the data, tools, resources and don't have enough people working on the problems. I don't necessarily see that changing. If I'm correct, then the only thing we can do is try to improve efficiency and effectiveness, i.e. working smarter and harder.

And if that happens, we can create a feedback loop that allows more and more discoveries.  I always waffle regarding what field needs the most focus, because which discoveries are likely to come first make a big difference.


It's impossible to accurately predict where the breakthroughs will come and when. If we could predict them accurately then we would already have the data to achieve them and know exactly where to place our efforts. The only thing we can guarantee is that if we don't push forward in as many fields as we can that that seem promising then, well, we all die. If we all ganged up on one problem that we thought was a silver bullet and it turned out we were wrong? Yup. Dead too. [glasses] I love pointing out the obvious.

#38 th3hegem0n

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Posted 18 February 2006 - 10:37 PM

What if we all pitched in to one problem and it turned out to be RIGHT?

Well then there ya go... the answer is simple- Don't be wrong!

Duh...

#39 Hypermere

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Posted 26 February 2006 - 03:31 AM

You have no idea what we're doing already! The lysoSENS project currently involves collaborations between at least three world-leading and several smaller labs from different universities and these aren't just sunday afternoons' collaborations, but we actually discuss, coordinate, visit and send each other stuff all the time. Targeted Methuselah Foundation funds are in this way allocated at high leverage, interdisiplinary projects carefully desined to give us the most bang for our buck. If anything, then the situation is set to grow and improve


Wonderful. I want in. With all due respect, do not doubt my dedication, I will work 24 hours a day if given a real opportunity. And (to reply to you and others in this thread) I have no family to care for.... just humankind.

#40 John Schloendorn

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Posted 26 February 2006 - 05:35 PM

I want in.

Very well. If you intend to stay in the mitochondrial field, I would recommend you coordinate and collaborate with the allotopic mitochondrial gene expression project that MF and imminst affiliates are about to create elsewhere. For a start, contact Osiris and discuss what your and his future labs are dreaming of doing and how it might be productively related.

#41 JonesGuy

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Posted 26 February 2006 - 08:22 PM

I will agree that expertise in mitochondria will be key to curing aging.

#42 Mark Hamalainen

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Posted 27 February 2006 - 01:15 AM

OF COURSE THE CURE TO AGING ALREADY EXISTS, AND WE ARE BEING KEPT IN THE SHADOWS


Is this some kind of conspiracy theory?? Don't forget about Occam's Razor...

Could you take the time to outline what you understand about the role of mitochondria in aging? How familiar are you with the ideas of allotopic expression and protofection?

#43 Hypermere

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Posted 27 February 2006 - 12:14 PM

Sure, Osiris...later tonight or tomorrow...I have to leave for work now.  In short, I do remember reading about two purported reasons that the final 13 mt proteins are not incorporated in the nucleus (hydrophobicity and code conversion issues)

Of course, even if that problem were overcome, who's to say if it would make any difference.  To change the subject, Dr. Kenyon's work, not related to mitos, shows tons of promise.  In fact, 13 years ago they were able to double the lifespan of C. elegans.

[/quote]OF COURSE THE CURE TO AGING ALREADY EXISTS, AND WE ARE BEING KEPT IN THE SHADOWS[quote]

Maybe true, maybe not. I threw that one out just to keep everyone on our toes, because you never know. There is alot of money in death and sickness.

#44 Mark Hamalainen

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Posted 27 February 2006 - 03:26 PM

Of course, even if that problem were overcome, who's to say if it would make any difference.  To change the subject, Dr. Kenyon's work, not related to mitos, shows tons of promise.  In fact, 13 years ago they were able to double the lifespan of C. elegans.


If I remember correctly, that life extension was a diapause phenomenon. Small organisms like that can go into a hibernation like state to slow down their metabolism, which is useful to survive periods of low temperature or scarce food. Unfortunately, for evolutionary reasons this ability has not been maintained in large mammals. The closest we can get is calorie restriction (or a drug that mimics that effect), and we know how weak a strategy that is for extending life...

Don't take my word for it, see the attached paper.

Attached Files



#45 Mark Hamalainen

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Posted 27 February 2006 - 03:30 PM

There is alot of money in death and sickness.


Like most conspiracy theories, this one fails because if that cure existed, a significant number of people would have to know about it and the chances of keeping it secret decrease exponentially with each additional person that knows. Besides, there is much more money to be made in treating aging than there is in maintaining the status quo.

#46 JonesGuy

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Posted 27 February 2006 - 03:51 PM

In addition, the people with the cure would have to be the people who profit from death and sickness.

The could patent the process, to protect research into it, but that would make the process public.

