A Theory For Why We Age!

[MarkSD]

Hello everyone,

 

One thing that is of great interest to me is why exactly it is that animals (including humans) age. After all, a species as a whole manages to survive for a large number of generations without significant mutation or chromosomal damage. So why is it that animals after they have been alive for a certain period of time experiance the symptoms associated with senescence?

 

One theory that has been put forward to explain the conundrum of why we age, is known as The Evolutionary Theory of Ageing. This is how it works.

The Evolutionary theory of ageing (developed by William Hamilton in association with several other researchers), is the classical theory of why humans live so long after their reproductive age is effectively over. The theory (as was previously discussed) proposes that animals generally die shortly after reproducing due to the fact that lingering for any longer would not lead to any greater numbers of surviving offspring – thought to be the only model for success evolutionarily speaking.

 

For more on The Evolutionary Theory of Ageing, see the following link:

 

http://URL REMOVED! AGAIN!

 

Any thoughts?

 

Mark

[ydoaPs]

I thought it had something to do with the shortening of telomeres as cells divide.

[ecoli]

I thought it had something to do with the shortening of telomeres as cells divide.

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.

 

However, to assume this may be ignoring modern medicine and health care. And the effect is has on the phenotypic plasticity of living to old ages. It could be, humans really didn't live that long past reproductivity, but not because it's encoded in our genotype. If that particular phenotype was never expressed, it couldn't get selected against.

[Paralith]

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.

 

However, to assume this may be ignoring modern medicine and health care. And the effect is has on the phenotypic plasticity of living to old ages. It could be, humans really didn't live that long past reproductivity, but not because it's encoded in our genotype. If that particular phenotype was never expressed, it couldn't get selected against.

 

There is one theory that says humans evolved relatively longer lifespans for the purpose of multi-generational child care - in other words, grandma can still contribute to her reproductive success by helping take care of her grandchildren. And considering the relatively large amount of time and effort required to successfully rear a human child, probably any extra help the parents can get will make a difference. And I say relatively longer lifespans, because obviously today's medical advances have increased our lifespans considerably. Still, even before then, we did tend to live longer than most other mammals.

[Mr Skeptic]

I thought it had something to do with the shortening of telomeres as cells divide.

 

Yes, that seems to be the mechanism for aging.

 

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". The "reproduce uncontrollably mutation" is the one that actually causes the cancer. But if it only had that one, then the telomer mechanism would eventually ensure that the line of cells dies, killing the cancer. The probability of getting both mutations is quite low, hence you are that much less likely to get cancer. If you were to have all your cells without the telomer shortening mechanism, then you wouldn't age in this respect (other damage would accumulate anyhow), and you would be very likely to get cancer (as you need only one mutation rather than two).

[ecoli]

There is one theory that says humans evolved relatively longer lifespans for the purpose of multi-generational child care - in other words, grandma can still contribute to her reproductive success by helping take care of her grandchildren. And considering the relatively large amount of time and effort required to successfully rear a human child, probably any extra help the parents can get will make a difference. And I say relatively longer lifespans, because obviously today's medical advances have increased our lifespans considerably. Still, even before then, we did tend to live longer than most other mammals.

 

that makes sense... we share 1/8 of our genome with grandchildren, right? So helping to raise 4 grandchildren would be like raising 2 children (from a basic evolutionary perspective).

 

So I guess that would fall under kin selection and altruistic theory.

[foodchain]

Yes, that seems to be the mechanism for aging.

 

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". The "reproduce uncontrollably mutation" is the one that actually causes the cancer. But if it only had that one, then the telomer mechanism would eventually ensure that the line of cells dies, killing the cancer.

 

Cancer can come from or be triggered by more then just abnormal behavior of a cell or group of cells. For instance, asbestos. So did the cells that become cancerous from asbestos rely on the proposed mechanism? Then again if cancer was known to some form of adaptive or fixed immunity of an organism to be environmental for instance, how would it know and overall how does such related to NKC behavior?

 

Lastly from a molecular viewpoint biodiversity suggests that this can evolve also in a manner not so “mathematically” acute. Such as why do some species posses a type of RNA we don’t? To a better example of why do prokaryotes look the way they do compared to Eukaryotes, and why have eukaryotes become more prone to evolve? What I am trying to get at here is the molecular mechanism in question might simply be around because it worked and never was selected against overall, which means also its only reason for existence could be just that, not that its a smashing success, just that it made it and or can function.

[Mr Skeptic]

What I am trying to get at here is the molecular mechanism in question might simply be around because it worked and never was selected against overall, which means also its only reason for existence could be just that, not that its a smashing success, just that it made it and or can function.

