96 replies to this topic

[Prometheus]

Agreed, Arne. Fixing damage is absolutely necessary - just like what medicine does now and has been doing - but fixing aging will require an understanding of the aging program (and access to technology) sufficient to alter it.

I think the damage people need to understand that you cant just keep on repairing damage exogenously.

I'll explain. Conboy et al showed that old-age muscle stem cells that reached a level of dormancy in an old host could be reprogrammed into activity when transplanted into a young host. She also showed what was the intrinsic factor that drove potentially viable stem cells into dormancy, which was a secreted molecule, TGF-b, either by blocking the protein with antιbodies or its transcription with RNAi. In essence, she showed that old stem cells in an old body dont assist in regeneration but old stem cells in a young body do. Ergo, young stem cells in an old body will struggle.

The damage theory people would say to transplant young stem cells in an old body. There would be benefit but as the body gets increasingly older there will be diminishing returns from stem cell treatments because the surrounding environment they are transplanted into is sending powerful suppressive signals such as those from TGF-b. We see the same thing with hormone treatments, diets, etc. You inject a hormone but the receptors for the cell to respond to it are no longer being expressed. You stick on a superb diet but the waist softens and the muscles sag. Whilst there is a transient benefit inevitably the subject succumbs to the aging program.

The program people would say to find out why TGF-b increases with aging. What purpose does it serve? Purpose is important - does it suppress risk for another pathology? If so, what is the other physiology, genetic regulation and key molecular players there? What is the upstream regulation and how can we modulate it to allow stem cells to retain a youthful regenerative function.

The damage people may then say, so what? OK, you've got a few extra working stem cells - big deal. You haven't solved aging. But wait, with more stem cells able to conduct their repair and maintenance activities, the tissues and organs in the body continue to function and repair damage endogenously. Glands continue to pump hormones, the thymus and bone marrow produce youthful levels of immune supporting cells, the vascular system remains elastic as does the dermis.. Of course it's just a hypothesis, but the first part of it has already been demonstrated by Conboy.

[VidX]

I'm not a scientist (just an enthusiast) but I try to think about this from evolutionary standpoint. Sorry for my english in advance.

IN MY HUMBLE OPINION

It's all about DNA and being alive. being alive to pass your DNA. DNA is in every cell, and all the cells work together to keep the body alive long enough to pass it's DNA. Different life forms need different amount of time to accomplish that, they differently manifested as a complex forms of life at some point from the same ancestor and started their journey as separate species. 

AND - Evolution DOESN'T program anything (to say it's "programmed" somehow) it's a RESULT, result of how these biological systems work. And they work in a way, directed towards Staying alive. It's all about individual AT FIRST, and the specie goes after that. Evolution doesn't "care" if some specie will survive, individuals of these species care, that's what fuels further evolution. There wasn't somebody to decide what's BAD  or what's GOOD for a "specie"  as a whole, it was an individual trying to stay alive and a mechanism which let further evolution to happen, that let an individual to improve himself.  To be more accurate -  that let a DNA to improve itself to be more effective at staying alive. And the community  of such an Ego/self interest driven individuals is what forms a specie, or in our case - even society. Individuals search for a way to form an effective community to keep THEMSELVES alive,  NOT to keep everybody alive, but THEMSELVES at the first place. 



SO - If individual of some specie (say homo-sapiens) is wired the way is wired, that means there was a process that led to that final "product". "Final" in theory, we all know it's changing, evolution is happening. I'd look at that "product" as a car. There are stages that happen automatically. Like in a BMW factory..robots/humans make parts, then they are assembled, the whole structure, the engine, car is on the way, but it's unfinished until final screws are put, PC is programmed and all the final things tweaked to work propely. THEN - a person buys it (let's call it consciousness. In self sustaining machines, that are human body, it's there from the start, but it's just an analogy) and starts the exploatation of that final product the way it was intended to be used.

 THAT'S how human body is formed - semi automatically with "programmed" information in advance to manifest a fully working human body ready for exploatation, capable to pass that DNA (it was more effective to pass it from body to body, then to somehow "create" a perfect body from the start which doesn't die. It's a nonsense. Evolution is a product, so it can't "program" anything, that's the life forms who programmed themselves in a certain way. And in this case they figured out an effective mechanism to keep DNA alive - form a new life and pass it on as far as possible and keep tuning these abilities to stay alive, to be more effective at it.). There actually couldn't be any ADVANCE programming on what a body needs to "do" after it's "wired", it's like predicting a future. So it start's to act pretty chaotically after certain damage is done, and it seems that the range is very similar for all individuals, BUT it can vary, and it varies, depending on a lot of factors. The external ones shows that it CAN be tuned, it's just not efficient enough (lifestyle, sport, good eating habits.. they can help you to use that machine as effective as possible, but CONSCIOUS changes in cellular level is what matters the most. And you can't "reach" it with a vegetable or running every morning..). Well drugs are efficient, they work on  a deeper level, but it's not deep enough. And the purpose is different - to repair the serious consequances of a damage not the arising damage itself. 



