Why we age

[Pathfinder]

there is a very complex genetic control of aging involving interplay between a number of genes (not merely telomerase), all of which are working together to kill us after a certain period of time. We can influence some of the epigenetic and environmental aspects of the aging process, but we can’t escape the fact that we are genetically programmed to die.

Not exactly. First, there is no evidence that telomere shortening contributes to aging. Second, organisms in the wild do not die of aging, they die of extrinsic causes, thus there is no evolutionary pressure towards aging in one way or another. So aging cannot be programmed. Aging is just organisms wearing off.

there are 3 mechanism at work in our aging, homeostasis mechanism which were evolved to last only long enough, deleterious genes that will cause those homeostasis mechanism to fail after reproductive prime and finally the lack of homeostasis mechanism for indifferent survival.

We were built to last long enough to reach reproductive age and nothing more. There is no planned system failure, because there is no evolutionary pressure for that.

There are some cases of antagnositic pleiotropy in the body, that is a gene that is very useful in early life happens to become a burden when the organism lives long enough e.g. in captivity, but there is nothing planned about that. For example our stem cells cannot keep on replenishing our tissues indefinitely, becuse the p53, an anti tumor gene, suppresses proliferation.

if we were to live for thousands of years we would build up toxic metals like mercury in our body because of we lack of mechanism for removing them, we have nothing to protects us from several hundred to thousand of years of ingestion.

Young and healthy people can excrete heavy metals fast enough (yet its quite slow) so that no dangerous accumulation occurs in lower doses. When we get old and frail, the excretion becomes slower and slower, thus old people accumulate heavy metals in their body much easier.

 

[Hercules Rockefeller]

Not exactly. First, there is no evidence that telomere shortening contributes to aging.

Well, there is some, actually. For mammals much of it has come from telomerase knockout mice. These mice prematurely display some, but not all, of the pathophysiological traits of ageing. This goes to show that telomerase shortening plays a role, but not the sole role, in the ageing process.

Second, organisms in the wild do not die of aging, they die of extrinsic causes, thus there is no evolutionary pressure towards aging in one way or another. So aging cannot be programmed. Aging is just organisms wearing off.

You are incorrect. There are several genes that have been shown to affect ageing independently of environment. One that springs to mind immediately is the klotho gene that has been extensively studied in mice and humans. Mice deficient for the klotho gene product display a phenotype almost identical to human children with progeria (which causes children to age rapidly and to die, usually of heart failure, as early as 12 years). Up-regulating klotho in mice extends their lifespan.

Another experiment that springs to mind is research in C.elegans (nematode worms) where the researchers performed a series of genome-wide microarrays on worms at every stage of their lifecycle. These were worms that were kept in perfect laboratory conditions and displayed the organism’s maximum lifespan. They found that there was a genome-wide downregulation of homeostatic genes (eg. muscle maintenance, tissue repair and metabolism) towards the end of the organism’s lifespan. IOW, the worms’ own genome was killing them despite any extrinsic deleterious conditions. Their lifespan is only 2-3 weeks so it cannot be argued that mutation alone was reducing these gene functions.

I don’t have the references for any of these studies off hand, but they’re out there and should be easy to find it you’re interested.

There is a genetic ageing programme in most multicellular animals. This has been known for some time.

Edit: Ahh, I did have the C.elegans paper in my collection.

Genomic Analysis of Gene Expression in C. elegans
Hill et al.
Science Vol 290, 27 October 2000

 

[francois]

The reason is that there is a very complex genetic control of aging involving interplay between a number of genes (not merely telomerase), all of which are working together to kill us after a certain period of time. We can influence some of the epigenetic and environmental aspects of the aging process, but we can’t escape the fact that we are genetically programmed to die.

That's precisely what I'm talking about.

We are living, breathing objects created by genes which have limited functionality. There are only so many things we can be capable of. That's why we don't breathe fire at prey or breathe 02 underwater.

Development never stops. Gene expression is like a ticking clock. And there's a limited amount of variation in those genes out of which useful, salient traits can be carved. Your genes can make you exquisitely beautiful, but not much else. You can be amazingly intelligent, but probably not good looking or a good athlete *cough* Jews *cough*. You might develop earlier than others, but you probably won't develop as much. You can't have it all. The reason for this the limitation of genetics and the fact that variation is finite. Of course, some people do have it all, but those people are exceedingly rare. They are probably creations where all variation is used up to make him useful.

On the other hand, there are other creations which can only survive in the most lax environments. Those are the creations who are building up variation. White trash, I believe, is an example of this.