 

That's pretty much what I'm saying. Obviously, single-celled creatures can't have telomers getting shorter, or their whole line would die out when they ran out of telomers. So they only make sense for multicellular creatures. And their purpose would seem to be to prevent cancer. Maybe they have another purpose too, but I don't know of it.

[SkepticLance]

There are a number of theories as to why humans age. here are a few.

 

1. Evolution creates ageing genes to elimate maladapted individuals, so they cannot contribute their genes to the population. In a changing environment, the gene pool must change, and individuals adapted to a different environment must go.

 

2. The genes for ageing are harmful mutations that take effect only with greater age. Since they act long after normal reproduction has already happened, they are not eliminated by natural selection. Over a period of a billion years or more, these harmful genes have accumulated, till there are now enough to age and kill every individual in time. We already know that the rate of elimination of harmful mutations from the population depends on when they affect individuals. Genes like Progeria, which cause harm before puberty are eliminated quickly - one generation. Genes that kill after puberty, like hemophilia, take a number of generations to be totally eliminated. Genes like Huntingtons which kick in after age 40, may take 100 or more generations to be eliminated. It is reasonable to suspect that harmful genes that have an effect only after, say, age 50, may never be eliminated.

 

3. The mitochondria are the source of ageing. These are the energy producers of the cells, and they have their own nucleic acids, which produce their own respiratory enzymes. As time goes by, more and more mitochondria develop harmful mutations. As a higher percentage of the mitochondria in the human body become less able to produce energy, the body's processes slow down. Laboratory studies have shown that mitochondria do, in fact, suffer such defects over time. This is reversed in reproduction by a selection process. The defective mitochondria are eliminated, and only unspoiled ones can become part of a human ova. Thus, a new embryo begins with a clean slate.

 

and so on.

[Dak]

Any thoughts?

 

Yes. Stop linking to that website. You've allready been told twice, out of your 4 posts here.

[Silverspeed]

There are a number of theories as to why humans age. here are a few.

 

1. Evolution creates ageing genes to elimate maladapted individuals, so they cannot contribute their genes to the population. In a changing environment, the gene pool must change, and individuals adapted to a different environment must go.

 

2. The genes for ageing are harmful mutations that take effect only with greater age. Since they act long after normal reproduction has already happened, they are not eliminated by natural selection. Over a period of a billion years or more, these harmful genes have accumulated, till there are now enough to age and kill every individual in time. We already know that the rate of elimination of harmful mutations from the population depends on when they affect individuals. Genes like Progeria, which cause harm before puberty are eliminated quickly - one generation. Genes that kill after puberty, like hemophilia, take a number of generations to be totally eliminated. Genes like Huntingtons which kick in after age 40, may take 100 or more generations to be eliminated. It is reasonable to suspect that harmful genes that have an effect only after, say, age 50, may never be eliminated.

 

3. The mitochondria are the source of ageing. These are the energy producers of the cells, and they have their own nucleic acids, which produce their own respiratory enzymes. As time goes by, more and more mitochondria develop harmful mutations. As a higher percentage of the mitochondria in the human body become less able to produce energy, the body's processes slow down. Laboratory studies have shown that mitochondria do, in fact, suffer such defects over time. This is reversed in reproduction by a selection process. The defective mitochondria are eliminated, and only unspoiled ones can become part of a human ova. Thus, a new embryo begins with a clean slate.

 

and so on.

 

You got a point you know?

[foodchain]

The resetting of a molecular clock so to speak occurs also in developmental processes. The problem I have with this is it explains something that can be reflected by behavior not of just this aspect of an organism with such if it exists for that purpose. The problem I see then is why so many similar behaviors that vary a little of course but go along the same lines of thought being put forward here exist in some form in differing aspects. So what is that to mean, did this aspects carry on similar function or face similar selection pressures and in short become what they are by a means of co-evolution? A simple example is a natural killer cell here with a quote from wiki.

 

"Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte which constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis."

 

Thusly named little beasties. So how does this relate to the topic at hand as somatic cells can also undergo variation all through the body over a lifespan, in which case I don’t doubt some become cancerous, but how does a telomere then react to such a situation? Does the telomere actually do anything special at that point in time, and again how does it know.

 

If per say by the simple fact its involved in aging as related to DNA and its processes, well some species it would seem telomere has varying degrees of effectiveness in roles commonly talked about here.