2nd SO - There wasn't enough time to appear some mechanism to repair all the damage that has been done from the moment "car" was fully built and runnin'. It was crashed faster then it was beneficial to create these mechanisms. Hell - people bought a new one faster then the old one became "old", and few that was exploatated long enough - they were too few to inspire suh a regeneration in a whole "market" of cars. 

 THAT'S why some people managed to keep repairing their old classic cars to keep 'em alive as long as they wanted (copyrights goes to A.De.Grey). Cars that were a manifestation of programming a priori, but there was no further programming to determine what should "happen" next, there just wasn't such a need. Cooling, oiling, eroor check systems in car PC were established, but that's pretty much all.

 I think that a car is even a more difficult creature in some sense, as the parts aren't "wired" in genetical pathways, and you won't repair all the rust just by repairing one rusted part, you'll need to change everything manually. While body is pretty much made of the same material, core cells, has central pathways of "communication" (stem cells forming an "injured" engine, etc..).. 





That's why death IS NOT programmed, it couldn't be programmed, because INDIVIDUAL is what matters, and INDIVIDUAL made an evolution happen just because he wanted to stay ALIVE as long as possible, and individual is that ONE CELL in some sense (as one cell is enough to read all the information about given animal of some specie) that want to stay alive. 

AND - of course there exists a process (certain genes get's activated, as FUSES, systems get shutdown, chain reaction begins..) of "aging", it's the same process of a car getting old. The diod lights up, informing there's something wrong with a temperature of an engine, then cooling is increased, cooler starts to overwork, it breaks after some time, RPM decreases, chaos starts to happen. Car "wants" to ride, driver wants it to ride, he tries to keep it goin', BUT there's a point where no more "fuses" exists, it just rolls further SOMEHOW until some crucial part fails and everything STOPS DEAD (and repairman says - "Well.. thersn't much we can do anymore..you know - your car is too old, too damaged, you'll need much more then usual car service to revive it..") it starts to deteroriate, get's towed to a junk yard, GAME OVER.



3rd SO - we need to "finish" the work our ancestors started long ago. We need to make further evolution to happen, WE are the PROGRAMMERS, we allways were and it's pretty obvious that we don't want to create a "program" which get's our bodies old, that'd be Evolution backwards, pretty ridiculous eh? We are clever enough to start thinkin about repairing that damage and keeping DNA alive as it is without the need to pass it further, as it was the first and most important goal of the most primitive life form - TO STAY ALIVE, to eat, to get the energy and TO STAY ALIVE. 



 Let's finish it

Edited by Divine, 02 March 2009 - 01:47 AM.

[Prometheus]

Divine, your layman interpretation would be reasonable if there were no such things as immortal lifeforms already in existence. Have you thought about this when considering your car metaphor? Its not just that some cars wear faster than others, its that some cars don't seem to wear at all.. Even more bizarre is that there is one car component which never wears and is passed on from car to car..

You - and all livings things - originate from a biologically immortal cell line (the germline) - it does not age. From that cell line other cells differentiate, which unlike the germline, appear to be designed to fail.

This is as simply as I can put it.

The important thing is that this interpretation is not self-defeating, i.e. it is not an acceptance of the inevitability of aging, but rather presents the possibility that by understanding the nature of the aging program we can alter it and achieve a solution to the aging problem. In my view, the damage approach, whist very important for extending lifespan, ultimately will fail at a very advanced age.

Both the damage and program approach are complementary to extending lifespan indefinitely.

[VidX]

I'll do some research/recheck on what's known about immortal life forms as I can't remember at the moment.

"Even more bizarre is that there is one car component which never wears and is passed on from car to car.." - Are you talking about DNA?

"From that cell line other cells differentiate, which unlike the germline, appear to be designed to fail." - That's just my spontaneous speculation, but MAYBE that's because they are just the "tools" of a second importance to make sure the passing of the first ones, and individual organism developed an extra repair capabilities for these. Actually, if I'm right - sex cells have such an additional mechanism, and while they don't "age", they still accumulate some damage (correct me if I'm wrong). 

SO - MAYBE that's another possible cause of the change in gene expression. "fuses" start to fire off when they "sense" that germ line cells accumulated too much (even if it's just very little, keeping in mind the importance of these) of a damage and that means that passed DNA won't be the quality one. 



