A Theory For Why We Age!

[foodchain]

Did you even read anything that was said before? Telomers are about your cells aging, not you. Because your cells age each time they reproduce, a mutant cell that reproduces uncontrollably will age and die, preventing cancer. A cancer only happens when the cell becomes immortal and reproduces uncontrollably. If all your cells were immortal, every tumor would be a cancer. You might get cancer when you are about 5 years old instead of 75, way before you get to reproductive age. Cell aging just means you need two mutations instead of one to get cancer.

 

Right but the same reality of a telomeres in context of multicellular beings operating in concert can also be found in developmental processes. Such as how much of a certain cell type or for how long. Which goes into molecular clocks as being described here. The issue is that the role of telomeres is being brought up as an ends to cancer in which study on the subject can find telomere behavior related to various negative health conditions that go outside of the scope of being cancer related or even combating cancer. So what is the value again? Also would it simply be just as equal to say that the evolution of various behaviors such as cell division, molecular clocks and the control of morphogenesis be enough to explain while such aspects of an organism persist, and lastly I still cant see any physical connection and or evidence past logical deduction.

 

The only avenue in which I could agree with telomeres being related to combating cancer has more to do with mutation and or reorganization of the genome. For instance when bacteria are culture in experiments to force evolution. If life per say experiences such and tends to leave normal fixed traits behind I could see this pertaining to telomere behavior in regards to placement of such for stabilization purposes. The other issue though is evolution wont occur if the species does not reproduce, which also means the parents have to say alive and or cancer free long enough to do this. So again the only avenue I could see to test such for empirical means would to be relating phylogeny time wise to various species to telomere behavior in the face of adaptation and selective pressures.

 

Personally I just don’t see anything from a molecular/cellular viewpoint up to whole species to support this. Humans are a perfect example with a good deviation of mean lifespan, to just about any other specie really. I just don’t see telomeres behavior and or use indicative of combating cancer, but more or less just as aspect of biology that has not been made extinct from selective pressures, such as simply being able to function. I mean if you develop cancer and become sick, odds are that natural selection will be combating such a phenotype in the development of a genome or organism. Not that the body does not have various means to retain fitness such as DNA repari mechanisms to killer cells to behavior to combat short strings of RNA being introduced, just that I don’t see past logical deduction any evidence really to support the hypothesis.

[Mr Skeptic]

What I said still applies. Ageing cells can still go cancerous and form a tumour.

 

No they can't. They can become a tumor, but they cannot become a cancer unless they loose the aging aspect. Cancer cells do not age, and therefore aging cells cannot be cancer.

 

In fact, this happens far more often in aged individuals than in young individuals.

 

Don't confuse age and time. You start off as a (usually) perfect cell, and as time passes, you accumulate mutations. You don't accumulate mutations because your cells age, you accumulate them because time passes. A colony of non-aging cells will still accumulate mutations, as evidenced by any single-celled organism.

 

The only time cell aging causes mutations is when your cell runs out of telomers, but those are mutations to the ends of the DNA strand, and usually result in the cell dying.

[losfomot]

Here is a 19 minute talk that I think you should listen to. It starts a little slow, but is actually quite fascinating. The gist of it is that cancer seems to be a direct result of injury to our bodies (ie - if you smoke you are damaging your lungs and have a higher risk of lung cancer) so perhaps cancer is part of the bodies healing mechanism gone bad. My understanding of what she is saying is that cancer is the bodies way of trying to replace the damaged tissue with new tissue... but something is going wrong. Anyway, I think it relates to this discussion if not to the OP, and it really is a fascinating talk. Check it out.

[SkepticLance]

To Mr Skeptic

 

Sure, ageing cells have to be 'rejuvenated' to become cancerous. However, this applies to cancers in people of all ages. Ageing as such makes you MORE, not less prone to cancer. The probable reasons for this include accumulated genetic errors, but also a reduction in the power of the immune system, hence making it less able to fight cancers.