 

In reference to mr.skeptic the pro to eu was a multifaceted response. In that such behavior seems similar to plasmid behavior and or introns if related. so I was going on about such in it might have something to do with telomeres existence. The other point is that prokaryotes don’t evolve like eukaryotes, and why exactly?

[Paralith]

So how does this relate to the topic at hand as somatic cells can also undergo variation all through the body over a lifespan, in which case I don’t doubt some become cancerous, but how does a telomere then react to such a situation? Does the telomere actually do anything special at that point in time, and again how does it know.

 

There is an enzyme which rebuilds telomeres, called telomerase. However, in most normal cells, it is not expressed; the gene for telomerase is turned off. In cancer cells, the gene gets turned on. The gene is also turned on in embryonic stem cells and in other cell lines that need to divide very often, but other than that, most somatic cells do not express it.

[foodchain]

There is an enzyme which rebuilds telomeres, called telomerase. However, in most normal cells, it is not expressed; the gene for telomerase is turned off. In cancer cells, the gene gets turned on. The gene is also turned on in embryonic stem cells and in other cell lines that need to divide very often, but other than that, most somatic cells do not express it.

 

Yes but how does the telomeres again respond exactly to killing cancer and how does it know to do this as proposed?

 

Abstract

Untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge, but deregulated expression of a single multi-component enzyme, telomerase, is implicated as a causative factor for immortalization in the vast majority of human tumors. This review highlights the potential of telomerase as a target for novel cancer gene therapies.

 

Rapid advances in our understanding of the molecular basis of cancer development and progression over the past three decades have led to the design of new potential cancer therapies. High throughput target validation and expression studies are expected to yield a powerful arsenal of new cancer treatments, but untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge. A considerable body of evidence in recent years implicates deregulated expression of a single multi-component enzyme, telomerase, as a causative factor at the heart of immortalization in the vast majority of human tumors. This review highlights the potential of telomerase as a target for novel cancer therapies. The potential of exploiting the selectivity of the telomerase family of genes within cancer cells to develop gene therapy strategies is discussed, and the progress towards translating these novel therapeutics from the laboratory to the clinic is reviewed.

 

http://eprints.gla.ac.uk/982/

 

 

The only idea I can get is overall ageing then is to be a product to end cancer as "normal" genetic or genomic produces go about. I don’t see how the connection can really be made as prokaryotes also die out and thusly does all life. Which of course this whole process then has to apply to reproduction to a great deal. Also there seems to be more then one strategy to combat cancer by the body.

[Mr Skeptic]

The resetting of a molecular clock so to speak occurs also in developmental processes. The problem I have with this is it explains something that can be reflected by behavior not of just this aspect of an organism with such if it exists for that purpose. The problem I see then is why so many similar behaviors that vary a little of course but go along the same lines of thought being put forward here exist in some form in differing aspects. So what is that to mean, did this aspects carry on similar function or face similar selection pressures and in short become what they are by a means of co-evolution? A simple example is a natural killer cell here with a quote from wiki.

 

"Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte which constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis."

 

Thusly named little beasties. So how does this relate to the topic at hand as somatic cells can also undergo variation all through the body over a lifespan, in which case I don’t doubt some become cancerous, but how does a telomere then react to such a situation? Does the telomere actually do anything special at that point in time, and again how does it know.

 

If per say by the simple fact its involved in aging as related to DNA and its processes, well some species it would seem telomere has varying degrees of effectiveness in roles commonly talked about here.

 

In reference to mr.skeptic the pro to eu was a multifaceted response. In that such behavior seems similar to plasmid behavior and or introns if related. so I was going on about such in it might have something to do with telomeres existence. The other point is that prokaryotes don’t evolve like eukaryotes, and why exactly?

 

Teleomeres are basically just a way for cells to count how many times they have reproduced, and to make sure that they stop reproducing after so many generations. The mechanism is pathetically simple. Telomers are chucked off every time a cell reproduces, and when it runs out of telomers it starts loosing coding DNA. Then it will die out or be noticed a mutant by the immune system or itself. An enzyme called telomerese will regenerate the telomers in some cell lines so your kids don't die of old age at birth.

 

So if a single cell becomes tumerous but does not regenerate telomers, it will start to reproduce uncontrollably, but will lose telomers. The number of telomers it has specifies how many times it can reproduce, and therefore how big it can grow, before it runs out of telomers and dies. If one of these starts regenerating telomers, you get cancer that won't stop growing.

 

As for prokaryotes and eukaryotes, they are built differently. Eukaryotes have some independent organelles, some of which have their own DNA separate from your own DNA. So us eukaryotes are more modular, so it would make sense that they could be easier to modify without killing. Prokaryotes are also tiny and (I think) faster reproducing, so that could have an effect too. Prokaryotes have a huge pressure to reproduce as fast as possible.