Well I feel I need to do a lil' more research on this one. Anyway, I think we should ask - How is this/that relevant to individual in an evolutional terms? I highly doubt an actual "ageing" program exists, just because it should've arose on the way somehow, and if individual organism tried to stay alive - this gets pretty contradicting. Orginsm staying alive, trying to pass the DNA and developing a mechanism that gets him old. Ofcourse maybe I'm missing something, but I'd think a more possible outcome would be a "finished" machine tries to procreate as much as possible and there's a point when entropy/damage/wear 'n tear takes place to a crucial parts (and less crucial, who has less effective repair mechanisms) and it's no longer capable of resuming an efficient job so some "fuses" starts to fire and shut it down, to keep him out of the procreators pool. But then again - it's about individual, NOT about specie.. It's confusing.
There must have been some mechanism that determined of HOW LONG an individual should be able to procreate as that's what matters in the first place. And keeping in mind that there's no outside source of influence/programmer, the internal workings of that organism are what matters. I guess hormones start to shut down as the first sign of person getting "old" (all other changes seems to be pretty much damage/lack of proper regeneration based if we talk about common signs of mature age, like pains in joints, poorer sight, graying hair, not about serious disseases)..




"but rather presents the possibility that by understanding the nature of the aging program we can alter it and achieve a solution to the aging problem. In my view, the damage approach, whist very important for extending lifespan, ultimately will fail at a very advanced age." - I agree completely, it'd be perfect solution to have an intervetion which'd provide a super accurate repair mechanisms or other needed mechanisms, which would sustain a body in a fresh state, but it seems that "Damage repair" way is the way to go at this moment (while trying to understand the big picture, to solve that puzzle).

Edited by Divine, 02 March 2009 - 04:14 AM.

[astrout]

I think that it is wrong to argue how things work based on our understanding of the evolutionary process. I say this because the evolutionary process is not a logical process in that it only punishes bad behaviors, so good mutations prevail. If we assume that only a small set of species actually have developed the immortality genes at this point (a few species of jellyfish have been discussed) then the other species didn't un-develop immortality, they merely grew from species which did not have the immortality gene which grew from others which were similar. I beleive if you look at species as they become more advanced (humans near the top) you will find that their (in general) life span is longer (with obvious exceptions for very slow living species). It stands to reason that the most complex beings have the benefit of the most evolutionary enhancements and that the less complex beings (bacteria, viruses, yeast, etc) will have the benefit of fewer. Bacteria and viruses have very short lives, but they thrive quite well due to other adaptations. Would you say that the short life span of bacteria should never exist? Now, Bacteria may be a bad example because they reproduce by cell division, so in that sense they don't die. I guess my point is that life span differs so greatly in species that to say that they would all be immortal if it were better for survival might be giving evolution too much credit. It certainly does not produce the ideal all the time, it just provides a mechanism for advancement.

[Prometheus]

Anyway, I think we should ask - How is this/that relevant to individual in an evolutional terms? I highly doubt an actual "ageing" program exists, just because it should've arose on the way somehow, and if individual organism tried to stay alive - this gets pretty contradicting. Orginsm staying alive, trying to pass the DNA and developing a mechanism that gets him old. Ofcourse maybe I'm missing something, but I'd think a more possible outcome would be a "finished" machine tries to procreate as much as possible and there's a point when entropy/damage/wear 'n tear takes place to a crucial parts (and less crucial, who has less effective repair mechanisms) and it's no longer capable of resuming an efficient job so some "fuses" starts to fire and shut it down, to keep him out of the procreators pool. But then again - it's about individual, NOT about specie.. It's confusing.
There must have been some mechanism that determined of HOW LONG an individual should be able to procreate as that's what matters in the first place. And keeping in mind that there's no outside source of influence/programmer, the internal workings of that organism are what matters. I guess hormones start to shut down as the first sign of person getting "old" (all other changes seems to be pretty much damage/lack of proper regeneration based if we talk about common signs of mature age, like pains in joints, poorer sight, graying hair, not about serious disseases)..

Evolution can be likened to a process of hypothesis testing. Each time a change in the DNA is introduced (the hypothesis) it is tested: does it confer additional fecundity (potential to reproduce)? If yes, it is passed on. If it makes no difference it is also passed on, but obviously to less numbers. If no, it does not get passed on. Using this system you can then test for yourself if extended lifespan would be a beneficial trait.

Supposing, for example, a trait that enables a doubling of lifespan but at the cost of a similarly extended pubertal onset manifests in a species. What do you think the consequences would be on that species' survival?

[JLL]

Evolution is not "concerned" with the individual but with genes being passed on. The body is just a vessel for the genes. Therefore it would b entirely possible for the genes to choose vessel that self-destructed, if such a vessel was somehow beneficial for the genes. I don't see any evidence that this is so, but the argument that evolution wants to preserve the individual is flawed; the individual is important only insofar as the individual can continue to pass on the genes.

[Prometheus]

Evolution is not "concerned" with the individual but with genes being passed on. The body is just a vessel for the genes. Therefore it would b entirely possible for the genes to choose vessel that self-destructed, if such a vessel was somehow beneficial for the genes. I don't see any evidence that this is so, but the argument that evolution wants to preserve the individual is flawed; the individual is important only insofar as the individual can continue to pass on the genes.

