149 replies to this topic

[HighDesertWizard]

Absolutely, this is a programmed change, just as the body's development from embryo to adult is finely programmed. What is in question is whether or not aging is programmed, and although HSPR shutdown contributes to aging it does not mean this is its programmed purpose.

I agree.

An Epigenetic Turn related specifically to the decline of the Heat Shock Response does not necessarily mean that aging after that Turn is "programmed" or that there is an emergent purpose in that Turn.

And about Programmed Aging...

It has been demonstrated thru attempts at Falsification that significant survival probability-related functions of The Inflammatory Reflex have been conserved in humans.

The first studies about The Inflammatory Reflex were published between 2002 and 2006 and include studies that show significant increases in survival probability by triggering it.

 

 

 

 

 

 

IMO, any program theory of aging that doesn't account for the survival curves and demonstrated mechanism, TIR, in the pics above cannot be taken seriously.

Edited by HighDesertWizard, 11 December 2018 - 04:39 PM.

[OP2040]

Positive death programs do exist in semelparous species, so I'm not necessarily willing to give up on the idea.  I'm just saying it is also plausible that it is the stopping of the youthful developmental program that constitutes the onset of aging. 

 

There is some evidence out there of a positive aging program that would need to be alternatively explained.  Namely during parabiosis.  In iterparous species, parabiosis is clearly anti-aging.  However, it is not just one way, with youth factors promoting youthfulness.  The obverse is also true.  There is some element in aged blood that actively ages young receivers. This is more likely to be a signalling mechanism in both cases than it is just transferring healthy or damaged tissue because if it were damaged tissue, a youthful micro-environment should be able to clear it no problem.

[Rocket]

Absolutely, this is a programmed change, just as the body's development from embryo to adult is finely programmed. What is in question is whether or not aging is programmed, and although HSPR shutdown contributes to aging it does not mean this is its programmed purpose.

 

Without evidence, that is hypothesis. To be able to prove programming is akin to proving god. I posit that what people call programming is just cells developing, growing, dividing, dying and becoming dormant. It may seem orchestrated as if by design, but it is not. It is natural selection that happened to arrange cells in such and such a manner. Over the eons some cells organized in manners that led to their demise, hence those combinations are not in existence. Some combinations thrived and exist today. No plan. Natural selection. Everything operating within the physics of the principle of least action, or Lagrangian and Hamiltonian principles.

 

To call it programmed, requires a programmer with a master plan. 

Edited by Rocket, 11 December 2018 - 04:45 PM.

[OP2040]

Calling something a "program" does not require a programmer.  Now I see your objection has more to do with metaphysics than science.  Does creation require a "creator"?   

 

Calling it "programmed" is a just a linguistic convenience, no one implying a programmer unless you consider the evolutionary process a programmer.

Edited by OP2040, 11 December 2018 - 04:57 PM.

[Rocket]

Calling something a "program" does not require a programmer.  Now I see your objection has more to do with metaphysics than science.  Does creation require a "creator"?   

 

Calling it "programmed" is a just a linguistic convenience, no one implying a programmer unless you consider the evolutionary process a programmer.

 

No my argument is not based on a metaphysical argument. My argument is clearly written above... some cells organized in ways that led to the life forms we see today. Some cells organized in ways that led to nothing. Everything based on the principles of Hamiltonian and Lagrangian principles. 

 

I'm trying to cause people to be precise in their terminology. A program requires a programmer, and a plan. If there is no programmer and no plan, it is not a program. 

 

When someone says something to the effect that "Look at a developing embryo, it must surely be following a program." That is false. No one programmed the embryo with a plan to develop in an adult. Its a random collection of cells, all doing their individual cellular things, that just so happen to lead to a viable life form. What may be appear to be organized and planned is just randomness (another principle of quantum mechanics).

 

The very question itself of "Is ageing programmed" is incorrect.

