Evolution as a Cause of Aging

[These non CIRA posts did not follow the guidelines setup for the Aging Theories thread but as they are good examples of the questions involving evolution and aging they merit their own. -kevin]
There certainly is evolutionary pressure to age and die. It's simple. If life didn't age and die it wouldn't adapt. Take red wood trees. They live thousands of years. Trees like them used to be very common. Now there are only a few stands of them.

The longer an individual lifeform lives, the slower it's species evolves. The slower it can adapt to an ever changing environment.

Secondly, people could and did live into their 70s in the stone age. Huge infant mortality rates pushed down life expectancy into the 30s.

There is no evolutionary *pressure* to age and die.. we age and die because we are increasingly ignored by life as we get older. Aging and death are not necessary for evolution. Certainly there are examples where overpopulation can cause disease and starvation, but this is not a very good argument for the appearance of aging and death as a control as very few organisms lived long enough for their genes to make any difference, for or against aging. The birthrate is a far more effective tool for evolution and the ability to pass on genetic information effectively for an organism's particular environmental niche is the only requirement.

In the broader sense what is essential to evolution is change..

Whether an organism changes to suit the environment or changes the environment to suit itself is more the process. People tend to think of evolution as something which happens to an organism rather than something that results from its behaviors although in reality the two are inextricable. Evolution is ultimately a feedback mechanism and is becoming more so. Up until the advent of the human species however, feedback to the environment has large largely been limited to reduction in resources and accumulation of waste. We are now capable of much more manipulation of our environment, replenishing and distributing resources while removing waste while making structural changes conducive to survival.

As we gain new ways to manipulate the container of our identity to fit the increasingly flexible reality offered us by insights into physics.. evolution will certainly take on a different meaning. Successful patterns of being will involve the propagation of information and selection will involve the birth and death, or rather decline, of the ideas of our minds rather than simply the information stored in our DNA.

Some thoughts that may be of relevance that I wanted to share with those participating in this topic:

The one aspect of biological science that never ceases to amaze me is the perfection and purposefulness with which biological systems work. Everything has a reason and a defined function. Evolution seems to be the driver and refiner of purpose and function in the context of environmental cues.

(before getting barraged with comments about appendices and little toes, consider that the process of evolution is generally slow)

So what is the evolutionary reason for aging?

This was a question that troubled me for a considerable period. Why is it, that of all the astounding physiological diversity that one encounters across multicellular organisms (MOs), one does not encounter the trait of immortality? It seems that the process of evolution can adapt MOs to most environmental conditions encountered on our planet, yet the ability to have an extended or unlimited life-span has eluded the adaptive mechanism.

Does that mean that life is incompatible with immortality?

Not when one considers some single celled organisms that appear to be immortal by merit of their ongoing division. For example, the HeLa cell line, conceptually a single celled organism derived from the malignant cervix of an African-American woman over 50 years ago, continues to divide today in various laboratories and looks to keep on doing so in perpetuity.

So I pondered: is evolution incompatible with immortality?

Interestingly, over the decades, the various HeLa cell lines have acquired different characteristics as each lab exposed them to varied conditions and have evolved into different strains. But not enough studies have been done to determine if unfavorable mutations rendered some of the cells mortal. And if the occasional cell died, how would the investigator know unless they were actually looking for it? Here was something to be considered further.

(Incidentally, for those interested in looking at aging versus cancer, look towards some of the work being done by Judith Campisi and her lab. She provides a satisfying interpretation about the balance between cancer cell immortalisation and the the organisms' defense against tumorigenicity and malignancy.)

Can immortality only be achieved by cancerous cells in MOs?

Not if one considers that the mammalian germ line is in fact an immortal cell line that has not lost control in the way a cancer cell does.

Is it that cellular conditions in MOs are simply too complex and tightly regulated to allow immortality to take place?

Perhaps. Yet if we consider the germ line once more, we see a subset of cells that has evolved to be immortal. The rest have evolved to be mortal.