Following from your 'genes in vessels' metaphor, the frequency with which genes 'hop' from vessel to vessel determines their rate of evolutionary adaptation. Therefore, not staying around a vessel for too long would be advantageous.

[VidX]

" beleive if you look at species as they become more advanced (humans near the top) you will find that their (in general) life span is longer (wit" - It seems it's more related to selective pressure/predators for certain specie. I mean - the less pressure/dangers from the enviroment a specie has, the longer it lives. For ex. - elephants - giant animals, but lives almost as long as humans, and some even longer, like 80 years.. Does that provide a clue, that MAYBE these short lived species direct all their energy toward reproduction as fast as they can, so there's no energy/time left for developing a longer life span through evolutionary process?

Talking abou jelly fish, I'm not sure of it's position on evolutionary ladder, but it seems that it has very few dangers from the enviroment. BTW - they are immortal ine a DNA sense, not in actual individual jelly fish. I mean - they revert to polyp state, then bud again and some of the polyp dies, but new buds become jelly fish with the same DNA. So that's immortal in some sense, but not in that we would like to be..



"It stands to reason that the most complex beings have the benefit of the most evolutionary enhancements" - That probably means - the "fittest" of them has these benefits. It's pretty logical as the main fact that they are well adjusted to the enviroment means they experienced mutations that benefit them at staying alive. 

"Bacteria and viruses have very short lives, but they thrive quite well due to other adaptations. Would you say that the short life span of bacteria should never exist?" - I'd speculate that they are too primitive and the way they reproduce is too different to make an analogy. 

"so greatly in species that to say that they would all be immortal if it were better for survival might be giving evolution too much credit" - Maybe it just wasn't enough time to more complex organisms become "immortal" as they have much more systems to "sustain" and to keep them "fresh"..? 

BTW - If gene expression is one of the main things that changes the "behaviour" of a given organism, question is - Are they the trigger by themselves, or is there a trigger that fires them off at a certain time? And how often gene expression changes to obvious enviromental/external reasons (red an article on gene expression change just from the experienced stress in a childhood)? 



Dr Strange...> Thanks for an analogy, I'll think about it. 

"Following from your 'genes in vessels' metaphor, the frequency with which genes 'hop' from vessel to vessel determines their rate of evolutionary adaptation. Therefore, not staying around a vessel for too long would be advantageous." - But the thing is - they don't "think" what's more advantageous, they just.. "go with the flow", and that seems to be "To stay alive", as it's the first and the main factor to be able to reproduce at all for an organism.



JLL> Well.. evolution doesn't "want" to preserve anything, it's the individual that strives to preserve himself. That's a DNA that manifests it's traits throught the multicellular irganism to preserve itself. So we probably can say that all the organism is wired to preserve that DNA and therefore - himself as it IS DNA. And because it's a direct manifestation of it, it means that DNA is inefficient to preserve itself in one organism for long enough so it needs to "divide"/reproduce to try again.



BTW - just red some reptiles, like turtles and aligators have very effcicien DNA repair mechanisms, I'll make some more studuying on that to write something more, but if that's true it'd suit a model of "The less predators, the more time to reproduce, the better your repair mechanisms are"..

Edited by Divine, 04 March 2009 - 03:58 AM.

[VidX]

As I think now.. even the fact that we are searching for a way to be "immortal" it means we continue evolution towards that direction, so it'd mean that it all was going to this. We were fit enough to have an increased life span, we are getting even fitter, so we basically try to "correct" the errors nature left, speed things up and "finish" its job in some sense (DNA searchin for a way to survive and stay alive as long as possible).

It's more like a phisolophical outlook, but I just wanted to share it. Basically I can't wrap my mind around the idea of "programming" as there's no "prgrammer" outside the DNA itself (and spontaneous changes, physical laws, etc..). So it's realy difficult to accept the idea that DNA actually "programmed" itself to die as the main purpose and efforts was directed toward staying alive/avoiding the death/inmproving in various types of "fitness" to avoid that extinction.. 

Even that jellyfish, seems like they appeared pretty recent (that specie) and the fact it tries to preserve the SAME DNA (especially in stress/threat conditions) hints something. Of course it's too different from humans (and the way they reproduce) but I just try to conncect the "dots" somehow..

Edited by Divine, 05 March 2009 - 12:57 AM.

[Prometheus]

Basically I can't wrap my mind around the idea of "programming" as there's no "prgrammer" outside the DNA itself (and spontaneous changes, physical laws, etc..). So it's realy difficult to accept the idea that DNA actually "programmed" itself to die as the main purpose and efforts was directed toward staying alive/avoiding the death/inmproving in various types of "fitness" to avoid that extinction.. 

This notional distintion may help: the 'programmer' is the collection of forces directing evolution whilst the the DNA itself is the medium where the program is written and executed.

