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Engineering Approach vs Fixing metabolism


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#1 eternaltraveler

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Posted 03 August 2007 - 01:22 AM


OK, that is the second comment on this line. Why is it so funny?


They are starting with actual human research, which is rare enough, and applying it to non-model organisms (i.e. organisms that have no or little relevance to us) which is a step below what the biogerontology establishment is doing, and is basically using humans as a model organism for lobsters. All they do is study metabolism without ever trying to fix anything, and usually in "model" organisms like yeast and worms, and on the very rare occasion actual mice.

What's ironic is that studies like these on metabolism get funded so easily, but to fund actual engineering interventions that have a chance of doing anything in the next 50 years we need to set up our own entirely privately funded foundation. A paradigm shift is in order.

Though I guess if you really are interested in lobster aging I suppose this could be interesting [sfty]

#2 digitalhammer

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Posted 03 August 2007 - 01:42 AM

What's ironic is that studies like these on metabolism get funded so easily, but to fund actual engineering interventions that have a chance of doing anything in the next 50 years we need to set up our own entirely privately funded foundation.
[sfty]


Is the comparative difficulty of getting funding for applied anti-aging human research due to the pretentiousness of the field's opponents? (a.k.a. the types who think death by age-related causes should be a natural part of life)

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#3 Aegist

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Posted 03 August 2007 - 01:46 AM

Though I guess if you really are interested in lobster aging I suppose this could be interesting [sfty]

Well i do think that researching long lived organisms could be very useful to our understanding of ageing. We have so many short lived ones, it might be worth making a very long lived organism (like the turtle? the hydra? the lobster? whichever can be found to be the most non-senescent) into a model organism and studying its (non)ageing thoroughly.

That is why, as I said, this research could be interesting. (but only if lobsters are truly non-senescent.)

#4 eternaltraveler

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Posted 03 August 2007 - 02:01 AM

yes, it paints a better picture of how to tweak metabolism so that damage doesn't accumulate as fast. But metabolism is so ridiculously complicated that it could take centuries use such a strategy to achieve negligible senescence in humans, and even then, the damage that you already have wouldn't go away.

Research into repairing the damage, rather than slowing it's accumulation, is far more logical. If you can repair the damage once, you can do it again and again.

That's why I think the approach you are outlining above is fundamentally flawed. Not because it will never bear fruit, but because there are other avenues that are likely to bear fruit much sooner, that aren't getting nearly enough attention. The kind of approach involving studying little bits of metabolism and tweaking this and that is getting a lot of attention. The NIH funds this stuff all day and night.

The scientists doing this stuff will swear up and down that aging doesn't have a chance in hell of being fixed in any of our lifetimes, because they know just how complicated metabolism is, and fixing metabolism is the only thing that fits in their conception as being a fix for aging. And many of them are already old, and they know that just fixing metabolism so they don't accumulate any more damage is just going to leave them "old" forever.

#5 Liquidus

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Posted 03 August 2007 - 02:09 AM

Well said elrond, I agree with your principles. Repairing the damage is massively more beneficial than slowing down aging. Slowing down aging leaves the assumption that natural death related to aging is still inevitable. However, through repair mechanisms, as long as there's a will to repair, you could technically continue to repair for as long as possible. And as technology becomes more advanced, the gaps between the periods required for repair will become longer and longer. It's a win-win in both cases.

Dr. De Grey definitely paints this picture the best in most of his discussions more so than anyone else I've watched/heard so far. I think it would be beneficial for a 'committee' of say credible sources to make a statement that 'slowing down aging is impractical compared to the alternative of just repairing aging altogether'. I know Dr. De Grey tries to convey this point, but as per this topic, it's evident that slowing down aging is still a priority.

I suppose that it's better to have people working on curing aging in some regard, rather than not having them involved at all. I just think it would be more beneficial if all contributers focused on the same thing at once (and more importantly, the most proficient thing, aka repairing not slowing down).

From a socio-psychological standpoint, people (as elrond mentioned) would be much more accepting of the 'impossibility' of reversing the aging process, rather than just slowing down aging and always being old (for those who are old to begin with).

#6 John Schloendorn

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Posted 03 August 2007 - 02:38 AM

I just find it ironic that immortalists need to place some of their hopes on scientists who so eloquently declare that they want to have nothing to do with any fixing of human suffering. Perhaps posting smilies is not the appropriate response to what I consider appealing tragedy. Least of all when it is not fiction. Apologies...

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#7 Liquidus

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Posted 03 August 2007 - 02:52 AM

I just find it ironic that immortalists need to place some of their hopes on scientists who so eloquently declare that they want to have nothing to do with any fixing of human suffering.  Perhaps posting smilies is not the appropriate response to what I consider appealing tragedy. Least of all when it is not fiction. Apologies...