[foodchain]

Teleomeres are basically just a way for cells to count how many times they have reproduced, and to make sure that they stop reproducing after so many generations. The mechanism is pathetically simple. Telomers are chucked off every time a cell reproduces, and when it runs out of telomers it starts loosing coding DNA. Then it will die out or be noticed a mutant by the immune system or itself. An enzyme called telomerese will regenerate the telomers in some cell lines so your kids don't die of old age at birth.

 

So if a single cell becomes tumerous but does not regenerate telomers, it will start to reproduce uncontrollably, but will lose telomers. The number of telomers it has specifies how many times it can reproduce, and therefore how big it can grow, before it runs out of telomers and dies. If one of these starts regenerating telomers, you get cancer that won't stop growing.

 

As for prokaryotes and eukaryotes, they are built differently. Eukaryotes have some independent organelles, some of which have their own DNA separate from your own DNA. So us eukaryotes are more modular, so it would make sense that they could be easier to modify without killing. Prokaryotes are also tiny and (I think) faster reproducing, so that could have an effect too. Prokaryotes have a huge pressure to reproduce as fast as possible.

 

The behavior of what you are talking about is weakly active in somatic cells to a larger degree then what you are alluding to. The other reality again is you say ageing is to combat cancer and that’s why telomeres exist. I say how can you know this?

 

I say with just about as much proof because I am just saying it that telomeres and ageing is just a normal part of biological processes that came about and have not been selected against directly. This is a rather core aspect do DNA and seems to be prevalent even while the behavior of telomeres can vary in species. So its just as easy to assume that ageing or how a genome was operating with this procedure never had that particular aspect selected against, or that ageing was never selected against. For instance a octopus has a very short lifespan? Does this mean the octopus is highly cancerous or cancer prone? Or simply did natural selection again not really act on this process directly, or even allowed it.

 

As for pro to eu, the reality as I see it is you don’t see any species like a duck or a boar or anything larger then a single cell really that is prokaryote based on a cellular level. That means something occurred obviously from pro to eu that allowed for multicellular, thusly I think a prime factor of current evolution of life on earth. So using evolution to figure this out could probably help explain a lot, such as what was it on the cellular/molecular scale exactly?

[Mr Skeptic]

OK, so I don't actually know for sure that telomeres are to prevent cancer, but that is what I usually hear. Got any better ideas why we hit the self-destruct button when we obviously can still benefit from living longer?

[bascule]

Leading longevity researcher Aubrey de Gray has identified 7 primary causes of aging:

 

http://www.livescience.com/health/050411_aubrey_interview.html

 

Nuclear Mutations/Epimutations

These are changes to the DNA, the molecule that contains our genetic information, or to proteins which bind to the DNA. Certain mutations can lead to cancer.

 

Mitochondrial Mutations

Mitochondria are components in our cells that are important for energy production. They contain their own genetic material, and mutations to their DNA can affect a cell's ability to function properly.

 

Intracellular Junk

Our cells are constantly breaking down proteins that are no longer useful or which can be harmful. Those proteins which can't be digested simply accumulate as junk inside our cells.

 

Extracellular Junk

Harmful junk protein can also accumulate outside of our cells. The amyloid plaque seen in the brains of Alzheimer's patients is one example.

 

Cell Loss

Some of the cells in our bodies cannot be replaced, or can only be replaced very slowly.

 

Cell Senescence

This is a phenomenon where the cells are no longer able to divide. They may also do other things that they're not supposed to, like secreting proteins that could be harmful.

 

Extracellular Crosslinks

Cells are held together by special linking proteins. When too many cross-links form between cells in a tissue, the tissue can lose its elasticity and cause problems.

[ajman2463]

It seems to me like you guys are drifting off into physcology mixed with your biology. Physically, the reason we age and eventually die is our telemers shortening until they are gone (then we die) and the fact that everytime our DNA is copied during mitosis it develops errors, (mutations). I've personally never heard of an entire species evolving to protect against one specific disease (cancer). And the fact is that teenage kids cannot raise kids in our new technological world. Thats a social problem, not a biological one. Cancer and the inability to raise kids is something we fear, and not our bodies, if that makes sense, so our bodies dont prepare for these things.

 

Something else is, in my OPINION, is that cancer is not a naturally occuring thing. it is the affect of human inventions that emit radiation and the toxic molecules we create and expose ourselves to, like old insulation, and high-energy producing waves.