[VidX]

Basically I can't wrap my mind around the idea of "programming" as there's no "prgrammer" outside the DNA itself (and spontaneous changes, physical laws, etc..). So it's realy difficult to accept the idea that DNA actually "programmed" itself to die as the main purpose and efforts was directed toward staying alive/avoiding the death/inmproving in various types of "fitness" to avoid that extinction.. 

This notional distintion may help: the 'programmer' is the collection of forces directing evolution whilst the the DNA itself is the medium where the program is written and executed.

Well I've done more research and it just doesn't "connect" (for me). "Forces" can't really "program" anything and they doesn't "direct" evolution in any way. I mean - yes, enviroment and all that happens in it IS evolution by itself, that's the process and it's manifestation that we call evolution (we are talking about evolution of life forms of course). But if we talk about DNA as a medium for these "forces", then we are balancing near "Supernatural" type of ideas... We should not forget that DNA IS a programmer itself to a large extent. I doubt very much that envoriment actually "thinks" about "Tweaking this thing to work like that and this like that"... it get's much more complicated and evolutionary process as we understand it isn't really THAT difficult. Survives the fittest. Key word "Survives" (energy directed to survival.. how much energy any specific life form can direct towards that? It's pretty interesting "coincidence" that these who have the least predators live the longest)... 


 AND - if aging is really programmed (and I'm getting pretty sure it's just "unfinished" mechanics of regenerative mechanisms) why we get wrinkled skin even when productive age is far from it's "Finish". Is there any gene that produces "Old" skin or is it a damage that accumulates and repair mechanisms that fail after some time? Why do we start to loose sight after some time, is there any gene pathways responsible for that? No. It's the junk that causes some proteins to get stiff (and there was no time to develop natural mechanisms to repair that.. well, in some animals there was, and they seem to be doing pretty well as we know. Some type of turtles get even better reproductive abilities as they age. Basically they are getting more effective with age, not vice versa..)... 

 All the "Programming" approach fails at one simple point - Life is about Staying alive.. that's why we HAVE these mechanisms that try to repair damage, that's why we have these instincts that tries to save us from death, basically all energy of any given organism is directed to staying alive and all the mechanisms that exists in us "say" that. Though I can't really find any at least half as convincing evidence that aging is really a "program", which should be a really difficult one, 'cause creating a mechanism that "Makes" organism old is going against the basic evolution principles back in the day these mechanisms theoretically should've "evolved".. Firstly organism adapts all the traits to be more effecive at staying alive (and "save" them for future generation to be even more effective at that task) and then it starts developing ones to die? How? When? If there was not enough time to develop really effective repair mechanisms for many species at first hand? IMHO that's pretty much a nonsense...



Merely a fact that we try to find a way to avoid aging, that we developed various drugs to help body combat infections, viruses, etc (shortly - to be more "fit") shows that it all was about this from the start. The same instincts are in play. Everything we do, any activity is directed toward that goal... WE are the evolution, we try to stay alive and we came to a point where very few natural dangers exist (again - are there any "Cancer genes"? Hell no, just unfavourable mutations and failing repair mechanisms. But hey - some individuals have ANTIcancer genes. Why do they need em' if aging and death is "programmed", why to interrupt that programming with a mechanism that saves individual from a dissease that usually happens in "Old age", when he "should" die anyway?) so we can concentrate/direct our energy at creating a repair mechanisms/methods to save our failing bodies. 

Edited by Divine, 24 March 2009 - 03:14 AM.

[eternaltraveler]

You - and all livings things - originate from a biologically immortal cell line (the germline) - it does not age. From that cell line other cells differentiate, which unlike the germline, appear to be designed to fail.

seriously?

Are you honestly using a single cell line as an example of how aging must be programmed when you know:

-cell division dilutes junk accumulation to the point of obscurity. Go find me a single cell organism that doesn?t divide, continues to metabolize, and doesn?t die.

-gamete selection, and spontaneous abortion do an excellent job of selecting the very few gametes that remain genetically favorable.

-Humans are not single celled organisms. Even if our cells were completely ageless, that says nothing about whether an entire complex organism composed of 10^13th cells interacting in obscenely complex ways would likewise share this trait.. Can you not acknowledge the possibility that evolution simply hasn?t had time to deal with that?

-finally; evolution has never had a reason to even try to make mammals in general, or hominids in particular, ageless. Extrinsic life expectancy for all of evolutionary history until the last century has absolutely ensured that all by an vanishingly small minority would die before even the onset of menopause.

Chimps die before the age of 15 in the wild http://www.sciencedi...9acf20d743887ac

In captivity the same chimps live to be 60 (4 times older than in the wild). Cheetah, the chimp that was the star of ?tarzan? is reportedly still alive today at the age of 76.

We live many decades past our warranty period in the modern world. Give evolution a few hundred or thousand millennia under these conditions and our intrinsic mortality would be bound to start to catch up to our new 1000 year extrinsic mortality (risen from 40 in the last hundred-two hundred years). Please tell me why in the world evolution would have to program us to not live to be 1000 when we would be lucky indeed to make it to 50?