I would agree with you. Scientists are supposed to be the pioneers of innovation and helping society. Why some choose to ignore this calling based on some personal issue, especially when based on false information, is completely absurd.

Luckily for us though, we have people like you John, and other's like Dr. De Grey and Ray Kurzweil who are the true pioneers in this cause, and deserve all the true credit. Anyone who supports this cause though is worthy of praise in my books (and that doesn't come easily :))

#8 John Schloendorn

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Posted 03 August 2007 - 06:14 PM

I'm not at all trying to say that there is no place for sustainable fishery research in the world. The irony is only that immortalists are placing their hopes on them. Anyway, thanks for the encouragements.

#9 maestro949

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Posted 03 August 2007 - 08:56 PM

That's why I think the approach you are outlining above is fundamentally flawed.  Not because it will never bear fruit, but because there are other avenues that are likely to bear fruit much sooner, that aren't getting nearly enough attention.  The kind of approach involving studying little bits of metabolism and tweaking this and that is getting a lot of attention.  The NIH funds this stuff all day and night.


Is the thinking behind picking apart the metabolism one chunk at a time that we will eventually find a root cause or theory of aging that provides a silver bullet solution? If so, this is clearly flawed as the model of aging is clearly not a tree with roots but rather a tangled ball of yarn.

I've been through much of the standard gerontological literature and read most of the theoretical basis of SENS but I still don't feel confident that either guarantee escape velocity in our lifetime. The whole grant process of throwing a few sheckles at little research efforts will take eons. The SENS raise-a-trillion dollars and test a bunch of complex and hypothetical therapies is fraught with the same risks that have plagued cancer research for the past several decades. It seems like a game of whack-a-mole that might leave us in the same place we are now.

The only thing that feels even remotely close to delivering a guaranteed solution to aging is a brute force attack on the complexity by building a comprehensive systems model of aging from which many additional and refined SENS-like theoretical engineering possibilities will emerge. The thinking behind this is start with a crude model and continually add more and more genomic, proteomic and biomarker data as it becomes available. Continuously refine this model until it's predictive capabilities reach a level where economical engineering efforts have a high chance of success. It'll take awhile to build this model and get it to the point mentioned but if it can be done it guarantees a certain level of success.

#10 Athanasios

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Posted 03 August 2007 - 09:54 PM

The only thing that feels even remotely close to delivering a guaranteed solution to aging is a brute force attack on the complexity by building a comprehensive systems model of aging from which many additional and refined SENS-like theoretical engineering possibilities will emerge.  The thinking behind this is start with a crude model and continually add more and more genomic, proteomic and biomarker data as it becomes available.  Continuously refine this model until it's predictive capabilities reach a level where economical engineering efforts have a high chance of success.  It'll take awhile to build this model and get it to the point mentioned but if it can be done it guarantees a certain level of success.

As well as learning to build powerful tools and techniques to empower us to go beyond traditional approaches in applying engineering principles (I am thinking synthetic and nanobiology here).

At what point does a systems approach fail? At some point we can only model the system, not understand it. This will prevent an engineering approach, no? We would have to play with inputs and outputs of a very complex model.

#11 maestro949

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Posted 03 August 2007 - 11:53 PM

As well as learning to build powerful tools and techniques to empower us to go beyond traditional approaches in applying engineering principles (I am thinking synthetic and nanobiology here).


Absolutely. Building all of the tools that biologists and biochemists need to model and simulate all of this complexity is the first requirement. Starting small and evolving these as computing performance improves will be necessary too.

At what point does a systems approach fail? At some point we can only model the system, not understand it.  This will prevent an engineering approach, no? We would have to play with inputs and outputs of a very complex model.


This is the challenge with modeling. We'll be able to assemble lots of small models and piece them together ourselves but we'll be quickly overwhelmed once we interconnect more than a few of them. It'll take machine learning and some heavy duty statistical analysis to go beyond a certain level of complexity but I believe it's doable. We need to assemble a hardcore team of theoretical mathematicians, statisticians, comp science PhDs, biologists, chemists, lock them in a room and not let them come out until they have a set of specifications for the tools they need and a roadmap for building such a model. :)

#12 Athanasios

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Posted 04 August 2007 - 12:07 AM

It'll take machine learning and some heavy duty statistical analysis to go beyond a certain level of complexity but I believe it's doable.

Definitely.

#13 eternaltraveler

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Posted 06 August 2007 - 06:03 AM

Is the thinking behind picking apart the metabolism one chunk at a time that we will eventually find a root cause or theory of aging that provides a silver bullet solution?