What is the cause of cell mortality? Now this is a grand topic that has many levels of consideration. Gerontology investigators such as Aubrey de Grey has some very respectable views on the subject. Personally, I believe the cause of aging to be evolution itself. Let me explain:

Evolution is effected by providing a cell with a margin for mutation. This margin gives the cell a tiny amount of freedom for error that in the right circumstances can provide an advantageous mutation. As soon as that advantage is manifest, proliferation enables the successful mutant (or evolvant) to drown out other strains (or species). How is this margin of mutation provided? By enzymes that are in control of DNA errors (there are numerous DNA repair enzymes known with extensive studies on aging implications). If you never have any errors in duplication you have no changes in DNA sequence. Similarly if you have sufficient DNA repair enzyme no changes in DNA can occur due to damage (by mutagens, viruses, or even retrotransposons).

The moment you stop any DNA from being changed you have effectively stopped the cell from mutating and thus evolving. The DNA can still be regulated by many different processes and in turn regulate gene expression but it cannot itself change in sequence. The cell is then protected from influences that can affect its ability to function due to DNA mutations, which can in turn alter the regulation, expression and functioning of enzymes. With mutagenic protection rendered, there is very little else that can go wrong aside from the cell operating outside is environmental parameters.

With mutation arrested, evolution is arrested. The consequence of such a DNA protecting system would also result in arrest of recombination. Unfortunately, during recombination, genes do not become reshuffled in neat parcels and there is the prospect of DNA integration that leads to mutation and thus evolution each time a recombination event takes place. Thus sexual reproduction without recombination would no longer be possible due to the threat of DNA damage. Chromosomes could still be exchanged between parents but that would dramatically limit the inheritance diversity options that could take place.

The same DNA protection paradigm would also prevent the diversity mechanisms associated with the development of the adaptive immune system. However, it is possible to have a cellular subset that has some recombination function if one is willing to trade-off the possibility of cancer development. And thus one arrives back at the well worn path of the trade-offs between life-span and survival, or antagonistic pleiotropy.

If we consider the functional specificity of biological systems we can see that this design did not come about by accident. It is the only way life can survive in a changing environment. A balance between the possibility of evolution with each new generation and the increasing possibility of disfunction within the generational lifetime. Theoratically, in order for an organism to be immortal it must cease to be able to evolve and sexually produce. Unless the organism was able to clone itself (i.e. via parthenogenesis) its population would remain static. Such a state would render an organism very quickly extinct unless it was able to exist in an environment that was constant or was able to change its genetic make-up non-randomly.


The cause of aging is inseparably intertwined with the molecular mechanisms of evolution.

You make some good points prometheus1..

Aging *is* interwined with the molecular mechanisms of evolution, but is not indispensable to those mechanisms. That a bat can live five times as long as a mouse, indicates that mutations have given rise to very different lifespans in these genetically very similar species. This is thought to be because a high mortality rate amongs ground dwelling rodents has not allowed for the selection of longer lived individuals which is not the case with the bat who has the enviable ability to fly to escape from predators.

This is obviously a case where longevity and aging are interwined with evolution, as there could be no selection for genes extending lifespan otherwise. It also shows that longer lifespans get selected for when extrinsic causes of mortality are reduced allowing the organism the chance to further reproduce.

Reproduction is the key. As you point out, of primary importance is the passing on of the DNA via transmission through the germ line. The body, and perhaps even intelligence, are capabilities which have evolved with the sole purpose of maximizing the opportunity for propagation in a particular environmental niche. The propagation of the information in the DNA of the germ line amidst competition for finite resources for that propagation is the underlying "motive" of life IMO.

The removal of organisms by aging and death is not necessary for reproduction or evolution and is in fact is a negative influence which is selected against as animals are able to reproduce at older and older ages. It is only when an organism has the luxury of escaping extrinsic factors of mortality such as starvation or being eaten that genes encouraging longevity begin to have effect as they have offspring at later ages than their ecological niche might have previously allowed.

Although your point that aging is inseparably interwined with evolution is well taken it is clear from the above that aging is not a prerequisite of evolution, rather reproduction primary.