 

If you have a program, you have a plan, and you have something that created the program. And that is not the case. Random events happen all the time. Some people are born with autism, and others are born missing limbs. Some embryos split into two and three and there twins and triplets.

 

I see people make claims, "Nature is trying to kill us." Nature is not trying to do anything at all. 

Edited by Rocket, 11 December 2018 - 05:39 PM.

[OP2040]

It used to be thought that CR worked because metabolic damage is reduced.   This idea is so intuitively powerful that a lot of people still slip back into that way of thinking.  But CR works entirely through gene expression, to ramp up repair mechanisms to a more youthful state.

 

Here, fresh off the presses is another example of this common confusion.  We have long known that cold temperature can be an anti-aging strategy  The intuitive idea here would be that it lowers thermodynamic damage.  Well, turns out that's wrong, once again certain protective genes are turned on and possibility others turned off.  In this case if you don't have the genes or the ability to express them, then cold therapy is probably pointless and it does nothing with regard to damage.

 

https://phys.org/new...enetically.html

 

This is no small distinction and probably one of the reasons the man on the street doesn't even want to think about aging.  Their current conception is that it is caused by damage and the best you can possibly do is minimize that damage with a handful of terrible options like not eating, taking cold showers, and engaging in almost no pleasurable activity.  No wonder we have a PR problem, that makes death sound not so bad to most people.

[OP2040]

This is just silly.  Then does "development" require a "developer"?  Those cells you talk about that are "organized", where's the "organizer"?

[xEva]

Yes xEva, evolution certainly favors turning the HSP response down in adulthood. I'm sure animal populations in the wild do better because of this, otherwise it wouldn't happen, but there is not enough evidence to say for sure that this is due to the inducement of faster aging (and pop turnover) or a tradeoff with some other fundamental attribute.

 

For example it might well be that it is very important to grow to adulthood without any errors in protein folding, but once you're grown the growth and repair pathways can afford to be sloppier but faster, perhaps, and this offers survival advantages?

 

??? "once you're grown the growth and repair pathways can afford to be sloppier but faster, perhaps, and this offers survival advantages?

 

Faster, definitely no. But sloppy repair pathways is what leads to "aging". Aging is characterized by accumulation of damaged proteins. Damaged proteins are not only toxic, they impede the normal functioning of the cell and can lead to its death.

 

The only "survival advantages" sloppy repair pathways offer are to the germ line, coz this ensures inevitable death of each individual.

 

And it's not just heat shock response that goes down. Here is the quote from the same paper:

 

Aging has long been thought to contribute to the onset of many degenerative diseases associated with protein misfolding as exemplified by neurodegenerative disorders. Yet, even for these pathologies it is uncertain whether an age-associated decline in protein quality control pathways represents a parallel or causative event. Here we show that multiple cell stress responses, highlighted by a dramatic collapse of the HSR, are severely compromised at an early point in adulthood that is associated with fecundity. This repression of cell stress responses has profound consequences on stress resilience during adulthood and organismal lifespan, and may leave adults more vulnerable to disease.

 

They measured multiple stress response pathways before and after the onset of reproduction, not just HSR.

 

Using a combination of genetic and biochemical approaches we found that the global repression of stress responses is controlled by signals from germ line stem cells  <-- plural 'stress responses'

 

They only focused specifically on HSR to trace the signal all the way from its origin to how exactly it affected the transcription of HSP-1.

Edited by xEva, 12 December 2018 - 01:16 AM.

[sthira]

Maybe repairing broken parts assists with alteration to the program (if that's what aging belongs is, I'm not sure). But when I see active, healthy women, for example, who've had hips replaced, I see something else change, too. Not imaginary changes -- a real difference. With hip successful surgery, they may have regenerated something inside, too, beyond just the bones. An inner light may return, a confidence, stability, the flow of a certain sense of ease they'd lost because of the broken hip's pain. When pain is lifted, stabilities in motion are restored, literally step by step, and normalcy of familiar alignment returns, lives get transformed. I'd say a program was changed, too.