A lot of this is certainly a problem, however…

The only thing that feels even remotely close to delivering a guaranteed solution to aging is a brute force attack on the complexity by building a comprehensive systems model of aging from which many additional and refined SENS-like theoretical engineering possibilities will emerge


This is also a problem :))

That’s just it. I hate to say it, but we don’t need to know how damage occurs. We don’t. We need to know two things. We need to know what damage occurs. And we need to know how to repair it once it occurs. We already know what damage occurs. That leaves us with step 2. Fixing it.

At what point does a systems approach fail? At some point we can only model the system, not understand it. This will prevent an engineering approach, no?


We don't need to understand every biochemical interaction to fix the damage that occurs as a side product, just as a bridge engineer doesn't need to understand the quantum mechanical binding interactions the corrosion process of the steel his bridge is made of.

What does a bridge engineer do when some of the support beams become corroded? He replaces them (hopefully). He can go on fixing the bridge like this forever without ever having any idea precisely what mechanisms cause the corrosion of the metal. He just needs to know the metal does indeed corrode over time and needs repairing. Knowing more details of the corrosion/erosion process enables the bridge engineer to design other systems to make the bridge last longer between repairs. It does not stop damage from occurring. Even if you figure out that slapping a coat of paint on the metal slows it from rusting further it doesn’t do a damn thing to the metal already corroded away.

As I said, we know what types of damage aging does to us, and very few people are actively trying to fix any of them. You don’t need to be a fan of Aubrey’s favorite ideas for fixes so long as your agenda is focused toward doing the fixing. First we need to figure out how to fix ourselves once (repair the damage), then it becomes more logical toward putting our efforts into learning how to go longer between tune ups by optimizing every biochemical pathway and understanding every interaction.

We have been using engineering approaches to dealing with disease states for centuries. What happens when someone’s heart is failing? We replace it. And yet we still don’t know everything that leads to this heart damage that required the replacement in the first place. The medical establishment is only now barely starting the realize that cardiac tissue doesn’t even die quickly from ischemia, but just decides to kill itself as a result(apoptosis), and yet this didn’t stop people from getting heart transplants 40 years ago. We do the same with many other major organ systems. Organ replacement is absolutely an engineering approach. This is what I mean by thinking like an engineer. This is what we few immoralists have to do if we are to make a difference.

#14 eternaltraveler

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Posted 06 August 2007 - 06:06 AM

I will say that the only organ system we will eventually need to understand in much more detail is the brain, but we can probably all last until 130 if we can deal with the types of damage that are presently known, that gives even the oldest of us here quite a long time for the endless push of regular science to churn out some answers for us. All I am saying is that we immortalists are few, and we need to be the butterflys that flap our wings in exactly the right way to create the future we desire.

#15 Luna

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Posted 06 August 2007 - 07:05 AM

Umm, Elrond, thought they already know how to make new neurons and the like?

#16 maestro949

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Posted 06 August 2007 - 05:58 PM

we don’t need to know how damage occurs.


Not always but damage itself can be very complex. It has many sources, is multivariate and can iteratively lead to more damage. The immune system is an example. Heterogeneous gene expression changes with age could also be viewed as damage. Also, what if the damage is continuous where it returns immediately after you mop it up, for example, an errant process or pathway that has gone haywire? If this is the case then you need to understand how it is occurring and your engineering effort has to target the very metabolic reactions you'd like to remain ignorant about. If the damage is from sudden events such as stroke, heart failure, non-aging disease, an aggressive environmental injury from toxin, virus or bacteria the damage can be even more troublesome. Surely these can be dismisses as problems to be dealt with by standard medical care and pathologists but they still need to be repaired as the system is now compromised and declining even faster. Systems biology will deliver predictive tools and knowledge for both preventing and fixing these as well as the slower accumulating aging damage. As an immortalist these are just as valuable to me :)

We need to know two things. We need to know what damage occurs.  And we need to know how to repair it once it occurs. We already know what damage occurs. That leaves us with step 2. Fixing it.


Whereas the systems approach delivers the ability to predict or detect the changes very early and engineer personalized solutions at any stage of the process, particularly where it is most economically suitable and perhaps even feasible. #2 "fixing it" becomes a more likely event when numerous possible solutions with various cost/benefits are available to us.

What does a bridge engineer do when some of the support beams become corroded? He replaces them (hopefully). He can go on fixing the bridge like this forever...


But if that same bridge had built-in mechanisms for repairing and replacing its own faulty components (designed by some ancient race of Atlantians), time permitting, a good engineer would study these mechanisms, reverse engineer them and then make repairs to these rather than simply trying to patch up the bridge with his own creative fixes to the structure itself. Surely you could argue that through serendipity he might hold the bridge up a bit longer but if the goal is to never let the bridge fall, leveraging the existing designs will likely trump the simplistic hack attempts.