Reproduction is linked with evolution because they share a common mechanism: random changes in DNA sequence that are brought about by recombination during the fusion of germ cells. If the DNA were to remain constant there would be no opportunity for mutation and therefore no possibility for evolution. Strangely, this same mutation potential exists in all somatic cells and is a major cause of cell pathology when DNA is mutated and as a consequence the enzymes it encodes for begin to lose function.

Naturally this is not the only reason somatic cells become senescent or apoptotic. Telomerase, which is only present in germ line or stem cells, is also absent in somatic cells. Big problem there, because even if the cell maintains perfect DNA integrity with no chance of enzyme malfunction the cell will eventually reach its Hayflick limit. Then the only way for renewal is via the local stem cell niche. Ironically, as soon as the stem cell's role is defined it signals for the down-regulation of telomerase. But these niches too become deficient as time goes on and the organism generally loses its capacity for regeneration. Here is another question: why prevent a specialized cell from being able to divide indefinately? Likely because it may be more vulnerable to carcinogenesis.

Strangely, those cells that require the most precision in function, i.e. cells been allocated their final physiological role, also have DNA repair enzyme function in "mutation/evolution mode". Whilst there is a benefit in switching telomerase off (due to the possibility of cancer), why not up-regulate DNA repair enzymes and ensure that the cell will maximize its functional life-span despite its Hayflick limited division cycle. This implies that there has been no evolutionary advantage in switching this crippling effect off in non-germiline cells which are the sole beneficiaries of this influence. The reason for this is simple: if you make too much DNA correcting enzymes you will stop mutation and therefore stop evolution.

So we come back to evolution. In order to to benefit from evolution the mechanism of DNA repair must be slightly dysfunctional such that errors can be introduced. These errors lead to aging. Ergo aging is caused by the mechanisms of evolution.

One positive note out of all this: when one considers the way this system works it is brilliantly balanced. It is a perfect mechanism for sustaining an ongoing system of life that has the potential to adapt in order to survive. The next level of evolution is when the organism becomes aware of this mechanism, is able to develop technology t arrest the random aspect of it, and is able to regulate its own evolutionary destiny. Which is where the human race, barring any catastrophe, should be within 50 - 100 years.

The reason for this is simple: if you make too much DNA correcting enzymes you will stop mutation and therefore stop evolution.

The reason we have not evolved better repair mechanisms is not because it would stop evolution. The reason is because the genes that would encourage better DNA repair are unnecessary. In order for such mechanisms to develop we would need to reproduce at older ages in order for natural selection to have effect. Our systems are all geared towards optimal reproduction starting at puberty and ending somewhere in the mid-20's after which our genetic code is quite happy to let us rot as we were unlikely to have survived long enough in the wild to reproduce at older ages. It is one of the cornerstones of aging theory and has been proven many times over that the force of natural selection, evolutionary pressure, declines as organisms age and as a result, genes which promote longevity, ie. better repair mechanisms, never have the chance to develop. This is, I believe, why better mechanisms have not been developed, not because evolution would stop.

I do not wish to belabor on this point too long, but I am concerned that importance of the link between evolution and aging is being swept aside in the static of other ideas.

Firstly, I believe that we are in agreement that DNA repair mechanisms are finite. This is an important distinction with enormous ramifications.

Further we must confirm that we are talking about the same thing when we describe mutation (the mechanism of evolution) and damage. For the sake of illustration assume any linear sequence of latin letters corresponds to a DNA sequence and that the genes encode words. The following examples demonstrate the difference between mutation and damage:

a) Mutation:
source sequence = LOVE
received sequence = LIVE (different meaning > different function)

b) Damage:
source sequence = LOVE
received sequence = LFVE (nonsense > no function)

The consequences of the type of damage will determine the cellular response to the DNA change if it goes unrepaired. These responses include transcription termination, replication impairment, etc. that ultimately result in decreased cell survival. The consequences of mutation are a change in enzyme function - usually reduced turnover. The rate at which these type events occur have been estimated at about 100,000 per cell per day. These are the *known* events. We can safely assume there also unknown events capable of driving these number higher. Of paramount consequence is that most error correcting enzymes find it more difficult to repair a mutation based change rather than a damage based change. This means that mutations will have a higher rate of passing through error correction systems than damage. As a result, the cell must provide for additional security mechanisms for regulating runaway mutations. These include numerous checkpoints that attempt to ensure cell integrity. One of these seems to be telomerase inhibition.