Not for everyone -- definitely generalizing here, lots of people get injured and don't come all the way back to prior health, they can't or they don't want to. I def see people -- mainly women -- who've had loads of inner and outer "work done" in my profession. I ain't no authority whatsoever, just observing that when the fix-it results are good, they can be very good. And VG means invisibility -- you won't know what was done unless she (or he) tells you. You might sense it, though.

The cosmetic errors are often easy to see, but high quality work isn't so easy to see. People now can just -- look better. But looking better isn't always looking younger -- there's a distinction -- looking better is just looking better. And often looking better is better than looking younger.

Same things may be happening to the program on the inside -- that ankle or knee or thumb that was repaired, toes are frequently fixed, heels, feet -- those are real changes that change motion patterns back to healthier states. Like duh, the spine is trickier to fix, the neck -- but when some osteo-repairs are good, they may change up that mutable aging program, too.

[QuestforLife]

??? "once you're grown the growth and repair pathways can afford to be sloppier but faster, perhaps, and this offers survival advantages?

 

Faster, definitely no. But sloppy repair pathways is what leads to "aging". Aging is characterized by accumulation of damaged proteins. Damaged proteins are not only toxic, they impede the normal functioning of the cell and can lead to its death.

 

The only "survival advantages" sloppy repair pathways offer are to the germ line, coz this ensures inevitable death of each individual.

 

And it's not just heat shock response that goes down. Here is the quote from the same paper:

 

Aging has long been thought to contribute to the onset of many degenerative diseases associated with protein misfolding as exemplified by neurodegenerative disorders. Yet, even for these pathologies it is uncertain whether an age-associated decline in protein quality control pathways represents a parallel or causative event. Here we show that multiple cell stress responses, highlighted by a dramatic collapse of the HSR, are severely compromised at an early point in adulthood that is associated with fecundity. This repression of cell stress responses has profound consequences on stress resilience during adulthood and organismal lifespan, and may leave adults more vulnerable to disease.

 

They measured multiple stress response pathways before and after the onset of reproduction, not just HSR.

 

Using a combination of genetic and biochemical approaches we found that the global repression of stress responses is controlled by signals from germ line stem cells  <-- plural 'stress responses'

 

They only focused specifically on HSR to trace the signal all the way from its origin to how exactly it affected the transcription of HSP-1.

 

This is a fascinating paper - no argument. The missing piece however, is WHY the stress response(s) are turned down. Is it to accelerate aging and increase population turnover (and genetic variation) as proposed by Mitteldorf and co., or is it done because it offers a shorter term advantage to the animal (but at the cost of faster aging).

 

Proponents of programmed aging need to prove it is the former, but this is a formidable task.

[xEva]

This is a fascinating paper - no argument. The missing piece however, is WHY the stress response(s) are turned down. Is it to accelerate aging and increase population turnover (and genetic variation) as proposed by Mitteldorf and co., or is it done because it offers a shorter term advantage to the animal (but at the cost of faster aging).

 

Proponents of programmed aging need to prove it is the former, but this is a formidable task.

 

 

oh! now I understand your previous post. Until now I could not imagine that someone could assume even for a moment that being less fit may be advantageous to an animal's survival. The only such animal I know of is a kid playing hooky so that he would not have to go to school and perhaps learn  about the importance of stress resistance on fitness. In fact in some schools of thought fitness and stress resistance are held synonymous.

 

and why "accelerate aging"?  If the main feature of aging is accumulation of damaged proteins this is what directly causes it.

 

And you saying that getting old "offers a shorter term advantage" -? What sort of advantage could it be?

 

 

I'm amazed at what lengths people are willing to go just to protect their long-held believes. Why the idea of programmed aging is to abhorrent to you guys?