To live as long as it does the body has numerous mechanisms for preventing and mopping up damage. I think it would be prudent to see if we can find and shore those up if we can rather than only going after every damaged endpoint and attempt to engineer a fix for each. Their are just too many things that can be damaged. Too many cell types, protein complexes, DNA, pathways, expression levels, organ systems, etc. The clock will run out on most of us if we are going after the low level fix for each as it only takes one weak link in the chain for the system to collapse. Perhaps it will run out with the systems approach too but it feels like more of a sure bet to me.

IMO it's the tortoise and the hare. Systems biology is the tortoise but will be what delivers sustainable longevity in the end. The good news is that it doesn't have to be either or as progress is either niche adds value to the other.

Edit: Fixed typo

Edited by maestro949, 07 August 2007 - 06:11 PM.


#17 eternaltraveler

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Posted 07 August 2007 - 07:10 AM

Not always but damage itself can be very complex. It has many sources, is multivariate and can iteratively lead to more damage. The immune system is an example.


And yet, today, we can replace essentially a person’s entire immune system with a bone marrow transplant.

If the damage is from sudden events such as stroke, heart failure, non-aging disease, an aggressive environmental injury from toxin, virus or bacteria the damage can be even more troublesome.


Organ transplant, stem cell therapy. Aging damage is far more troublesome as it is far less specific than the examples you give.

Systems biology will deliver predictive tools and knowledge for both preventing and fixing these as well as the slower accumulating aging damage.


Whereas the systems approach delivers the ability to predict or detect the changes very early and engineer personalized solutions at any stage of the process, particularly where it is most economically suitable and perhaps even feasible. #2 "fixing it" becomes a more likely event when numerous possible solutions with various cost/benefits are available to us.


Don’t misunderstand me. I am not dismissing the value of systems biology. Far from it. I think it is very valuable. I just happen to think there are other things that are presently more valuable. In the future that will change. And if you think it is your strongest suit, then by all means pursue it. There are certainly engineering problems that we don’t remotely have clear cut solutions for. By all means please find these solutions for us =)

Also, what if the damage is continuous where it returns immediately after you mop it up, for example, an errant process or pathway that has gone haywire? If this is the case then you need to understand how it is occurring and your engineering effort has to target the very metabolic reactions you'd like to remain ignorant about


Please give an example of this that would not be fixed by repairing damage in general. If the damaged pathways is within a certain percentage of a population of cells, those cells should be destroyed, and replaced. Fixing all these cells individually strikes me as harder. If you can prove me wrong, you’d make me a happy man. If you’re speaking about the endocrine system I’m of the opinion that if you can repair the damage in it’s constituent parts it would probably work out.

But if that same bridge had built-in mechanisms for repairing and replacing its own faulty components (designed by some ancient race of Atlantians), time permitting, a good engineer would study these mechanisms, reverse engineer them and then make repairs to these rather than simply trying to patch up the bridge with his own creative fixes to the structure itself. Surely you could argue that through serendipity he might hold the bridge up a bit longer but if the goal is to never let the bridge fall, levering the existing designs will likely trump the simplistic hack attempts.

To live as long as it does the body has numerous mechanisms for preventing and mopping up damage.


You’re right. The body does indeed have mechanisms for dealing with certain types of mostly quickly accumulating damage (not so much the intrinsically slowly accumulating damage as there has never been much selective pressure to deal with that), and these systems fail just as the systems they are designed to repair fail. And replacing/repairing these systems certainly would be a good thing. And this absolutely falls under the category of “repairing the damage”. However, I think you’re looking too deeply into where to make the repairs. As I said, if the immune system goes completely out of wack, it can be replaced (there is certainly the problem of graft vs host disease, but with engineered stem cells made from our own cells this shouldn’t be a problem). Currently the biggest difficulty is safely killing off malfunctioning immune system that is already there. Full body irradiation does the trick, but vastly increases other risks.

There is nothing intrinsically irreplaceable involved in many other regulating mechanisms in the body. Kidney’s, and liver should be obvious (and if you’ve ever taken biochemistry you are well aware that most of it takes place in the liver :))). Other organ systems that rely more heavily on innervation to function have been troublesome in the past, but mainstream medicine has made a lot of headway with re attaching peripheral nerves.

If you’re talking about intracellular repair mechanisms failing, that’s true. But that’s taken care of by replacing the cells or entire organs.

But if that same bridge had built-in mechanisms for repairing and replacing its own faulty components (designed by some ancient race of Atlantians), time permitting, a good engineer would study these mechanisms, reverse engineer them and then make repairs to these rather than simply trying to patch up the bridge with his own creative fixes to the structure itself. Surely you could argue that through serendipity he might hold the bridge up a bit longer but if the goal is to never let the bridge fall, levering the existing designs will likely trump the simplistic hack attempts.