Now you would have to agree that if repair mechanisms functioned at an increased rate, the rate of mutation and damage would subsequently be reduced. Increased repair results in decreasing evolution and the slower the rate of evolution the greater the risk of non-adaptability should environmental conditions prevail that a change is necessary to ensure survival.

Your argument is that better repair mechanisms never have a chance to develop. In fact, in some bacterial and drosophila DNA repair mechanisms have been shown to adapt in UV radiation and other mutagen exposure conditions by increasing repair functionality. Effectively, they have upped the rate of DNA repair to compensate for increased rate of mutation, thereby *slowing* their internal rate of mutation. This demonstrates that the system of DNA repair is adaptable and seeks to regulate itself homeostatically in order to maintain a level of mutability. Thus the rate of repair is adaptable and has evolved to be at a particular rate. Conversely, DNA repair mutants such as those afflicted with Werner's Syndrome have an abnormally low level of DNA repair function. Studies on centegenerians have shown that one of their cell function differences from those of average life-span is that they have increased levels of DNA repair enzymes. This demonstrates that changes in repair systems are able to evolve in life ranging from bacteria to humans, but only within a defined range of activity that seems to operate homeostatically.

Now I know that I will be leaving the realms of the debate, but I would like you (all participants of this forum) to consider this: Assuming that such a homeostatic mechanism of mutability or rate of evolution exists in the cell, what type of system would it operate by?

As examples of the systems I am talking about:
a) somatic cell division limit - governed by systematic telomere end disintegration with each cell division (due to down-regulation of telomerase)
b) cell repair - governed by growth transcription factors sequestered in extracellular matrix and released when matrix is damaged

Better still, imagine you are the architect of such a system, how would you design it to be sensitive to rate of mutation so that the rate could be kept constant?

Take note that only a single copy of DNA from the germline is allowed to pass down the inheritance funnel, thus the evolutionary path can only occur via the germline and via recombination with the sex partners DNA. Any changes in DNA independent of the recombination can only occur in the hereditarily insulated germline*.

* There is the heretical possibility (aka Lamarkian evolution) that somehow DNA exchange occurs between somatic and germline cells during the course of life thus tying in the entire system of somatic and germline cell DNA repair. Then it would make sense that you would keep both rates of mutation even between these two types of cells. Very speculative of course, but I do recall a study that demonstrated something like this in terms of immune system inheritance.

Your argument is that better repair mechanisms never have a chance to develop. In fact, in some bacterial and drosophila DNA repair mechanisms have been shown to adapt in UV radiation and other mutagen exposure conditions by increasing repair functionality.

The key word is adapt. You are talking about directed evolution under changing conditions selecting for a trait in reproducing organisms. If our species were subjected to increasing levels of radiation which damaged our germline before we were able to reproduce, only those that had better DNA repair would be able to pass on their genes and we would definitely see better DNA repair. I seem to recall that DNA repair in the germline is different that that of somatic tissues as well. That evolution occurs does not support your assertion that aging is caused by evolution.. at least I think that is what you're saying. Your example does not speak to the point that I was making that genes which promote longevity do not get selected for because older animals (post-reproductive) rarely survive in the wild to pass on their genes. Our entire genome is geared to pushing us off at birth and reproduction, after which we fall victim to the forces of ENTROPY, much like gravity attracts the ball thrown into the air back to earth. Aging is a consequence of decay.. not some "active" program.... not evolution.

Many many research scientists and people smarter than I subscribe to this view and indeed there is a lot of evidence pointing to its validity.

Entropy by definition is the amount of disorder in a system.