 

The point is that cancers are usually a consequence of ageing. They do not, even through evolution, cause ageing. Ageing probably has many causes, as previously listed in this thread.

 

Telomere shortening is part, but only part of the mechanism of ageing. A lot goes on inside a living cell as it ages. Telomere loss is only part of it.

[Mr Skeptic]

Sure, ageing cells have to be 'rejuvenated' to become cancerous. However, this applies to cancers in people of all ages. Ageing as such makes you MORE, not less prone to cancer. The probable reasons for this include accumulated genetic errors, but also a reduction in the power of the immune system, hence making it less able to fight cancers.

 

And as I said, cells that don't age don't need to be 'rejuvenated' to become cancerous. All they need is to start reproducing uncontrollably.

 

The point is that cancers are usually a consequence of ageing. They do not, even through evolution, cause ageing. Ageing probably has many causes, as previously listed in this thread.

 

No, cancers are mutant cells with that reproduce uncontrollably and don't age at the cellular level. The only thing aging on the organismal level has to do with it is that the longer you live, the more mutations you get. If you really think that cancer is due to aging, go expose yourself to some radiation or mutagens. Its mutations, not ageing, that cause cancer.

 

Obviously any uncurable and cumulative damage to an organism will be "aging" for the organism. I've been focusing on telomers and cancer because that's what people want to argue about. My point is that cell aging allows you to live much longer (because you won't be as likely to get cancer).

 

Telomere shortening is part, but only part of the mechanism of ageing. A lot goes on inside a living cell as it ages. Telomere loss is only part of it.

 

But cells don't necessarily age. Just ask your kids. If cells always aged, you'd be over a million years old. The stores wouldn't carry enough candles to put on your cake

[SkepticLance]

Mr. Skeptic said :

 

"My point is that cell aging allows you to live much longer (because you won't be as likely to get cancer)."

 

The nature of cancer is that, in certain respects, the cells 'rejuvenate'. Thus, cells being older is NOT a protection. Quite the opposite, since the older cells are far more likely to contain the errors leading to cancer. In addition, as I said before, the cancer is less likely to be controlled by the ageing immune system.

 

If cells could be kept 'young' by some genetic repair system, cancers would be much rarer. This is shown by the much lower rate of cancers in young people.

[Mr Skeptic]

The nature of cancer is that, in certain respects, the cells 'rejuvenate'. Thus, cells being older is NOT a protection. Quite the opposite, since the older cells are far more likely to contain the errors leading to cancer. In addition, as I said before, the cancer is less likely to be controlled by the ageing immune system.

 

I never said cells being older is protection. It is cells aging each time they reproduce that protects from cancer.

 

If cells could be kept 'young' by some genetic repair system, cancers would be much rarer. This is shown by the much lower rate of cancers in young people.

 

No, now you are confusing with genetic repair and youth. If cells did not mutate or repaired their mutations or died whenever they got mutated, there would not be cancer. What does that have to do with being young? Babies can get cancer too, you know. Cancer is all about mutations and has nothing to do with being older.

 

Perhaps this analogy will help:

Among young children, the number of cavities a child has is higher the larger the child's vocabulary. Does that mean that vocabulary causes cavities? No, it means that older kids have both more cavities and a larger vocabulary.

 

Likewise, older people have more cancers. Does being older cause cancer? No, being older means you have more mutations, and it is the mutations that cause the cancer.

[SkepticLance]

To Mr. Skeptic

 

When cells undergo meiosis and then recombine (in other words - sex), they begin again as a zygote which grows into a young organism. This young organism once more has the resistance to cancer that all youth has. Yet the cells come from very old cells. But this method of rejuvenation restores cancer resistance.

 

Rather than ageing to 'protect' against cancer, a much better strategy would be rejuvenation. The idea that ageing is an adaptation against cancer, even at cellular level makes no sense. To resist cancer, the vigor of youth is far more effective.

 

Anyway, there are a number of other known probable reasons for ageing that make much more sense.