Time is not permitting. However, our simplistic hack attempts might just buy us the time we need. The march of science will churn out the more complicated solutions in time, but not less than any of us have.

To live as long as it does the body has numerous mechanisms for preventing and mopping up damage. I think it would be prudent to see if we can find and shore those up if we can rather than only going after every damaged endpoint and attempt to engineer a fix for each. Their are just too many things that can be damaged.


Every damaged endpoint? The great news is that there are remarkably few fundamental types of damage. Whatever tissue they occur in there is a great homogeneity. There are countless routes to that damage.

IMO it's the tortoise and the hare. Systems biology is the tortoise but will be what delivers sustainable longevity in the end. The good news is that it doesn't have to be either or as progress is either niche adds value to the other.


I can’t disagree at all with what you are saying in this last paragraph. However, for any of us here, now, the hare is our only chance (aside from cryonics I suppose :))). Also as you say, either niche does indeed add value to the other. And we hares will be more than happy to make the hand off to the tortoise as it goes on endlessly lumbering past us. However the real point is there is about a million tortoises to every hare. And we desperately need more hares to get us through to the next phase.

#18 eternaltraveler

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Posted 07 August 2007 - 07:20 AM

Umm, Elrond, thought they already know how to make new neurons and the like?


To a somewhat limited extent that is certainly true, however that doesn't mean the information encoded in the old neurons would be carried over. In the post you are refering too I was mostly concerned with preservation of identity, rather than preservation of the brain's function as an organ.

In anycase it's reasonable to assume that if other types of damage in the brain can be repaired (before they lead to even greater damage themselves), identity would remain reasonably intact till at least the age of 120, which is basically the farthest data point we have.

I'm not too worried about diseases like alzheimer's beyond the 20 year mark, as there are already methods that show great promise in curing/preventing alzheimer's (vaccine approach seems great, abeta is removed, and hyperphosphoralated tau accumlation is seemingly halted, if not removed)

#19 Luna

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Posted 07 August 2007 - 08:10 AM

Best idea is probably to develop the engineering approch and start researching the metabolism at low scales so one day we could just throw away the rejuvenation therapies and becomes "naturnally" immortals.

When can I get wings btw?


Oh and BTW Elrond..

A question that always troubled me.
At one point, with brain regeneration, all the old neurons will die and we'll have 100% new ones.
Will it affect us anyhow? as the brain don't really have a "core" I guess not.. but it's still interesting, will we die and have a seperate counciusness within us that thinks it's us?..
It's actually kinda hard.. what really defines us?
Why dosen't the body work automatically..?

I know it probably sounds strange but it actually bothered me @@..

Edited by winterbreeze, 07 August 2007 - 08:27 AM.


#20 maestro949

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Posted 07 August 2007 - 12:47 PM

Organ transplant, stem cell therapy. Aging damage is far more troublesome as it is far less specific than the examples you give.


Doesn't this suggest that it might be more economical to see if we can find ways to deal with these problems upstream by monitoring the transcriptome, protein levels and metabolites and then adjust the transcription factors and signaling parameters there? It's true that this approach has been a dismal failure for the past X years but isn't that due more to fact that we're working with an incomplete picture and lack of tools to understand metabolism and the -omics that drive it? The tools are emerging now that will allow us to do this via RNAi and high throughput analysis. Wouldn't it be prudent to explore this space?

I can’t disagree at all with what you are saying in this last paragraph. However, for any of us here, now, the hare is our only chance (aside from cryonics I suppose wink1.gif). Also as you say, either niche does indeed add value to the other. And we hares will be more than happy to make the hand off to the tortoise as it goes on endlessly lumbering past us. However the real point is there is about a million tortoises to every hare. And we desperately need more hares to get us through to the next phase.


It's true that there are plenty of efforts looking at the -omics space and metabolism but I don't even see the systems biology tortoise on the racetrack. There isn't anyone working on true systems biology in any significant manner and those that are working on it are significantly underfunded. I see lots of scattered prototypes and resulting research papers that hint at how great it would be to take it to the next level but no full scale efforts to transform biology into the informational and tools driven science that it needs to evolve into for aging research to benefit.

In my opinion it's not a division between two camps of engineers vs. those that seek to fix metabolism because fixing broken genes and transcription that leads to broken metabolism is just as much engineering as is repairing damaged endpoints and swapping in replacement parts. If there's division in the gerontology field over this then it's really just a debate over hypothetical solutions to the same problems which really should simply boil down to a cost/benefit analysis. Engineering will be the ultimate solution regardless where it's applied. Better organized information about the biological system and working models will help answer those questions.