#47 mitohunter

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Posted 04 March 2006 - 04:00 AM

This was 'hypermere' but for some reason my login stopped working recently.
So hi, here I am, with post #1.
anyway, had a dumb question...
1. I understand that mitos were originally bacterial that, imo, infected us possibly.
2. We use them for ATP production.
3. Question: has any researcher ever considered designing a simple organisim that has no mitos at all? Maybe the gDNA would have to find a way to make energy via other pathways.
4. The idea is that (imo) mitos both allow us energy and also cause senescence.

Feel free to laugh and comment. I just shoot out ideas sometimes and hope for the best. My guess is that the thing would never live a second, but I don't know.

#48 Aegist

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Posted 04 March 2006 - 05:12 AM

FOr a start, the mitochondrial predecessor prokaryote (assuming the theory is true) didnt infect 'us' in any respect. That symbiotic relationship was clearly formed long before ..well, i'm not sure when, but I am willing to guess it happened before multicellular organisms existed. It is possibly the key factor which started the differentiation from the prokaryote down towards modern day eukaryote? Even if it isn't, mitochondria, afaik, are present in every form of eukaryote cell, even photosynthetic cells...

Start potentially educational section
OK, back to basic biology here: prokaryotes can be grouped into 4 categories of how they obtain energy:
Photoautotroph: use light to drive CO2 into organic compounds. Includes cyanobacteria, and all photsynthetic eukaryotes fall into this nutritional category.
Chemoautotroph: Use CO2 as carbon source and use inorganic substances as energy source. Energy is obtained by oxidizing NH3, FE2+ etc depending on the species.
Photoheterotrophs: Use light to generate ATP, but must obtain their carbon in an organic form.
Chemoheterotrophs: Must consume organic molecules for both energy and carbon

I just put that there so we have some basics to work with, that is where we can get enrgy from theoretically. Actual energy production comes in 3 major forms though: Metabolism, Photsynthesis, and respiration. Our metabolic pathway is Glycolysis, which produces ATP from the breakdown of organic molecules. It does not require oxygen to do this, but there needs to be a way to dispose of the end products. This is done by either fermentation or respiration. Fermentation, i think, makes a little more energy, but still results in organic waste products which need ot be flushed basically (like ethanol and lactic acid). Respiration on the other hand produces CR#P LOADS of energy, and results in water. It is quite possibly the only reason gargantuan behemoths such as ourselves could have possibly evolved: the fact that we can produce enough energy to maintain ourselves from the same amount of fuel.

The theory behind respiration basically revolves around cyanobacteria, the prokaryotes which use CO2, water and sunlight to make O2. When they came to be, they flooded the earth with all of this incredibly harmful molecule, which caused a major selective pressure to adapt or die. Many prokaryotes would have been driven into extinction, some managed to survive in anaerobic conditions, while some were fortunate enough to evolve in such a way where they utilized the oxidizing power of O2 to pull electrons from organic molecules down existing transport chains. "Thus, aerobic respiration may have originated as modifications of electron transport chains co-opted from photosynthesis" (I'm taking this from Biology, by campbel, reece, and mitchel)

From there, the theory goes ancestral prokaryotes formed an endomembrane system (endoplamic reticulum nucleus etc), then it formed a symbiotic relationship with an aerobic heterotroph prokaryote which evolved into the mitochondrion, which is what we have today, while some of them also bonded with a photosynthetic prokaryote, which gave rise to the plant lineage...
End potentially educational section

SO, in response to your Question mitohunter/hypermere, obviously organisms exist without mitochondria, but no eukaryotes or higher do. In order to try to remove the mitochondria from a eukaryote, would be a...gargantuan task. But if you did, I doubt the energy produced by glycolysis/fermentation AND photosynthesis would even be enough to maintain a complicated life form. But I have nothing to back that up with. Maybe a combination of organic, inorganic, and phototrophic energy sources would meet the enrgy demands.

But its all very very sci fi and way beyond anything any could possibly do with biology atm. We have trouble changing 1 gene, let alone restructing an entire eukaryotic cellular structure and the supporting genetic code.

#49 John Schloendorn

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Posted 04 March 2006 - 05:36 AM

organisms exist without mitochondria, but no eukaryotes or higher do

One can make viable yeast or cultured mammalian cells without mitochondrial genomes, which leaves the mitos basically inactive (google rho0). Not sure where that would take Hypermere's argument though...

#50 Aegist

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Posted 04 March 2006 - 05:42 AM

Oh yeah, petites right? Yeast can respire and ferment though, so they can already live aerobically and anerobically. Mammals I guess do have limited anaerobic capacity (producing lactic acid) but clearly we couldnt survive on that energy source

#51 JonesGuy

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Posted 04 March 2006 - 05:15 PM

Question: has any researcher ever considered designing a simple organisim that has no mitos at all?


I believe this is an essential element of SENS. I do not know of any research group working on this, but I have not looked.

#52 mitohunter

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Posted 04 March 2006 - 10:59 PM

[quote]But its all very very sci fi and way beyond anything any could possibly do with biology atm. We have trouble changing 1 gene, let alone restructing an entire eukaryotic cellular structure and the supporting genetic code./QUOTE]
I doubt it. We change genes everyday. i want to see what happens with a worm or mouse with no mitos.