[foodchain]

"Abstract

Telomerase activity is one of the most important factors that have been linked to multiple developmental processes, including cell proliferation, differentiation, aging and senescence. Dysregulation of telomerase has often been found in developmental abnormalities, such as cancer, loss of function in the hematopoietic system, and low success rate of somatic cloning. A comprehensive network of transcription factors has been shown to be involved in the genetic control of telomerase expression and activity. Epigenetic mechanisms have recently been shown to provide an additional level of regulation, and may be responsible for the diverse expression status of telomerase that is manifested in a tissue and cell-type-dependent manner. This article summarizes the recent developments in the field of telomerase research with a focus on the coregulation of the telomerase gene by both genetic and epigenetic pathways. Developmental consequences of aberrant telomerase activity will also be summarized and discussed."

 

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T39-4CY5KX2-1&_user=10&_coverDate=09%2F29%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=94956ad6b1ed53d57b5a856510bfa3e6

[Mr Skeptic]

When cells undergo meiosis and then recombine (in other words - sex), they begin again as a zygote which grows into a young organism. This young organism once more has the resistance to cancer that all youth has. Yet the cells come from very old cells. But this method of rejuvenation restores cancer resistance.

 

Rather than ageing to 'protect' against cancer, a much better strategy would be rejuvenation. The idea that ageing is an adaptation against cancer, even at cellular level makes no sense. To resist cancer, the vigor of youth is far more effective.

 

The only rejuvenation that is going on during reproduction

1) telomers are added to the cell, so it can reproduce more times without dying

2) The overly mutant cells die

 

1) is about aging, while 2) is what actually starts youth off with a clean slate.

 

If you could eliminate mutatant cells from your body, you would not need the aging mechanism to fight cancer. But you can't. Yet.

 

Anyway, there are a number of other known probable reasons for ageing that make much more sense.

 

Please list whatever causes you know for cell aging. There are various reasons a whole organism ages, as I said, any cumulative and uncurable damage can be considered aging.

 

---

 

SkepticLance, I tire of correcting you on this. Youth does not prevent cancer. Age does not cause cancer. Mutations cause cancer, and older people have more mutations (because they are cumulative). Expose a youth to mutagens, and he will rapidly develop cancer even though he is young.

 

The aging of cells (losing telomers, not old age!) prevents cancer, because cells must stop aging before they can become cancer.

 

I will stop correcting you on these matters hereafter, so you will have more free time to debunk Global Warming

[SkepticLance]

Mr Skeptic

 

You fly in the face of empirical data.

Young people have very low rates of cancer.

Old people have very high rates of cancer.

Age causes cancer. It does not protect against it.

[iNow]

Age causes cancer.

No friend, it does not. Would you be able to share with all of us some of this empirical data you reference that shows age causes cancer? Please recall in advance that correlation does not mean causation.

[Paralith]

This argument between you two is going in circles. Let's try phrasing this argument somewhat differently. The (purported) mechanism that prevents cancer causes (or at least significantly contributes to) the eventual breakdown of the human body. It's not that aging stops cancer. It's the reduction of telomeres that stops cancer. And it's the reduction of telomeres that contributes to the breakdown of the body. This breakdown of the body increases as age increases, since telomeres decrease as age increases, and this breakdown in itself is often called aging, though technically aging should simply mean an increase in the amount of time you have been alive.

 

There. Does that help?

 

Edit now that I've seen INow's post: Again, let's rephrase. Every time your cells divide aka their DNA replicates, there is a chance that a mutation that could cause cancer will occur. Thus the higher the number of times your cells have divided, the higher the chance that a mutation that causes cancer has occurred. Since the number of times your cells have divided increases as your age increases, the chances that you have contracted cancer increases as your age increases.

 

Now, I'm not going to get into the argument about whether that's correlation or causation or both, but I think you all are arguing much more about the letter of the law than about the spirit of it.