Good engineering starts with a complete parts list and a specific functional description of the system. We have neither but the tools are evolving to flush both of these out. This needs to be accelerated at a much greater rate.

#21 caston

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Posted 07 August 2007 - 02:09 PM

And yet, today, we can replace essentially a person’s entire immune system with a bone marrow transplant.



Organ transplant, stem cell therapy.  Aging damage is far more troublesome as it is far less specific than the examples you give.


Deep down inside I will tell you the real reason why I prefer a preventing approach to a repairing approach it is because I worry that by the time I am old it will be to late
to do anything. I will have undergone so much genomic damage that my original genome would be almost mathematically impossible to regenerate.

In a previous discussion I said that problem is not that we need to make life immortal. The machinery of life is immortal and forever replicating and evolving. The germ line forever changes, recombines. Somatic cells are also undergoing these changes but to maintain the individual they are subject to cell death and telemere shortening yet viral inserts in eukaryotic DNA specifically deactivate the cell death pathway and the immune system counter attacks.
When these mechanisms fail the individual faces death yet even of a consequence of them working the individual also eventually faces death. Ironically the death of the individual occours because the machinery of life is immortal and forever trying to have have sex.

The problem is not how to make life immortal but how to maintain the individuals genetic code or at least to seamlessly maintain the consciousness of the individual while his or her genetic code changes over time.

How does SENS plan to make stem cell therapies patient specific?

I see preventing and repairing damage as an energy investment. Organisms can invest energy into maintaining somatic cells and they can invest energy into passing on germline cells. It is quite possible that we can use external energy sources and digital methods of storage (genetic information databases) to maintain the information needed to rebuild our somatic cells.

If tomorrow I could have an autologus bone marrow transplant and have the genetic information taken from my Mesenchymal stem cells to be sequenced and stored electronically in a database for later reconstruction I would feel a lot more confident. According to Craig Ventor we might have synthetic eukaryotic cells in a decade. People today need to know that we have preserved the genetic information that will be used to make them patient specific.

Edited by caston, 07 August 2007 - 02:36 PM.


#22 maestro949

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Posted 07 August 2007 - 03:16 PM

And yet, today, we can replace essentially a person’s entire immune system with a bone marrow transplant.


Ouch. A $900 trillion cost if every person were to do this only once ($150k * 6b). Combine that with the risk of death, having to find a suitable donor and the 45 day hospital stay, this just isn't a practical solution, even at a fraction of the cost. This is a perfect example where it probably makes a wee bit more sense to figure out the immune system and it's integration with the other systems at a more detailed level and see if we can make some more affordable tweaks that are more feasible to implement on a wide scale. This wide scale implementation requirement is necessary as society will reject longevity solutions if it's limited to only the wealthy.

Organ transplant


To mimic them we need to understand their function and biochemical inputs / outputs and interactions in detail. Artificial hearts get you what, 18 months after a few decades or research? Not nearly enough for life extension purposes and not on a very good trajectory :(. For the organs involved in the endocrine system we absolutely need to understand the hundreds of hormone levels and their various interactions. Systems biology to the rescue. Better informatics, statistical and modeling tools for the biologist will help here.

The great news is that there are remarkably few fundamental types of damage.


Fundamental yes, but hundreds of subtypes buried at many levels and no guarantee that a handful of solutions will work across them all. Many cancers, protein misfolds, amyloids, tissue damage, point mutations, misaligned transcription factors and metabolic dysfunction. There is probably more we haven't even detected yet. All damage at every level needs to be continuously be fixed as quickly and effectively as possible for economical and widescale longevity to emerge. Fixing some of the damage for some of the people isn't viable.

#23 caston

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Posted 07 August 2007 - 04:03 PM

Ouch.  A $900 trillion cost if every person were to do this only once ($150k * 6b).  Combine that with the risk of death, having to find a suitable donor and the 45 day hospital stay, this just isn't a practical solution, even at a fraction of the cost.  This is a perfect example where it probably makes a wee bit more sense to  figure out the immune system and it's integration with the other systems at a more detailed level and see if we can make some more affordable tweaks that are more feasible to implement on a wide scale.  This wide scale implementation requirement is necessary as society will reject longevity solutions if it's limited to only the wealthy.


So what if we cure ageing but only Bill Gates can afford it when it first becomes available? Don't you think entire face of philantrophy will eventually be transformed by their example?

Whatever politcal and economic method of cooperation leads us to cure ageing still cures ageing!

The way I see it at the moment it's about 150k to get your genome sequenced? The market will expand and the price will come down. People need to be able to salary sacrifice life extension therapies from their before tax incomes. This will make most of the difference as it makes sense to be able to keep productive people in the work force longer.