Ultimately our genes are tangled together and work on a clock using variation as food for usefulness. Some use that variation quickly; others don't. But ultimately it's going to run out and end with our individual death.

 

[Pathfinder]

Well, there is some, actually. For mammals much of it has come from telomerase knockout mice. These mice prematurely display some, but not all, of the pathophysiological traits of ageing. This goes to show that telomerase shortening plays a role, but not the sole role, in the ageing process.

These mice lose the integrity of highly proliferative tissues due to lack of stem cell availability, because their divisions are limited due to absence of telomerase. This doesn't happen in normal aging because in normal highly proliferative tissues telomerase is present. Also people with DKC (they have very little telomerase activity) present same symptoms, but you don't see these symptoms in normal people as they age.

Sources and further points to show that telomere shortening is not the cause of aging can be found in this blog post:

immortechnics.blogspot.com/2010/04/does-telomere-shortening-contribute-to.html

You are incorrect. There are several genes that have been shown to affect ageing independently of environment. One that springs to mind immediately is the klotho gene that has been extensively studied in mice and humans. Mice deficient for the klotho gene product display a phenotype almost identical to human children with progeria (which causes children to age rapidly and to die, usually of heart failure, as early as 12 years). Up-regulating klotho in mice extends their lifespan.

This doesn't mean that klotho gene's purpose is to cause aging in the organism.

Another experiment that springs to mind is research in C.elegans (nematode worms) where the researchers performed a series of genome-wide microarrays on worms at every stage of their lifecycle. These were worms that were kept in perfect laboratory conditions and displayed the organism’s maximum lifespan. They found that there was a genome-wide downregulation of homeostatic genes (eg. muscle maintenance, tissue repair and metabolism) towards the end of the organism’s lifespan. IOW, the worms’ own genome was killing them despite any extrinsic deleterious conditions. Their lifespan is only 2-3 weeks so it cannot be argued that mutation alone was reducing these gene functions.

It isn't established whether the downregulation is the cause or effect of aging. A completely normal metabolism accumulates all sorts of damage and this could induce downregulation of these genes directly or indirectly.

There is a genetic ageing programme in most multicellular animals. This has been known for some time.

Aging is not programmed. Genes regulate metabolism, which is not perfect and accumulates damage, which leads to aging and eventual death. Monkeying around with these genes could reduce the build up of some of this damage and thus postpone aging.

Again, you don't see organisms out in the wild dying of aging, which means any "aging genes" would vanish from the genome, because there is no purpose for them.

 

[Kennyc]

Based on the discussion the subject title is wrong.

The discussion seems to be about what makes us age?

Why we age is so that evolution can do it's work.

 

[francois]

Based on the discussion the subject title is wrong.

The discussion seems to be about what makes us age?

Why we age is so that evolution can do it's work.

How does aging help anything? I could see your point if you said dying helps evolution do its work. That could possibly be true.

We die because we age and it turns out to be helpful to evolution. I, as an adult, am capable of digesting milk, and that kicks ass. It's useful to me. Earlier humans didn't have that capability. We couldn't have evolved if we didn't have deaths to let in new people. But it doesn't mean that's the reason why we die.

 

[Kennyc]

How does aging help anything? I could see your point if you said dying helps evolution do its work. That could possibly be true.

We die because we age and it turns out to be helpful to evolution. I, as an adult, am capable of digesting milk, and that kicks ass. It's useful to me. Earlier humans didn't have that capability. We couldn't have evolved if we didn't have deaths to let in new people. But it doesn't mean that's the reason why we die.

Death is the result of aging, but it provides a timeframe for passing on knowledge.

Without death there is no evolution.

WHY we age is so evolution can work.

HOW we age is a different question which most of the discussion has been about.

 

[Pathfinder]

Yeah, the only problem is that organisms in the wild don't die of aging. Evolution is much more busier keeping organisms alive until reproductive age than killing them afterwards.

 

[soullust]

age what is this thing you speak of, i am 31 and i am one hot sexy as canadian man, i was when i was 21, and i will be when i am 71(if i am still here)

best way to prevent ageing is to take care of your self.

 

[Kennyc]

Yeah, the only problem is that organisms in the wild don't die of aging. Evolution is much more busier keeping organisms alive until reproductive age than killing them afterwards.

Mostly true, but death by old age is the final/unavoidable death.

 

[siledre]

I think your making it more complicated than it is.

 

[Kennyc]

I think your making it more complicated than it is.