[SkepticLance]

To paralith

 

You are correct in that shortened telomeres reduce cell division - hence cancer. Where that argument breaks down is that a cancer cell undergoes a kind of cellullar regeneration, meaning all telomere bets are off! The fact is that older people suffer much more cancer than younger, meaning that telomere length as a factor is much outweighed by other factors, such as more cellular mutations, and reduced immune response. Thus age causes cancer, not preventing it.

 

To iNow

 

If I had a dollar for every time someone said 'correlation is not causation".....

 

If you see a correlation, such as the one between greater age and greater chance of cancer, there are four possibilities. Let us call greater age "factor A" and the chance of cancer " factor B".

 

1. First possibility. The correlation is faulty. In this case, that is not so. Literally thousands of studies have shown that the correlation is sound. No medical researcher doubts that age and cancer rate are correlated.

 

2. A causes B. Which seems very likely, at least as part of the story.

 

3. B causes A. This would mean that more cancer causes ageing. An interesting theory, but not consistent with observation. Ageing clearly happens even when cancers are not measurable.

 

4. Both A and B are caused by extra factor C. This would mean that some outside factor causes greater age, and also causes cancer. There may be some truth in this, if we assume that external factors causing mutations ©cause both A and B. We have to be a bit cautious on this, since the full cause of both is not always known. Call this a reasonable possibility. Personally I regard it only part of the story, since we know that older people have poorer immune systems, and are prone to such things as extremely serious pulmonary pneumonia, which is frequently fatal. Since the immune system also fights cancers, the break down would be part of the reason for the correlation, which is possibility 2.

 

Thus my feeling is that the correlation is explained by possibilities 2 and 4.

[Mr Skeptic]

How about the possibility that

chronological age correlates with number of mutations, which can cause cancer.

and

carcinogens/mutagens cause mutations, which correlate with chronological age

 

The reason chronological age correlates with number of mutations is because mutations cannot be healed, so their number increases rather than decrease or staying the same. (assuming the mutation is not bad enough to kill the cell)

 

The reason mutations cause cancer is because 100% of cancer cells are mutant (but some mutant cells are not cancerous). You could say cancer is a type of mutation that results in cells reproducing uncontrollably and cells not loosing telomers.

 

This would also explain why carcinogens correlate with cancer, which your explanation does not account for.

 

--

 

Perhaps we should start talking about other aspects of aging. For example, why do trees live for so long, and do they have an age limit?

[Paralith]

To paralith

 

You are correct in that shortened telomeres reduce cell division - hence cancer. Where that argument breaks down is that a cancer cell undergoes a kind of cellullar regeneration, meaning all telomere bets are off! The fact is that older people suffer much more cancer than younger, meaning that telomere length as a factor is much outweighed by other factors, such as more cellular mutations, and reduced immune response. Thus age causes cancer, not preventing it.

 

That's what I'm saying, man. AGE does NOT prevent cancer. The shortening of telomeres does. For the sake of the argument, it doesn't matter that older people have more cancer than younger people. What matters is that by having telomerase not function in normal somatic cells, and by having other cancer-preventing genes functioning correctly, there is a greater chance that cancer can be held off until the organism has had a chance to successfully reproduce. As we all agree, as time goes on and mutations have a chance to occur, obviously a mutation that activates telomerase and/or de-activates a cancer preventing gene will most likely cause cancer to form. But hopefully by that time reproduction will have already occurred, and since anything that happens now is something evolution will effectively be blind to, the fact that the cancer-prevention mechanism will now cause your body to break down will not be selected against. So in this sense, aging/the breakdown of your body is a side effect of a cancer preventing mechanism.

 

This is, of course, assuming that the shortening of telomeres is in fact a mechanism to prevent cancer. We don't know that for sure, but I think it is definitely a plausible hypothesis.

[immortal]

Paralith I really don't agree with your hypothesis when the telomere length gets shorter cells usually die if they don't die then the chromosomes are ripped off in an ugly assortment leading to genomic instability, gene loss and cancer. This is in according to the Fusion model and an enzyme called exonuclease corresponds to gene loss. So there is a greater chance for a cell to go from normal to cancerous even though there is shortening of telomere. I think it is the checkpoints in a cell division which is important and ofcourse this is controlled dy cyclin dependant kinases and it is this mechanism which prevents cancer.