#24 maestro949

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Posted 07 August 2007 - 05:37 PM

Whatever political and economic method of cooperation leads us to cure ageing still cures ageing!


I don't disagree but the science still needs to be done to make aging intervention a reality which means funding. Lots of funding. The above example was simply to illustrate that having a fix for everything doesn't necessarily equate curing aging as the economic reality of applying the therapies en mass is a necessary consideration in engineering the interventions.

#25 maestro949

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Posted 07 August 2007 - 05:52 PM

Please give an example of this that would not be fixed by repairing damage in general. If the damaged pathways is within a certain percentage of a population of cells, those cells should be destroyed, and replaced. Fixing all these cells individually strikes me as harder. If you can prove me wrong, you’d make me a happy man. If you’re speaking about the endocrine system I’m of the opinion that if you can repair the damage in it’s constituent parts it would probably work out.


What if the damage is not just those identified by SENs but also small and subtle changes in the transcriptome across all or most cells in the body. I'm not against reengineering an entirely new body to plunk my white and grey matter into but I'd rather hold off on that as long as possible.*

* though part of me wonders whether it might be easier :)

#26 John Schloendorn

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Posted 07 August 2007 - 06:29 PM

Deep down inside I will tell you the real reason why I prefer a preventing approach to a repairing approach it is because I worry that by the time I am old it will be to late to do anything.

This is exactly one of my reasons to prefer a repair approach ;-)

#27 niner

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Posted 07 August 2007 - 06:35 PM

It'll take machine learning and some heavy duty statistical analysis to go beyond a certain level of complexity but I believe it's doable. We need to assemble a hardcore team of theoretical mathematicians, statisticians, comp science PhDs, biologists, chemists, lock them in a room and not let them come out until they have a set of specifications for the tools they need and a roadmap for building such a model. 

I get the sense that because we don't understand all of the complexity now, that you're saying it's beyond the understanding of mere humans. I may be misreading you here, but I'm not so sure that is true.

I lived through a period in the pharmaceutical industry when the complexity of genomics, combinatorial chemistry, the then-new concept of molecular diversity, and high throughput screening led for calls to assemble hardcore teams of theoretical mathematicians, statisticians, comp science PhDs, biologists, chemists, lock them in a room ... and the results were largely worthless. It turns out that most of the developments of any value from those efforts came from people who were trained in multiple fields. Specifically, the best results were had from people with their main training in chemistry and biology, who were secondarily skilled in statistics and IT. Mathematicians, statisticians, and IT people who lacked domain knowledge in the problems at hand tended to waste time due to naive assumptions about chemistry and biology. There were certainly incidences of stat/IT people working closely with chem/bio people where good things got done, but where things worked well, things tended to be driven by the chem/bio people.

#28 maestro949

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Posted 07 August 2007 - 07:52 PM

I get the sense that because we don't understand all of the complexity now, that you're saying it's beyond the understanding of mere humans.  I may be misreading you here, but I'm not so sure that is true. 


Not so much that it's beyond our understanding as we should be able to zoom in on any one component and understand what is going on at any level, right down to the physics driving the chemical reactions or proteomic function. Rather, I think we will not be able to do much prediction on our own with all of the numerous variables and interactions without much assistance from some rather sophisticated tools that hide much of the complexity. An analogy would be the evolution of software language generations in the computer science space. First generation through fifth these have gotten easier to develop with due to the evolution of layers of libraries that hide the lower level complexity. The results have been an increase in the number of people that can write software. Science needs a similar revolution such that chemists have user friendly physics engines and tools to work with biomolecules, biologists have user friendly tools to work with chemical reactions and complex biological data sets from the emerging -omics spaces and high-throughput lab toys.

I lived through a period in the pharmaceutical industry when the complexity of genomics, combinatorial chemistry, the then-new concept of molecular diversity, and high throughput screening led for calls to assemble hardcore teams of theoretical mathematicians, statisticians, comp science PhDs, biologists, chemists, lock them in a room ... and the results were largely worthless.


I'm not surprised. The efforts for such toolsets are larger than what a pharmaceutical is willing to invest the development dollars to design, build and support. They do buy and build tools but the scale I'm thinking is much larger and more integrated across the various disciplines and includes the datasets from the various subfields of biology & chemistry. Startups that have tried to build these tend to fold up or get snapped up by pharmaceuticals. Academic efforts show promise from time to time but lack the funding.


It turns out that most of the developments of any value from those efforts came from people who were trained in multiple fields.  Specifically, the best results were had from people with their main training in chemistry and biology, who were secondarily skilled in statistics and IT.  Mathematicians, statisticians, and IT people who lacked domain knowledge in the problems at hand tended to waste time due to naive assumptions about chemistry and biology.  There were certainly incidences of stat/IT people working closely with chem/bio people where good things got done, but where things worked well, things tended to be driven by the chem/bio people.