You cannot compare entropy to aging because aging is not based on entropy. Biological systems have the capacity to renew themselves, i.e. to continue to drive their biochemical reactions *perpetually* provided the appropriate substrates and enzymes are available in suitable conditions. Cellular mechanisms are extremely precise. When a cell dies it does so either by apoptosis or trauma. Taking trauma out of the picture, cell death is a very controlled mechanism and not subject to disordered states.

I think you are saying that rather than aging is the result of accumulated errors. Which is precisely what I am saying - due to insufficient DNA repair. There is plenty of evidence to support that DNA damage is cause of death in animals. The only mechanisms that can compensate for that damage are cellular proliferation, cellular redundancy, apoptosis of severely damaged cells (where the cost of repair is greater than that of regeneration) and DNA repair.

Aging as a cause of Evolution Hypothesis:

FACT: Evolution occurs as a result of change in DNA.

FACT: DNA can only change if DNA repair enzymes have not repaired the change OR by recombination

FACT: Proportion of non-recombination DNA change is inversely proportional to concentration of DNA repair enzymes

FACT: DNA repair enzymes decrease with age

FACT: DNA repair enzyme expression is adaptable

It does not take a wild leap of the imagination to see that Evolution needs a degree of insufficiency in DNA repair in order to occur. The mechanism of aging is linked to evolution by the mechanism of DNA repair. I am of the opinion that when a cell is instructed to enter apoptosis mode, it is programmed actively to enter a suicide mode. The sequence of events, the genes, transcription factors, enzymes, etc. that activated do take a highly ordered and deliberate mode. Now if this can happen on a cellular basis, why is it so difficult to accept that it happens on a tissue, organ and organism basis? The consequence of a the breakdown of a vital organic process that leads to death does always follow the same pathway as any medical textbook will state. What you call decay, is a very ordered process, which is why pathologists can determine cause and reason of death by analyzing cells and tissues post-mortem.

The reason why genes that promote longevity do not get selected is that they will interfere with the rate of evolution - and that could be catastrophic to a population. One of those genes that could extend life-span - say a more efficient transcription factor sitting next to a gene coding for an DNA repair enzyme would always be selected against. Imagine the scenario: a population of humans capable of living for 300 years, the rate of genetic divergence would drop dramatically. A competing population with an average life-span of only 30 years would be able to adapt much faster.

Nature loves rolling the dice. And thats my point. she keeps on rolling them, and rolling them, and rolling them... She loves to play. Longevity slows things down for her.

The reason why genes that promote longevity do not get selected is that they will interfere with the rate of evolution

This is pretty weak...
Just so you don't think I haven't thought about what you propose before.. this was one of the first articles I posted on the forums..

Post: http://www.imminst.o...1153

Link: http://www.azinet.co..._Evolution.html

which is a very interesting article that speaks about the need for genetic diversity in populations as dictating the fitness of a population and its ability to adjust to changing environments. As oscrazor says reproductive fitness is what is being referred to in reality, not programmed aging.. something I've come to recognize somewhat myself.

I've come to realize that evolution is the result of a natural tendency to disorder and needs no encouragement by considering it an 'active' process.. it happens as a result of thermodynamics. The deterioration make look as if it is planned, but this is just the same thing we see when any complex object is subject the elements.. for example.. the first thing to go on a house is usually the roof and exterior. One may look at the process of dilapidation and assume that there was some script it was following but in reality it is just because those components are the most exposed.

Attempting to keep the ship together long enough to pop off a few offspring is really what evolution is concerned with.. Evolution is all about life.. and nothing about death..

You are looking at aging as a directed process and I do not.. I daresay that the bulk of evidence is on my side although of course there is no absolute proof for either.

------------------------
glad you reposted back to the thread.. I wasn't sure you understood the nature of the format required..

It is only when one dissects the various molecular mechanisms of aging and finds that the main protagonist to be DNA damage that the convergence between DNA repair and rate of mutation become apparent.