[lucaspa]

That's theorized as a molecular reason. I think what Mark wants to know is if there's an evolutionary advantage behind living long after your reproductive years are over (and are no longer passing down your genes). It's a very different question.

 

Presumably, the fact that we live along time is favored by evolution, otherwise we would have never evolved the mechanisms to live so long. It's not really energetically favorable from a evolutionary perspective.

 

1. There are genes that, if changed, will increase lifespan. This has been done in C. elegans and some other species. You can do a Google or PubMed search.

2. Telomeres seem to be responsible for what is called "Hayflick's Limit" in which cells have a specified number of cell divisions (which varies from species to species) and then they senesce and die. Note, however, that many adult stem cells do not have this limit and can replace their telomeres

3. There is a theory of aging that oxidative damage accumulates in cells and kills them.

 

In terms of evolution, natural selection is blind to what happens to an individual after it breeds. It cannot select either for longer or shorter lifespand UNLESS that lifespan has an effect on the ability of the next generation to breed. Thus, there are alleles in humans that protect against atherosclerosis, but they can't increase by natural selection since coronary artery disease only affects people long after they have children. So the alleles remain in low frequency in the population.

 

Paralith already gave the "grandmother theory" of why humans tend to be able to live so long after they have children. If anyone is interested, the paper is: Hawkes K. Am J Hum Biol. 2003 May-Jun;15(3):380-400.

Grandmothers and the evolution of human longevity. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12704714&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

 

Children whose grandmothers are still alive have a better survival chance than those whose grandmothers die young (like before they are born). And, of course, the longer a grandmother lives (and is active), the more grandchildren she is going to be around to help. So natural selection would select those who had longer-lived grandmothers (and, of course, they would have the grandmothers' alleles). Males go along for the ride since the alleles for longer lifespan are on chromosomes other than the X. This theory makes a lot of logical sense altho it is very difficult to test. One piece of data that it does explain is why women have longer average lifespans than men: women are directly selected while men only get an indirect benefit from selection for female long life.

 

And the reason we age is to prevent cancer. To have cancer you need two mutations in the same cell: the "immortality mutation" and the "reproduce uncontrollably mutation".

 

You are a bit behind the times in terms of theories of cancer origin. You are working under the old "two-hit hypothesis". It is now thought that most cancers arise in adult stem cells. These stem cells are ALREADY "immortal". What happens is that the stem cell loses growth control.

 

However, to have a clinical cancer the cell needs a lot more mutations: mutations that avoid apoptosis because it has genetic damage, mutations that avoid the immune system, mutations that attract blood vessels, and mutations that allow the cell to leave its tissue, get into the blood vessels, and then get out of the blood vessels again.

 

Avoiding the immune system is a biggie. It appears that most cancerous cells are killed by the immune system because they are producing abnormal proteins, and the immune system can detect this.

[SkepticLance]

To lucaspa

Yours was a good, informative post.

 

Just one small comment. In relaton to the 'grandmother' principle. It is not likely that males 'go along for the ride'. It is much more likely that male longevity was selected for according to a 'grandfather' principle. With chimps, the female has a much longer lifespan, for the simple reason that they are needed to raise offspring and males are not.

 

There is no reason why human lifespan evolution should have followed so different a path to chimps unless there was real selective pressure for long life to males. The selective pressure comes from the fact that a living, active grandfather is also an advantage to survival of grandchildren. This is seen by the interest that grandfathers show in their grandchildren.

 

And in tribal hunter-gatherer societies, grandfathers are active in hunting and gathering food for their grandchildren. Thus, having a living grandfather is a selective advantage. Don't be so hard on us males. We are not just 'along for the ride'. Human males play a vital role in helping their descendents survive.