By the logic you are using in your programmed aging hypothesis disease susceptibility must be programmed as well, because if it wasn?t, evolution would have programmed us not to get sick. Similarly we must be programmed to die when we get hit by meteorites.

The programmed aging hypothesis was once very popular, but has since fallen completely out of favor as the evidence against it is astronomical. If you continue to hold this position the burden of proof is on you. Best of luck.

Edited by eternaltraveler, 24 March 2009 - 04:34 PM.

[JLL]

Evolution is not "concerned" with the individual but with genes being passed on. The body is just a vessel for the genes. Therefore it would b entirely possible for the genes to choose vessel that self-destructed, if such a vessel was somehow beneficial for the genes. I don't see any evidence that this is so, but the argument that evolution wants to preserve the individual is flawed; the individual is important only insofar as the individual can continue to pass on the genes.

Following from your 'genes in vessels' metaphor, the frequency with which genes 'hop' from vessel to vessel determines their rate of evolutionary adaptation. Therefore, not staying around a vessel for too long would be advantageous.

So does it follow from your idea that if there was no change in the environment the vessel lives in and thus no need for adaptation, would the advantage of 'gene hopping' vanish? Because the question of why we need to adapt in the first place remains. If the genes could just change themselves inside the vessel to better suit the environment, it's not so difficult to see how this could be more advantageous than reproducing.

[Prometheus]

@ eternaltraveller: I can see you feel strongly about programmed aging, which is not surprising for a SENS associate given that SENS is overwhelimingly reliant on ignoring the intricacies of metabolism (good luck with that! ). Anyway, the important thing is that we're all highly motivated to find a solution. You will seek your path and I will seek mine. I hope to meet you there, but if you get lost on the way just holler out and I'll give you my map - its the short cut.

[Prometheus]

Evolution is not "concerned" with the individual but with genes being passed on. The body is just a vessel for the genes. Therefore it would b entirely possible for the genes to choose vessel that self-destructed, if such a vessel was somehow beneficial for the genes. I don't see any evidence that this is so, but the argument that evolution wants to preserve the individual is flawed; the individual is important only insofar as the individual can continue to pass on the genes.

Following from your 'genes in vessels' metaphor, the frequency with which genes 'hop' from vessel to vessel determines their rate of evolutionary adaptation. Therefore, not staying around a vessel for too long would be advantageous.

So does it follow from your idea that if there was no change in the environment the vessel lives in and thus no need for adaptation, would the advantage of 'gene hopping' vanish? Because the question of why we need to adapt in the first place remains. If the genes could just change themselves inside the vessel to better suit the environment, it's not so difficult to see how this could be more advantageous than reproducing.

Genes exert their influence through phenotype and it is only through phenotype that a mutation is tested for selection and if successful gets to travel to the next generation, which is why your suggestion would be difficult to conceive of in a multicellular org where the mechanism of generational transfer cannot occur until a developmental threshold is achieved.

In any case, the *only* foreseeable way that evolution would select for increased lifespan is if the need for mutation rate decreased (i.e. a stable, non-challenging environment where population increase is not a limiting factor). Given limited resources this can never take place in nature.

[JLL]

Genes exert their influence through phenotype and it is only through phenotype that a mutation is tested for selection and if successful gets to travel to the next generation, which is why your suggestion would be difficult to conceive of in a multicellular org where the mechanism of generational transfer cannot occur until a developmental threshold is achieved.

In any case, the *only* foreseeable way that evolution would select for increased lifespan is if the need for mutation rate decreased (i.e. a stable, non-challenging environment where population increase is not a limiting factor). Given limited resources this can never take place in nature.

Well yes, but doesn't this beg the question why this is so? Why is not possible (i.e. why hasn't evolution chosen for) to mutate one's own genes which would then be expressed immediately? Is it because of random chance, or because it would be more costly, or because of something else entirely?

Also, I'm sure there's a fault in my logic here, but I can't seem to shake the thought that from the genes' point of view, wouldn't preserving the vessel (were it possible) be preferable to reproduction? If the gene is truly selfish, then merging with other genes through reproduction seems less preferable - since it's kind of like preserving a diluted form of yourself instead of the whole of you.

[eternaltraveler]

Anyway, the important thing is that we're all highly motivated to find a solution. You will seek your path and I will seek mine.

Indeed.

If someone proves me wrong by curing aging I don't think I'd mind too much

[VidX]

In any case, the *only* foreseeable way that evolution would select for increased lifespan is if the need for mutation rate decreased (i.e. a stable, non-challenging environment where population increase is not a limiting factor). Given limited resources this can never take place in nature.

