Why Programmed Aging is an Attractive Idea
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I noticed a post yesterday discussing a comparatively recent theory of programmed aging (which you may recall was mentioned here last year). The author, I think, hits on one reason why the prospect of aging as a genetic program - rather than a complex, messy process of decay - is attractive to those of us thinking about healthy life extension:

It seems easier to tweak the programming in a computer than to try to replace part after part in an old car that is steadily collapsing.

Sadly for would-be genetic tinkerers, the Reliability Theory of Aging and messy, complex, unprogrammed decay looks to be a much more likely model for degenerative aging in mammals.

Comments

The programmed theories of aging have been obviously wrong to me for over 15 years. Especially the ones where aging is caused by a decline of hormones. If that were the case, evolution would have eliminated aging long ago.

The theory that aging evolved as an adaptive mechanism to cancer does make a certain sense. It is in response to this that WILT (the most difficult and controversial part of SENS) is proposed as a long term solution.

Posted by: Kurt at July 11, 2005 11:14 AM

While I do agree with the reliability theory of aging, I believe that it's compatible with the possibility of programming(more directly so in shorter lived organisms.). For it to be considered programmed or selected for it's only necessary for there to be a substantially small simple gradual change that as such may occur frequently within a population, and that may lead to small simple gradual increment/improvement of the organism or its longevity, and for such not to propagate given its simplicity(say single gene mutations/duplications/etc) and given other small changes(often with little or no effect, but yet if such propagate, why would beneficial ones to individuals not?) do accumulate and propagate quite easily. Given the case of such, we can posit that it was thus selected against.

As I've read I've seen ever more hints of the presence of group selection in the real world...

Animals that mate with the losers of a duel? What do they gain? They choose to increase genetic diversity an important part of the engine of evolution, at the cost of their own success, theirs and that of their progeny....

You see brothers(in birds, turkeys I think), where one brother aids the other at attaining a mate and reproducing at the cost of his own individual reproductive success. Do to the high amount of genetic material similarity, and the SUBSTANTIAL increase in the rate of his bro's reproductive success... this strategy turns out valid and is as such present in the real world.

Even sexuality, it would seem here the individuals often give up their own capacity to reproduce by themselves, only to increase genetic diversity. For it will bestow benefits by working in group(more than one) and to the group(often after such an event progeny may be even less fit than a particular organism depending on partner, but it does maintain diversity and aids natural selection). In other cases a substantial % gives up on reproduction all -together by the fact sex-orientation's not more strongly genetically programmed, thus individuals are born whose preferences will impair their reproduction but will provide strong adult organisms capable of benefitting the group(particularly close kin, by aiding with additional resources, etc.).

Things like compressed morbidity, being fit lean, healthy and mean, and suddenly collapsing/breaking down a few years later, does not sound like progressive decay, thought it may be. IT sounds like something's forcing the decay, though there may be other reasons for this being so, as said. Those who reach 90-100+ often have impressive preservation of their mental and physical faculties, despite obvious accumulation of some dmg particularly in the exterior, and yet they often undergo compressed morbidity... why should morbidity be compressed after it's been delayed? There could be many reasons for this being so, there could be some remnant mechanism to force this, or it may simply be the results of too little redundancy in too many systems at such ages(thus any small failure could cause a cascade that would lead to other small failures, and lead to a vast deterioration in a short period of time.).

What we've to understand is that again an individual's presence and an individual's traits in an environment can be either beneficial or detrimental. As has been said in the past, if any one group of highly fit individuals were to increase longevity without bound it would be detrimental to themselves and to the group, by causing a decrease in genetic diversity. Any organism is a unit of replication, a replicator, alter some of its parameters and it's ability to replicate will be changed and this can very well be influential(such a thing is magnified by the act of replication, the passage of time) when presented with limited resources.

The reason why organisms many a times seem to mate or choose to mate with others that are seemingly less fit than the fittest possible mate available(less showy sexual-selection influenced appendages/traits, losing a duel, etc.), seems to be to increase genetic diversity and maintain optimal environment for natural selection to work on the group... even at the cost of individual and progeny fitness. It seems to me the same goes for less strength of traits like sexual-orientation, which could be exponentially stronger, and for instances when an individual compromises his reproductive success to aid another.