Indeed as per your cited online article and as was widely published 2 years ago, 51 scientists including the venerable Hayflick stated that aging cannot be treated by any currently marketed intervention and alluded that aging is not an evolved characteristic. Whilst this article's purpose was more in line with debunking a lot of snake oil anti-aging therapies it did make the point that aging is only indirectly regulated by evolution i.e. as a result of the cumulative effects of unrelated genes. Basically the article said that there are no genes that directly govern the aging process. I am conversant with this article and its premise.

However, what I am saying is that the very mechanism of evolution, being DNA change, is allowed to occur only by the reduction of DNA correcting mechanisms. This very same mechanism causes aging. Evolution cannot take place without a relaxation in the DNA correcting systems. It is at the heart of aging as it is to evolution. Is it so hard to understand?

Is it so hard to understand?

Do you mean understand, or agree?

I understand quite well what you are saying, the concept is not a difficult one. It's just wrong.. There is nothing to 'relax' according to the vast majority of experts in the field of aging... of which I'm not one so I defer to the huge number of papers supporting it.

Tom Kirkwood introduced this Disposable Soma Theory, in the 1970's so it is hardly new and you are likely well aware of it. In it he proposes, and thus far his assertions have held up, growth and reproduction take precedence over maintenance in high energy environments. It is in an organisms best interests in the wild to "get while the gettins' good" in order that it can reproduce so it is quite natural to see how systems evolved to allow for reproduction at the expense of the body in a world unsure of survival or resources. Maintenance is not 'relaxed' because of some requirement for evolution, it is abandoned because of tradeoffs in resource allocation towards reproduction which is very different that what you are proposing. This idea is being further borne out by studies currently underway in the Sir2 pathway which seems to be a conserved switching mechanism directing energy towards either scenario depending on available energy.

More interesting to me than the role of unrepaired DNA point mutations in producing new function, which I consider a largely entropic and random process requiring resistance rather than promotion, is the more active mechanism of the introduction of genetic variability through recombination during reproduction.

Now THAT is an active process. No need to invent anything there.

If the rate of evolution in an organism can be classified as an inherited trait, does that not mean that as an inherited trait it is also subject to the "laws" of evolution? And if this trait also affects aging would it not be correct to say that evolution influences aging?

Aging is an epiphenomenon of evolutionary processes which select for higher fecundity at a young age, but is in no way directly selected for by evolutionary pressure. So yes, evolution influences senescence processes, but evolution definitely doesn't use it as a selection mechanism.

More interesting to me than the role of unrepaired DNA point mutations in producing new function, which I consider a largely entropic and random process requiring resistance rather than promotion, is the more active mechanism of the introduction of genetic variability through recombination during reproduction.

Mutation is the ultimate source of all variation, but in the short term, a large amount of variation within a population is due to recombination amongst pre-existing alleles. The two processes are not independent.

If we consider the mechanism of mammalian recombination we see that it is intimately associated with DNA repair (1). Recent studies showed that there is an direct relationship between recombination and DNA repair in yeast (2), drosophila (3) and in mice (4).

We know that mutations are the medium by which evolution occurs. UV light and other mutagens are often used in the lab in order to accelerate the rate of mutation. There is also another way of increasing the rate of mutations and that is by creating knockout mutants that are homozygous for DNA repair genes. The result is the same as an increase in environmental mutagens. By dropping the level of DNA repair we observe an increased rate of mutation and an increased rate of evolution. Thus the rate of mutation is a function of the amount of mutagen versus the amount of DNA repair.

Now supposing the rate of DNA repair increases as compared to the that of the rate of mutation. We would observe a drop in the rate of mutation and a subsequent drop in the rate of evolution. If DNA repair were to be cranked all the way up and there was hardly any mutation occurring then we would observe a dramatic drop in the rate of evolution. This could be catastrophic to a population if there was a change in environment that required adaptation by the population. Thus the capability to mutate is necessary for evolution and for survival and is a characteristic that is selected for.

Aging is an epiphenomenon of evolutionary processes which select for higher fecundity at a young age, but is in no way directly selected for by evolutionary pressure. So yes, evolution influences senescence processes, but evolution definitely doesn't use it as a selection mechanism.