#53 JonesGuy

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Posted 04 March 2006 - 11:05 PM

I think everyone here does too.

Do you know anyone who could get funding for this type of research?

#54 mitohunter

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Posted 04 March 2006 - 11:10 PM

My perspective
At some point in evolution, prokaryotic cells were infected by mitorchondria imo. Look at this work to understand:

The genome sequence of Rickettsia prowazekii and the origin of mitochondrial; Anderson et. al., Nature, 396, 12, November 1998.

In other words, I think that our existence is a catch-22. We are alive b/c of mitos, and they have a major role in killing us as individuals (Kenyon, et. al.).

To cure aging, I see it as "let's cure ourselves of this bacterial infection". I'll be starting for my Masters next year, and will have many debates about this, but, again, I'm just kicking around ideas. Whatever it takes, the goal is the same.

#55 mitohunter

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Posted 07 March 2006 - 12:37 AM

There have been no further replies in this thread, because the highly-educated here are comtemplating my previous post. Before we get rid of AIDS, bird flu, or the common cold, we have to get rid of mitos but yet still survive and meet our cellular energy needs.
It is similar to the global oil vs. solar energy issue, if you'd like a metaphor.

On a side note, I do believe in the butterfly effect, and have been doing alot for us, every day, every minute. No matter how many rocks and hard-places you are stuck between, NEVER GIVE UP.

#56 Mark Hamalainen

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Posted 07 March 2006 - 03:35 PM

I believe this is an essential element of SENS. I do not know of any research group working on this, but I have not looked.


One of the goals of SENS is to transfer the mitochondrial DNA into the nucleus. The mitochondria would still remain and be fully active, but all the genes that are necessary from the mtDNA would be expressed in the much safer location of the nucleus. This would prevent the accumulation of mitochondria with damaged DNA, as well as the accumulation of rho- cells, which John has already mentioned (they have no mtDNA at all, are aneorobic, and toxic to their local environment).

Mitochondria are not only associated with ATP production, they play many other important roles in metabolism, there are 1000's of proteins associated with the mitochondria! Even if you could, I don't see what the advantage of eliminating mitochondria would be since you would have to replace them with something else that performed equivilant functions... seems rather circular.

The idea is that (imo) mitos both allow us energy and also cause senescence.


Aging is not a direct result of something that mitochondria do. Aging is a result of the less than 100% efficiency of all processes (2nd law of thermodynamics). This applies to energy production in the mitochondria, to the breakdown of intra/extracellular junk, to the storage of genetic information, and many others... A rational strategy for curing aging takes into account this larger perspective and divides aging into categories that can be treated in specific and well defined ways, and that is exactly what SENS does.

#57 Mark Hamalainen

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Posted 07 March 2006 - 03:42 PM

I think what you are looking for in the mitochondria is some sort of 'magic bullet' that could give us a huge step towards immortality. Unfortunately, we know that is extremely unlikely to exist... that shouldn't be discouraging though. The problem of aging, if not simple, has been well defined. We just need to roll up our sleaves and do the research!

#58 maestro949

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Posted 07 March 2006 - 04:31 PM

Mitos definitely sound like a contributing factor but when I think of all the things that can go wrong I'm convinced that there are no silver bullets. Even hundreds of relatively small advancements will only yield modest gains. SENS does a good job at describing what needs to be done fairly well though I'm sure there are lot of loose ends that need to be tied up and ratholes that each problem will lead us down. The how of SENS still needs a lot of work IMO. In general though taking an engineering approach is absolutely the only way to solve aging. The challenge is determining what level of engineering effort is needed and where the investment needs to be focused. My take is that it will need to be rather hard-core, i.e. reverse engineer the entire set of blueprints, build a model organism in sitro and then build tools that will allow trial and error on a mass scale. Regardless what approaches we take though, whether it be a super-simulators, efforts like LysoSENS, research into nanotech or AI to the rescue it's going to be hard work and likely will require some significant breakthroughs in knowledge, tools and techniques. A combination of all of the aformentioned approaches will probably be required.

Edited by maestro949, 07 March 2006 - 09:58 PM.


#59 mitohunter

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Posted 08 March 2006 - 12:47 AM

Upon reading the previous posts since my last one, my first thought is:
Years ago, Dr. Kenyon engineered a C. elegans with a tripled life span. Today, for us humans, nothing has changed.
What does anyone think about this? If we can now triple the lifespan of ANYTHING, then what is the bottleneck? That is one very good spot to take a look at, imo.

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#60 John Schloendorn

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Posted 08 March 2006 - 02:31 AM

Put in another way, she extended C.elegans lifespan by approximately 40 days...

i want to see what happens with a worm or mouse with no mitos.

A good way to find out is to hold your breath [tung]




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