[Paralith]

It seems to me like you guys are drifting off into physcology mixed with your biology. Physically, the reason we age and eventually die is our telemers shortening until they are gone (then we die) and the fact that everytime our DNA is copied during mitosis it develops errors, (mutations). I've personally never heard of an entire species evolving to protect against one specific disease (cancer). And the fact is that teenage kids cannot raise kids in our new technological world. Thats a social problem, not a biological one. Cancer and the inability to raise kids is something we fear, and not our bodies, if that makes sense, so our bodies dont prepare for these things.

 

Something else is, in my OPINION, is that cancer is not a naturally occuring thing. it is the affect of human inventions that emit radiation and the toxic molecules we create and expose ourselves to, like old insulation, and high-energy producing waves.

 

Cancer is indeed naturally occuring, and it is more likely to happen the longer you live; aka, your cells have divided more and more allowing more and more chances for a mutation to occur. And since cancer can kill you and can most certainly impede your ability to both have children and successfully raise them, it makes sense the we may have evolved mechanisms to counteract oncogenesis.

[SkepticLance]

The idea that ageing is an adaptation to combat cancer makes no sense at all. If so, we would expect older people to be more cancer resistant. In fact, the reverse applies. A 75 year old has 100 times the chance of developing cancer within 12 months compared to a 25 year old.

 

Thus, the best defense against cancer is to stay young, not grow older.

 

You should realise, that in terms of evolutionary success, to grow old and die is not a failure. As long as reproduction occurs and the genes are passed on, that ageing and dying individual is an evolutionary success. Protecting against cancer is only an advantage if it happens in the youthful reproductive years. Ageing to provide protection is kind of pointless.

[bascule]

Physically, the reason we age and eventually die is our telemers shortening until they are gone (then we die)

 

That's one of many causes, and therapy with telomerase (an enzyme which reconstructs telomeres) never bore out the initial expectations... that's why all the initial media buzz about using it for aging therapy simply died down and we've heard little since. It is, however, listed by leading longevity researcher Aubrey de Gray as one of the causes of aging (cell senescence)

 

The only clinically proven method of life extension, caloric restriction, operates on the mitochondria, and the specific mechanism by which it extends life is currently the subject of intense research.

 

Life extension therapy will need to target multiple causes of aging. There's no single cause nor silver bullet.

[foodchain]

Cancer is indeed naturally occuring, and it is more likely to happen the longer you live; aka, your cells have divided more and more allowing more and more chances for a mutation to occur. And since cancer can kill you and can most certainly impede your ability to both have children and successfully raise them, it makes sense the we may have evolved mechanisms to counteract oncogenesis.

 

Its not only that but the reality that the specific aspect in question is present in such a diverse amount of eukaryotic life but yet the concept of life span at least in the wild does not suggest heavy activity of this item in the concept of aging as a mode to combat cancer primarily at least. I mean do some species of turtles and or plants just somehow molecular wise know that they are cancer proof or something?

 

I don’t know the extent of function as single entity can take on overall but I just currently don’t see a lot of merit supporting such as a strong factor in ageing in reference to combating cancer. Plus the activity of such is not zero in somatic cells lacking cancerous traits, for however also such is to know why difference is equal to cancer on a cellular/molecular scale.

 

Humans did not evolve to travel into space I would say, but they do anyways. I guess the point I am trying to make is how do you determine to an exact amount the impact of natural selection, such as weak to strong selective pressures in any regard to the reason of existence for aspects of a biological entity. I mean what if we could turn off stress in a human mind? Stress also has negative health consequences but currently seems to be needed I would imagine.

 

Something I have noticed is if I reduce on artificial flora on my own property and allow native forms of such to return, so does many species of the local fauna, which I am sure has a molecular basis right?

[Mr Skeptic]

The idea that ageing is an adaptation to combat cancer makes no sense at all. If so, we would expect older people to be more cancer resistant. In fact, the reverse applies. A 75 year old has 100 times the chance of developing cancer within 12 months compared to a 25 year old.

 

Thus, the best defense against cancer is to stay young, not grow older.

 

You should realise, that in terms of evolutionary success, to grow old and die is not a failure. As long as reproduction occurs and the genes are passed on, that ageing and dying individual is an evolutionary success. Protecting against cancer is only an advantage if it happens in the youthful reproductive years. Ageing to provide protection is kind of pointless.

 

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.

[SkepticLance]

To Mr. Skeptic

 

What I said still applies. Ageing cells can still go cancerous and form a tumour. In fact, this happens far more often in aged individuals than in young individuals.