[lucaspa]

Just one small comment. In relaton to the 'grandmother' principle. It is not likely that males 'go along for the ride'. It is much more likely that male longevity was selected for according to a 'grandfather' principle. With chimps, the female has a much longer lifespan, for the simple reason that they are needed to raise offspring and males are not. ... Don't be so hard on us males. We are not just 'along for the ride'. Human males play a vital role in helping their descendents survive.

 

You were doing well until you appealed to personal interest. Then you introduced the idea that your response is due to bias that you are male! (BTW, I am also male.)

 

The theory is what it is and the "grandmother" theory is that human males get their additional lifespan as a byproduct of selecting for the female lifespan. You are now arguing for a second theory: independent selection factors for male longevity.

 

Before modern health care, what was the difference in mean lifespan between men and women? If you can't do that, at least you can go back to the actuarial tables of 70 or so years ago. You are going to find that there was a considerable -- 25% -- difference. So how do you tell that from some direct selection pressure and the accidental benefit?

[Mr Skeptic]

You are a bit behind the times in terms of theories of cancer origin. You are working under the old "two-hit hypothesis". It is now thought that most cancers arise in adult stem cells. These stem cells are ALREADY "immortal". What happens is that the stem cell loses growth control.

 

Yes. I think that does show that the telomers are important in preventing cancer. Imagine if all your cells were immortal rather that just the relatively few stem cells.

 

However, to have a clinical cancer the cell needs a lot more mutations: mutations that avoid apoptosis because it has genetic damage, mutations that avoid the immune system, mutations that attract blood vessels, and mutations that allow the cell to leave its tissue, get into the blood vessels, and then get out of the blood vessels again.

 

I wouldn't know about that. All those mutations certainly make a cancer worse (malignant), but I don't know that they are necessary to have a cancer.

 

Avoiding the immune system is a biggie. It appears that most cancerous cells are killed by the immune system because they are producing abnormal proteins, and the immune system can detect this.

 

You mean most mutant cells. If a mutation changes the cell's proteins in the wrong way, especially the recognition of self proteins on the membrane, the immune system will destroy it. Even if it is not cancerous.

[SkepticLance]

lucaspa said

 

You are now arguing for a second theory: independent selection factors for male longevity

 

Actually, I am arguing for the same factors. Essentially the same evolutionary pressure for both male and female. I remember one thing the New Scientist article said.

" The real question is not why males do not live as long as females. The question is why they live almost as long."

 

Chimpanzees are more typical of primates. Males have short lives with a lot of reproduction in a short time. Females live longer, and the reason is very clear - they have to live longer to raise their offspring.

 

Male humans live almost as long as females. Why? For the same reason. Because they are important in the survival of the offspring. And this extends to the second generation.

 

Your comment about life spans 70 years ago do not change the basic principles here. If the lifespan gap was wider then, it makes little difference. Males were still living way beyond what was needed for basic reproduction.

[DrDNA]

However, to have a clinical cancer the cell needs a lot more mutations: mutations that avoid apoptosis because it has genetic damage, mutations that avoid the immune system, mutations that attract blood vessels, and mutations that allow the cell to leave its tissue, get into the blood vessels, and then get out of the blood vessels again.

Regarding the cancer cells leaving the tissue and migrating in and out of the blood vessels (or lymphatic system), you are describing metastasis. This usually happens in later stages of cancer, but it can happen anytime and it is not necessary for a malignant cell to metastasize to other parts of the body for it to be considered cancerous. It is however, much more dangerous after it begins to metastasize.

[Atlas]

When I think back to the original question, a thought comes to mind and that is the concept of entropy. Ultimately this has to play a huge role in the aging process of any living thing as the organization of cells struggles to fight the form destroying process that demands randomness. I could be way off base here, but it would seem to me that entropy would play a large role in aging right?

[Mr Skeptic]

Perhaps we should consider that in a sense, we don't really age. We are born from a cell that came from another cell that came from another cell... You could say that we are thousands of years old (or more). Cells seem to have the mechanisms to not age, but as organisms, we do age.