Right now it would seem to me like many a detriment can be passed on to the individual so-long as it benefits the local group sufficiently to outweight the costs. Thus I'd say detrimental decisions and traits for the individual but that are beneficial towards the group can spread. Limit intelligence? IF continual increase of intellect within a particular environment would compromise fitness(and in many an environment it would, given the energy costs it has, it's best to limit intelligence to the most required by the particular environment at hand and no more... even if it increased the reproductive success of an individual compared to other members, if it did not bestow comparable advantage against members of other species using less resources to obtain max possible resources out of the particular environment... the group would be harmed, and such species would be driven to extinction.), there would be selective pressure against it. Increasing longevity also has energy costs, we've seen how even single gene changes(even of a single nucleotide, iirc) can substantially and even exponentially in some species increase lifespan. WHY do such traits not spread? Why is aging not fought even when it's easy to delay it in some species given the maintainance/repair lvls they're using?


The fact is whether we like it or not, such traits most likely did appear and appeared again and again, and they did not propagate because they were most likely selected against(seeing as they seemingly benefit the individual and direct progeny, this would be due to benefits towards the group.). Same seems to go with regards to cancer simple tweaks, like duplicating some tumor suppressors(or some other stuff, memory's a bit fuzzy) would bestow substantially increased cancer resistance, given how easily so-many genes duplicate and how we-ve pseudo-genes, and so many a stuff repeated and floating about in the genome with such ease one would think that a seemingly non-detrimental trait(from what I understand neither healthspan/max lifespan or any other trait, besides cancer resistance, was measurably affected in some of these cases) that bestows such a beneficial thing as cancer resistance would easily spread too....

THAT IS... unless such would increase the possibility that individuals who're able to withstand the onslaught of aging(as has been seen in some individuals) would've even greater lifespans/or increased odds of reaching max lifespan for that particular lvl of maintainance/repair, thus benefitting at the cost of the group(by being present they take resources, all organisms must necessarily compete for resources in a world with limits on such, unless they offer benefit that compensates for this towards the group-which includes their own progeny-, they're IN EFFECT competing with others, and with the progeny of others who're often less able to compete during youth period with such full-fledged-adults. That is by taking resources they're compromising the possible max number of youths/new members that can be maintained/exist/be brought in a particular environment, and if their presence is not beneficial to such-including their own progeny- they are detrimental... both to genetic diversity and the reproductive success of their progeny... depending of the size of the detriment will be the pressure against such.)

We've seem the IMMENSE genetic similarity that exists between organisms... even between short-lived and long-lived ones. From what I've heard evolution seems to like recycling most of the stuff that works with minor tweaks, and most of the changes that bestow the vast difference in traits is do to tweaks in the regulation/lvls of expression/where and when it's expressed/etc of already present stuff, many a times reusing or doing minor changes to the proteins that do the actual brunt work.

We've seen that even minor changes to single genes can substantially increase lifespan in some species, and that many a times combinations of such can work synergistically and offer further increases in lifespan, along with healthspan(including the available sexually active-reproductive timespan). If such mutations are obviously arising all the time, and same with those that protect against cancer most likely(given their similar simplicity), why have they not spread throughout the population as easily as all the other stuff that I've mentioned, and has already spread? Why? My guess is selective pressure. Pressure that opposes longevity in order to provide genetic diversity(variability, and increased success of progeny of those not fittest under current environment but possibly so after change took place. ) that create a suitable environment for natural selection. Even amongst us humans there exists simple mutations that may increase the odds of reaching maximum lifespan given the lvls of maintainance/repair used by this species, as seen by centenarians and their families(IIRC, some of these traits allow greater buffers against the influence of things like diet on cholesterol profiles, and the use of larger healthier molecules to do such work, etc).

The rate and effectiveness of natural selection is itself influenceable by its very actions. Thus the core of what bestows the ability to adapt to a group is itself malleable to an extent, and can be compromised by changes in the actual composition of a group, particularly with regards to diversity.