Well it seems you support the idea of "The less enviromental dangers (need to be even more fit)" the longer the life span. That's what we see in nature. But given that evolution doesn't "select" anything, as it IS the manifestation of the processes that happen, we can guess that organism got more effective at improving it's own repair mechanism to stay alive (as the internal wear/tear seems to be a second threat to ones life after natural/enviromental dangers. And it's very logical that in no way there could have been a "Perfect" repair mechanism from the start as it evolved by the process of a natural selection and got more effective every time. Or at least - was supposed to get...). 




JLL>Exactly. How a "selfish" genome can evovle a "death" mechanism when all the time he tries to do a vice versa? I mean - programming theory goes against basic evolution principles. If we have one ancestor, different species with different mutations, different fenotypes, different way of behaviour in enviroment, different enviroments, it's pretty logical that as they all started from the same "base", just the lucky ones managed to have a longer lifespans as they just were more effective on the long run (and this allways was a main factor that counts in evolution game). There's no "canons" written that immortality should've arose if it would've been beneficial as the evolution is still happening, and as we know - some species show major  signs of non aging and extra long lifespan abilities)..



As Ocamas Razor proposes - the more simple answer is usually the right one. IMHO development of a human organism we have now is as far as process've got to go. It has "instructions" of how to behave till certain point (as it usually was all that counted as individuals were dead long before significant senescence) and what happens after that is a simple entropy/chaos which can seem like "controlled" shutdown because it's not an instant crash (usually) but a somewhat predictable fail (like in an old car, you can predict what's possibly going to happen after a certain amount of miles)... 

Edited by Divine, 26 March 2009 - 02:20 PM.

[Prometheus]

Why is not possible (i.e. why hasn't evolution chosen for) to mutate one's own genes which would then be expressed immediately?

This does happen all the time with unrepaired DNA damage where, for example, tumor suppressor genes are switched off and affected cells are driven down a tumorigenic lineage. I think what you're suggesting, however, is a global change in DNA that affects a multitude of cells concurrently. This also happens but rather than DNA sequence alterations the changes are epigenetic (DNA/chromosomal methylation, chromosomal acetylation, etc).

Also, I'm sure there's a fault in my logic here, but I can't seem to shake the thought that from the genes' point of view, wouldn't preserving the vessel (were it possible) be preferable to reproduction? If the gene is truly selfish, then merging with other genes through reproduction seems less preferable - since it's kind of like preserving a diluted form of yourself instead of the whole of you.

Think in terms of implementation - it is much, much easier to modify a single cell (i.e. a gamete) which goes on to become a multicellular system of trillions of cells which harbor the same modification rather than seek to modify trillions of cells in the same way *at the same time*.

Edited by H@rrY, 26 March 2009 - 02:22 PM.

[Prometheus]

As Ocamas Razor proposes - the more simple answer is usually the right one. IMHO development of a human organism we have now is as far as process've got to go. It has "instructions" of how to behave till certain point (as it usually was all that counted as individuals were dead long before significant senescence) and what happens after that is a simple entropy/chaos which can seem like "controlled" shutdown because it's not an instant crash (usually) but a somewhat predictable fail (like in an old car, you can predict what's possibly going to happen after a certain amount of miles)...

Yeah, that's one way of looking at it. Leonard Hayflick thinks of aging like that, likening it to the wear and tear of an old car..

From my vantage, however, when considering the numerous molecular clocks, which seem dedicated to downgrading regenerative processes over time, the damage appears to be a consequence of a designed repair inhibition. And by designed I mean not actually designed to fail but designed to do something where failure is coupled. That something, according to my reading of the research is related to evolution and more specifically to the rate of evolution.

[VidX]

Yeah, I understand where are you coming from, but what puzzles me at that case is - How that "rate" is determined? I mean - there's no outside force that we know, which could "monitor" certain specie and decide how to "adjust" certain variables AND on the other hand - evolution (to put it simple) is a result of inner workings of a given individual, merely spontaneous changes and and other reactions that works how they works. Unless there's something "programmed" on every new offspring genome of how efficient was his parents and adjustments are made, but it's just my speculation, I'm not really aware about any of that, though even the idea of something like that appears super complicated...

p.s. - couldn't it be that the "Rate" itself is a result? I mean - the more dangers a specie has, the less time to develop effective repair mechanisms, the shorter their lifespan is, the rate of the death is faster and so it goes.. And if death and the high rate of "evolution" (change) would be the way to successful evolution (what ironically leads to a longer life) wouldn't the species on the lower stairs of evolution have a very long life spans (as they would've got very effective at survival)? Or then -  what does it mean - "Rate of evolution"? Where that rate should lead if not to an increase of an individual life span?

I'm not sure if I'm clear enough, but I'm in a hurry right now, so I hope you'll get the idea.

Edited by Divine, 26 March 2009 - 03:35 PM.