Interesting. I see a similar problem in business related fields for even small scale efforts. It's common for software engineers to mis the mark when lacking the domain expertise for the systems they are designing. If the up front requirements are insufficient, the projects rarely make their target dates and even the sought after functionality.

The only way I really see large scale systems biology emerging is for the datasets, standards, and toolset development to be open combined with some type of international government funding to accelerate the process. The way money is doled out in little chunks doesn't work for this type of effort.

#29 Brainbox

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Posted 07 August 2007 - 10:16 PM

For the risk of being very naive... but please read on...

As far as my understanding of biology goes, the analogy with systems (software) engineering is only partially applicable. In biology, functions do not always correspond to physical entities in the body, like the immune system that is formed by a collection of cells that are all over the place.

Furthermore, the body consists of primary functions that form the functionality of a human being, like ability to speak, think, feel, move, etc. The physical entities that implement these functions seem to be quite modular and "locatable". Sensors, actuators and central computer, interconnected by nerves for data and manipulation. Secondary functions for support, like lungs, digestive tract for energy supply. Tertiary supportive functions for shielding and damage repair of threats from outside. Etc.

The more supportive a function becomes, the less it can be identified by a simple physical entity in the body, i.e. the less it is "locatable". The "locatable" physical entities in the body that host the primary functions do have very complicated interfaces to the distributed supportive functions. The physical interface that is implemented by the blood flow through blood vessels seems to be quite simple, but the logical or functional interface between the supportive cells and the cells that form the primary entity is very very complicated. In fact, the supportive cells do not interact with the aggregated entity, but they interact with the cells that constitute an entity at the level of the cell, regardless of what entity that cell belongs to. (Simplification) Probably even more aggregation levels are relevant in this equation.

I think that this might be the main reason that systems biology at a white-box approach is ridiculously complicated. It seems almost impossible to isolate a function or physical entity (depending on your perspective) from the body and make it work in a simulated environment to test it. Or to make a model of it. Ok, it might be possible to make a hart beat outside its natural environment, but not with all the interfaces that matter, especially the (functional) interfaces that are used by the complicated support functions. What seems to be possible is to test at the level of cells (in vitro), but research of this nature can only be of initial exploratory value due to the fact that it is not sufficiently representative for a full functional environment.

In a reengineering attempt, using a bottom-up approach, we could first model the interaction of a cell with its environment. After we know that, we could go a level higher in hierarchical structure. Etc. Given the high amount of types of cells that all behave differently and the huge amount of functional interfaces a cell has, this will be a huge (impossible) job. A top down approach, starting with a black-box model of a being, is also impractical, since the supportive functions are not visible outside the box. And it are the supportive functions that are our main goal if we want to investigate the aging process.

Where to start? How to reduce the ridiculous complexity?

Would it be possible to select only certain aspects of the behaviour of cells in its environment by selecting only the interfaces that matter for the aging process to test / model these? Do we even have sufficient knowledge to make such a selection?
Would it be possible to start somewhere in the middle of the structural hierarchy? Like taking a simple generally representative organ, virtually remove it from its real environment and test / model all its (functional) interfaces? Thereby using a high level of abstraction as a reduction of complexity?
Or use both appraoches combined?

I think we will not be able to do much prediction on our own with all of the numerous variables and interactions without much assistance from some rather sophisticated tools that hide much of the complexity.

Wouldn't a clever selection of abstraction level be the key? How else would it be possible to hide unknown details that form the complexity?

Edited by brainbox, 08 August 2007 - 07:07 AM.


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#30 caston

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Posted 08 August 2007 - 02:46 AM

This is exactly one of my reasons to prefer a repair approach ;-)


So are you planning to sequence your genetic information for inclusion in a database where it can be stored digitally then backed up to DDS-5 and archive quality optical discs and kept in a dark room?

Until I can do that the only copies of my code exist in my body. I expend a lot of energy maintaining that code. I'm not about to stop spending energy maintaining that code just because I assume that in years to come I can hot-swap it with the code from someone else's stem cells.

Maybe understanding metabolism is like understanding data corruption. Sure by all means use a well ventalited dust guarded case, good quality UPS, PSU, parity RAM, decent quality motherboard chipsets, a HD with less magnetic wobbles and an optical drive that minimises them as well, not to mention stable software and drivers and anti virus / anti malware sofware,
hell you can have the biggest ass RAID array in the world but no matter how much effort you put into it doesn't eliminate the need for a backup procedure.

After that we need to know how to restore data and we need to know what data needs to be restored or will soon need to be restored.

Edited by caston, 08 August 2007 - 03:26 AM.





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