Consequently a high level of DNA repair is selected against. With DNA repair being selected against, aging, by merit of cumulative DNA damage is selected for. And thus we have the sad state of affairs that evolution selects for aging via pressure to keep DNA repair at a rate sufficient to enable mutations and drive evolution.


(1) Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis.
Exp Cell Res. 2004 May 15;296(1):71-9
(2) DNA repair defects channel interstrand DNA crosslinks into alternate recombinational and error-prone repair pathways.
J Biol Chem. 2004 Jun 22
(3) Mutational analysis of the Drosophila DNA repair and recombination gene mei-9.
Genetics. 2004 May;167(1):263-73
(4) Collaboration of homologous recombination and nonhomologous end-joining factors for the survival and integrity of mice and cells.
Genes Dev. 2004 Jun 1;18(11):1293-304.

You are looking at aging as a directed process and I do not.. I daresay that the bulk of evidence is on my side although of course there is no absolute proof for either. -kevin

I'm not sure if the old version of that article covers it, but the new one does. The aging process begins taking place from a very early age, near sexual maturity, some aspects I've heard start slightly before sexual maturity. This one would think is compromising fitness, and however small if so it should be selected against, unless it offered more than it took, that is unless it was a worthy trade, unless it instead increased fitness. That is the deterioration begins at a very early age, as I've said I've heard some areas begin deteriorating prior to sexual maturity, that should not be possible... unless it made the organism fitter.

The new theory posted at betterhumans, is similar to what I'm suggesting, though I do not dismiss the possibility of other mechanisms being involved.

New theory

It's likely that hormonal changes do account for the diverging lifespans in an organism to some degree, the C-elegans got a six fold boost from messing with it. That seems to indicate that something else is also involved, an alternate regulation mechanism, at what level(intra-cellular, tissue, organ, etc)? Maybe it's just that this is the whole program but the C-elegans being short-lived has not evolved the maintainance/repair mechanism needed for negligible senescence, that is those of longer lived organisms or maybe it's not the whole thing.

Analysis of the genome of a negligible senescent species, and close, same genus, short-lived(they're not as short as C-elegans, some about 12yrs) species, should yield the answer. By knowing how long ago they diverged, and how many mutations are involved we would have a clue as to whether it's easy or hard to achieve negligible senescence. Further analysis would probably yield the answers to what must be done, were to direct our efforts.

Hayflick stated that aging cannot be treated by any currently marketed intervention and alluded that aging is not an evolved characteristic. - prometheus

As others have said, it's amazing Hayflick dared to use the word impossibility, IIRC, a word seldom used in scientific circles.

Maintenance is not 'relaxed' because of some requirement for evolution, it is abandoned because of tradeoffs in resource allocation towards reproduction which is very different that what you are proposing.-Kevin

I've heard of experiments that disagree with this, maybe I posted some in the aging thread, not sure though. Also, Cynthia Kenyon's said she thinks that by simply altering the hormonal mechanisms, 6 fold lifespan increase together with reproduction capacity should be possible, in C-elegans.

edit:

Just recalled... here's an example by slightly altering the C-elegans, a dauer like abnormal lifespan( not the six fold one, smaller, IIRC) was achieved without compromising fertility, mobility, strength, etc.


Here's an interesting quote:

Our laboratory studies the regulation of aging. Not very long ago, most people thought that aging was something that just happened. We just wear out, like cars. Not true! Several years ago, we discovered that mutations in the gene daf-2, which encodes an insulin/IGF-1-like receptor, double the lifespan of the nematode C. elegans. Since then, insulin/IGF-1 endocrine systems have been shown to regulate the longevity of flies and mice as well. We have found that this system is regulated by sensory neurons in C. elegans, and that signals from the reproductive system also regulate aging. Amazingly, if we perturb insulin/IGF-1 signaling and reproductive cells in the same animal, we end up with animals that live SIX times as normal! WhatÕs more, they stay vibrant and healthy until the very end. We have also discovered that a different regulatory system involving mitochondria functions during development to set the rates of behavior and aging. We are now trying to understand how the insulin/IGF-1, reproductive and mitochondrial pathways, as well as another perturbation, caloric restriction, influence lifespan at the molecular level.

pibs faculty kenyon

Edited by apocalypse, 25 August 2004 - 10:05 AM.