Though the sort of programming, I believe, most likely works the way we've seen by limitting the maintainance/repair of the organism(other detrimental effects on the individual may be similar, by simply keeping beneficial mutations from spreading throughout the population, the detrimental effect is basically selected.). Thus the solution, I'd say is mostly the same as if it were not programmed at all(at least for longer lived species). It may be, as said, that repair/maintainance are built only as good as needed, and on top of that the layer of more direct programming is laid(that is two ways of shortening lifespans are to directly force it to be so despite the possibility of greater lifespan with the provided maintainance/repair/support OR to simply not engineer the necessary maintainance/repair/support for greater longevity.). Take the layer of programming off, and you'd get the sort of increases we see with cr, simple mutants experiments, and the like. On simpler organisms the most basic necessary self-repair/maintainance that's appropriate(uses as much energy as would be desirable on a per individual resource cost, without compromising variability/diversity. Being ageless would necessitate more resources per individual limitting the numbers of individuals sustainable in a particular environment/niche below the numbers necessary to maintain appropriate diversity-so as to be able to compete with other species and adapt to changes- within that particular environment/niche.) may provide substantially more lifespan than optimal(thus even exponential 2-3+x increases are seen as we take the programming layer off, by modding a few genes.), in longer lived animals the direct prog. layer's most likely closer to the actual optimal maintainance/repair that's been attained(probably required additional gradual and specific tweaking to reach that level, as opposed to the maintaince necessary to simply keep the most basic of functions/maintainance of genetic material that are obligatorily needed to be viable.) and thus smaller increases are seen.


Put another way, organisms with substantial longevity would not require as much direct aging programming as lower organisms whose lifespan may be less than that which is possible with minimum necessary maintainance for viability they are ALREADY using. This would be due to the fact that it took lots of pressure to gain that apt lvl of maintainance/repair and the organism would require substantially more of such changes as to experience exponentially significant lifespan increases(this would probably increase per individual cost past viability/sustainability in a natural-non-artificial environment for species with other already energetically expensive traits, the pressure against the accumulation of such gradual changes in maintainance/repair.), longer lived species who've been tweaked to reach such would require the spread of more gradual changes to continue increasing lifespan through the generations, provide pressure against this and you will keep such from spreading, there will be a point of balance(between accumulation of small changes that lead to greater longevity and those the sustainable number of such accumulations that can be tolerated by the group... that is without compromising variability/diversity.).

PS

Stearing a bit of this topic...

What I've been thinking, and it seems many others, requires orders of magnitude increases in the ability of many a tool, and similar increases in our knowledge at the molecular lvl. A machine that is capable of delivering and changing vast amounts of genetic material precisely within multicellular organisms. Capable of targetting all the cells within any location/organ and delivering/modding the entire code within each one, in situ. That which will ring the bell signalling the end of the age of men for the last time... by rendering the weapons of the atom useless against man's progeny... by rendering man powerless before his descendants, before posthumanity...

Such a thing given the rates of progress seems to be possible within this century. Using less general purpose and more limited delivery mechanisms specifically designed to target a particular type of cell, may hasten some aspects of this by decades.

Yet for many a tissue and for many a cell, it would seem advanced genetic engineering combined with tissue-engineering and stem cell/regenerative therapies will give us most of what'be viable with this ability(which could be available, as many've said within a few decades). Albeit not innately, and dependent on vast external support.

Given that , mortality is said to not increase after a certain point/age(as mentioned in the linked article), and that we're seeing increases in the number of centenarians/old in general. We're likely to see the maximum lifespan exceeded many a times within this century(it's only a matter of odds if the probability of death is constant after a certain point/age... more individuals, means more tries and better odds of passing such.), provided medicine/biotech/nanotech keeps exponentially increasing, we'll have a large number of individuals benefitting from diverse and combined therapies to treat, even if indirectly, aging itself. We're most likely to see as records break, and better studies of what's going on at ever greater ages, and what can go wrong at such ages even when provided extensive genetically-engineered-organ/tissue regenerative therapies, such will provide ample material to work with.

As for the former mentioned desired machinery, it could be used to target and modify cells that cannot be replaced(though the decay of cells that may need such, such as those in the brain, may be slow enough provided the rest of the body's kept ageless and providing nutrients/support optimally or beyond what's being done at present by other means, that the natural gradual replacement of such by regenerative therapies will not impair continuity of being/mind.), and it could also wipe clean and provide new virtually error free genetic material to every cell in the entire body... thus doing away with cancer and any deviation or decay in performance of original functions indefinitely(only a small number of copies of the code would have to be maintained with uber preservation-error correction/self-repair-either on the present form of molecular substrate or other form of molecular memory/error correction storage/etc-, and later distributed to the whole body at certain time intervals.-all which could be accomplished from within the body itself). Such a thing could also be used to finally provide an organism with the innate ability to modify and update its molecular memory, and supporting molecular machinery... a path that would seemingly lead towards independence of the mind from a physical substrate.

Posted by: Apocalypse at July 15, 2005 11:53 AM
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