Surely that's not directed at my comment is it. :shrug:

I don't know how much simpler it can be. And the simplest answer is generally the correct one.

 

[siledre]

Surely that's not directed at my comment is it. :shrug:

I don't know how much simpler it can be. And the simplest answer is generally the correct one.

was directed at the original post, sorry I hadn't read all the way down to your last comment.

 

[Kennyc]

was directed at the original post, sorry I hadn't read all the way down to your last comment.

Ah, confused me there for a second.

 

[Billy T]

How does aging help anything? ...

Yes, it keeps most young turks from killing old farts like me who would not kill themselves to make space for the next generation.

 

[Stoniphi]

Heh - and I am likely older than you. Us old farts are here due to the profit our progeny reaps from our continued presence.

Runners who go at least 50 miles a week typically stop the shortening of all of their muscle telemeres, many keep running into their 90's. Caloric restriction diets can extend life to 150% of normal expectations, at some cost.

How does this happen?

While your genes are like rungs on a ladder, the outer rails of that ladder contain exogenes that act like switches on the genes. They turn the genes off or on depending on environment. (acetilization vs, methylation)

Smoking tobacco methylates hystome bundles which shuts down genes that repair your lung tissues. Aerobic exercise acetilizes hystome bundles which turns on those same genes to repair your lungs. The difference is that you either develop lung cancer or not, despite your genetic potential, you still have the choice.

In short, you can make your healthy adult life longer or shorter depending on the personal choices that you make as you go along. There are a lot of other variables that come into play here as well, like attitude and overall life happiness.

I would support your choice to 'eat, drink, be merry, for tomorrow ye shall die' though, as l believe that this life is to be lived to the fullest and you should enjoy yourself as best you can while you are here.

 

[Jack_]

Death is the result of aging, but it provides a timeframe for passing on knowledge.

Without death there is no evolution.

WHY we age is so evolution can work.

HOW we age is a different question which most of the discussion has been about.

I thought evolution was caused by reproduction, random mutation and then natural selection.

I think you are arguing extintion causes evolution to the extinct species.

Do you have any mainstream papers that indicate the actual dying of an individual cause evolution?

Thanks

 

[Jack_]

Precisely!

Contrary to what many people on interweb science forums think, it’s not merely a matter of fiddling with telomerase expression. Upregulating telomerase in cultured cells can induce effective immortality, but this does not extend to whole vertebrate organisms. I don’t have the reference at hand but upregulating telomerase in mice only conferred about a 10% increase in lifespan in some mice but carried the risk of increased incidences of cancer leading to a decrease in lifespan for the majority. That’s not much better than simple calorie restriction (for the ones that survived to old age, that is).

The reason is that there is a very complex genetic control of aging involving interplay between a number of genes (not merely telomerase), all of which are working together to kill us after a certain period of time. We can influence some of the epigenetic and environmental aspects of the aging process, but we can’t escape the fact that we are genetically programmed to die.

If a species is a collection of cells and upregulating telomerase causes immortality, then why does the entire organism not experience immortality if all cells are upregulating?


Do you have any papers on this upregulation?

Thanks

 

[Stoniphi]

Hi there Jack, good to see you up and about.

While stopping the deterioration of telomere length enables effected cells to continue normal division & reproduction rather than dying, thus far this has been demonstrated in single cells on a petri dish and subgroups of cells in entire organisms only. I am unaware of success with preserving telomere structural integrity within the entirety of any organisms cells at this time. Thus, while said subgroup may well contribute to extending that organisms life span, the unaltered cells will eventually fail and cause the organisms demise.

The flaw is this assumption:

...all cells are upregulating..

 

[Pathfinder]

If a species is a collection of cells and upregulating telomerase causes immortality, then why does the entire organism not experience immortality if all cells are upregulating?

While stopping the deterioration of telomere length enables effected cells to continue normal division & reproduction rather than dying, thus far this has been demonstrated in single cells on a petri dish and subgroups of cells in entire organisms only. I am unaware of success with preserving telomere structural integrity within the entirety of any organisms cells at this time. Thus, while said subgroup may well contribute to extending that organisms life span, the unaltered cells will eventually fail and cause the organisms demise.

I don't think telomeres have anything to do with aging:

immortechnics.blogspot.com/2010/04/does-telomere-shortening-contribute-to.html

Caloric restriction diets can extend life to 150% of normal expectations, at some cost.

Caloric restriction might be overrated:

immortechnics.blogspot.com/2010/03/caloric-restriction-reality-check.html