Continuing the ideas from my previous post.

"When we asked people why they thought they lived so long, we got two answers," Barzilai said. "The first was that they had a mother who lived till 102 or a grandfather who lived till 108."

"The second answer was that they had 'something' protecting them. These were not people who exercised, they weren't vegetarians, some smoked heavily, some were very obese—but they could do anything and get away with it."

Apparently longevity and good health don't always go together. "Some [centenarians] have delayed age-related diseases, some have escaped [them] but most have survived [them]," Jeune said.

Jeune's study has followed 300 people who reached their 100th birthday in 1995. Two of the remaining three died last week. "They were at opposite extremes," Jeune said. "The man had the fewest number of diseases in the entire study group; the woman, the most—she had 20 hospitalizations and six major operations."

national geo aging

Isn't it amazing someone might be a heavy smoker, and still live longer than a healthy non-smoker.... though, that's supposed to be delivering massive doses of carcinogens(If I'm not mistaken), the centenarian kin is able to overcome it.

Another interesting link following the same thread of thought.

Thanks for appearing on "Never Say Die." I enjoyed learning about your work, and I'd like some of that stuff right away, please. Alan Alda asked what possible reason an organism would have to cause its own demise, and you said, essentially, nobody knows. I always thought that it would be beneficial for the old generation to get out of the way for the new one. Otherwise, the old guys would be around competing with the new guys, who hopefully have the better genes. Is this a completely wacko idea? (Question from Bob)

A I like your idea. Here is my favorite idea: In the presence of food and low population density, worms reproduce rapidly, producing 300 progeny in the first three days of adulthood. That's an amazing rate of compounding. (Imagine your 401k compounding at a rate of 300% every three days. Soon you would own everything (very soon).) For the worm, this is a strategy that converts whatever the worms are eating into more worms very rapidly. Now, I didn't say this on the TV show, but we know that the long-lived mutants are resistant to damage caused by oxygen (free radicals, which produce oxidative damage) and other environmental stresses. We also know that at least some genes, like a gene encoding the protein superoxide dismutatase (which prevents free radical damage) are expressed at very high levels in these long-lived worms. It seems to me that it would be energetically more expensive to produce such a "superworm". Therefore, a population that did this (used some of its food to make the worms more resilient than then need to be just to produce their 300 progeny) might lose out to one a population that converted every drop of food into more worms. -kenyon

Q & A


EDIT:

Now, that I think about it, this is another reason for why it could've evolved. It's similar to the "reproduction and maintainance balance" difference is, the organism does not necessarily need to make a trade-off to keep reproduction abilities. That is, the organism could compromise its maintainance/repair not to be able to keep basic reproductive abilities but to allow for even more offspring[that it could have also had while keeping the added lifespan, but that higher resource needs would prohibit survival of many of such offspring even if produced] by freeing resources, for more members, that is to leave these for the next-gen, for the construction/maintainance of more members. If a whole population used them in maintainance/repair, there'd be less total members cause they're all maintaining this trait, which costs resources that could go into additional members instead.

I had thought that in times of scarcity this probably could be downregulated to allow the organisms to expand and out-compete others, since they were better maintained prior to such period. But restoring this up, during the good times, would also be costly, they would use resources that could go into new member construction and maintainance, and thus other species could out-compete them.

An analogy for this is a company in need of some cars. It has to decide whether to have a couple of bmws, or a lot of cheap cars. If it gets the former the costs will prohibit it from increasing it's numbers as fast as occurs in the latter or maintaining such numbers once achieved, due to the the maintainance/repair/purchase costs while using the same number of resources.

Edited by apocalypse, 25 August 2004 - 12:52 PM.

Does anyone contributing to this thread object to my merging it with the parallel thread DNA, In My Opinion, Is The Cause Of Aging ?
http://www.imminst.o...4&t=4126&hl=&s=