[Prometheus]

successful evolution = the best breeders (because they're the ones that pass on their genes) [[makes you wonder why the introverted geek or gay genes manage to propagate ]]

think about: what negative selection factors you would need to remove in order for long lifespan to be a positive selection mechanism

[Prometheus]

Whilst we're on the topic of evolution and selection, does anyone here have an interest in archaeology or anthropology and would they know about the reduction in brain size that has been occurring in the last 10,000 years in Africa, Europe and Asia? I recently came by this information and find it most intriguing in respect to selection. Given that brain size is generally associated with neocortical mass = higher brain functions, could it be that deep thinkers, dreamers/visionaries who were out of sync with emerging sociocultural hierarchies associated with increased population were selected against?

[JLL]

Whilst we're on the topic of evolution and selection, does anyone here have an interest in archaeology or anthropology and would they know about the reduction in brain size that has been occurring in the last 10,000 years in Africa, Europe and Asia? I recently came by this information and find it most intriguing in respect to selection. Given that brain size is generally associated with neocortical mass = higher brain functions, could it be that deep thinkers, dreamers/visionaries who were out of sync with emerging sociocultural hierarchies associated with increased population were selected against?

I know it's going to come out anyway so I'm just gonna throw it out there: the agricultural revolution?

[VidX]

successful evolution = the best breeders

- But doesn't that include immune system, good overall health and  all other properties that help to stay alive ('cause first instinct is survival, if it's fullfilled then reproduction follows..)?  

think about: what negative selection factors you would need to remove in order for long lifespan to be a positive selection mechanism

- I think "Negative" "Positive" is pretty relative here, as the mechanism just works how it works and it works towards preservation of individual (or so it seems).

[Prometheus]

Whilst we're on the topic of evolution and selection, does anyone here have an interest in archaeology or anthropology and would they know about the reduction in brain size that has been occurring in the last 10,000 years in Africa, Europe and Asia? I recently came by this information and find it most intriguing in respect to selection. Given that brain size is generally associated with neocortical mass = higher brain functions, could it be that deep thinkers, dreamers/visionaries who were out of sync with emerging sociocultural hierarchies associated with increased population were selected against?

I know it's going to come out anyway so I'm just gonna throw it out there: the agricultural revolution?

hmm.. not only, carbs = aging, but also carbs = dumbing down? Perhaps. I was thinking more on the behavioral consequences of an enlarged neocortex in a society where brutality = success..

[JLL]

hmm.. not only, carbs = aging, but also carbs = dumbing down? Perhaps. I was thinking more on the behavioral consequences of an enlarged neocortex in a society where brutality = success..

One could be brutal and have a large brain, no?

In any case, while your idea is interesting, I think it's perhaps a more complex one than is needed to explain variations in brain size. I think the agricultural revolution hypothesis has at least some merit, because our brains started getting bigger when we started eating a diet high in meat and fat; before that, when it was more plant-based, our brains were smaller. Then when it became more plant-based again, our brains have gotten smaller. Very similar to the changes seen in the average height of man, unless I'm mistaken.

[Prometheus]

One could be brutal and have a large brain, no?

It depends on where the enlargement is located. Neanderthals had an enlarged occipital bump, a feature also found in modern Aborigines in Australia and believed to be associated with their demonstrated superior spatial and visual capabilities. If the frontal lobes, on the other hand, were enlarged, one could anticipate superior planning, visualization and judgement of consequence. Frontal lobe activity is also associated with social skills, abstract and mathematical reasoning and spiritualism. What we may define as ethical and restrained behavior has been shown to be associated with this area based on the consequences of injury in the frontal lobes. I would argue that a humanoid with exaggerated frontal lobe activity would be unlikely to be as aggressive or impulsive. On the contrary, we would likely see a very empathetic, sensitive and deeply thoughtful mind - totally incompatible and very much at a disadvantage in those times.. They would not have stood a chance.

[Mind]

Researchers suggest that misrepair is a significant cause of aging. Just wondering if this is a bit of semantics. There seems to be a fuzzy line between damage and "misrepair". It also sounds a bit like Vijg's genetic drift theory, after all, doesn't misrepair result in a slightly different DNA coding.

Still, if misrepair is a significant cause of aging, then how do we fix it? The SENS approach of getting rid of malfunctioning cells?

Two main theories of aging have dominated thinking in this area. On the one hand is the argument that aging is regulated by our genes, an idea that is backed up by various studies showing that some genes can dramatically increase lifespan (if you happen to be a nematode worm, for example).

On the other is the notion that aging is the result of the accumulation of various faults on the cellular and molecular level, caused by environmental factors such as free radicals and molecular cross-linking.

In reality, most researchers think that both mechanisms play an important role.

The new idea from Michelitsch and co relates to this second mechanism. They contend that the accumulation of faults on the cellular and molecular level are certainly involved in aging but are not the mechanism of aging. These faults trigger the body's repair mechanisms, which fix everything up, most of the time.

But sometimes these repair mechanisms go wrong, leaving small regions of misrepair. The new idea is that aging is the result of the accumulation of these misrepairs over time.