[QuestforLife]

oh! now I understand your previous post. Until now I could not imagine that someone could assume even for a moment that being less fit may be advantageous to an animal's survival. The only such animal I know of is a kid playing hooky so that he would not have to go to school and perhaps learn  about the importance of stress resistance on fitness. In fact in some schools of thought fitness and stress resistance are held synonymous.

 

and why "accelerate aging"?  If the main feature of aging is accumulation of damaged proteins this is what directly causes it.

 

And you saying that getting old "offers a shorter term advantage" -? What sort of advantage could it be?

 

 

I'm amazed at what lengths people are willing to go just to protect their long-held believes. Why the idea of programmed aging is to abhorrent to you guys?

 

Actually I'm not wedded to either the programmed or stochastic theories of aging. As I stated I've read both Josh and Aubrey's books. I'm well versed in both arguments. I am just being logical. We need to PROVE an adaptation is specifically aimed at faster aging, and not pleitrophic, i.e. an unintended side effect of another adaption. I do not know what that adaptation would be. But to prove programming you have to eliminate other linked adaptations.

[OP2040]

At this point I'm leaning toward the following scenario.

1. absolutely agree with Mitteldorf that group selection for stable populations is the evolutionary driver, however...

2. No proactive aging genes have been found to date, so...

3. Due to the "selection shadow" effect, it is most likely that youthful gene expression is tuned down, thus causing aging.

 

I still say development is very much a programmed affair, but it really doesn't matter to me whether the shutting down of gene expression that promotes aging be called programmed or something else. 

 

I think a lot of the evidence points to the above scenario. Much of the confusions comes from the "antagonistic hallmarks" like ROS, senescent cells and nutrient sensing.  I think the hallmarks paper has it right that these are merely secondary effects of the primary hallmarks.  So success with these will generate pretty good results and look like we are targeting damages.  But they don't really get at the core of what is causing aging, which are the primary hallmarks. 

 

Defending a theory means that you have to both explain the current evidence with it and there should be obvious implications that can point toward potential successful interventions.

 

The implications of the above hypothesis are that mimicking youthful gene expression would solve 99% of the aging problem.  The devil is always in the details.  In this case, the most important question is whether there is a hierarchy or if each system has a similar by separate path.  A good example of this is once again thymic involution.  Up-regulating FOXN1 does indeed regenerate the thymus.  But is there some higher level of gene expression that effects both FOXN1 and other genes at the same time for a more comprehensive rejuvenation.  In the past few years, there have been numerous reports of generating parts or whole of this or that organ with various gene expression interventions.  This is all very exciting, but something like OSKM reprogramming that potentially effects all these systems would be much better.

[xEva]

Actually I'm not wedded to either the programmed or stochastic theories of aging. As I stated I've read both Josh and Aubrey's books. I'm well versed in both arguments. I am just being logical. We need to PROVE an adaptation is specifically aimed at faster aging, and not pleitrophic, i.e. an unintended side effect of another adaption. I do not know what that adaptation would be. But to prove programming you have to eliminate other linked adaptations.

 

 

The direct adaptation is to the germ line. The stronger is the selective pressure, the faster must be the population turnover -- though I don't particularly like this term in the context of this discussion, because it somewhat displaces the focus from the paramount importance for the survival of a germ line to remain flexible and malleable. The only way to achieve this goal is to ensure the timely death of the individual.

 

To me, this requirement alone is a perfect argument for the programmed aging.

 

Also note that each species is characterized by a definite lifespan. and there is no other way to guarantee it except by extending the developmental program to include provisions for a timely demise of the individual. Aging is a good strategy, because its rate has directly impact on the lifespan.

 

 

And sorry, I have not read Josh book. Do you mind posting its thesis? I'm curious to know how he motivates the need for the 'population turnover'. one phrase

 

Though I started in the stochastic camp, for a few years already programmed aging has become a given to me -- so obvious it seems to my eyes. I even sorta forgot what were the arguments against it.

Edited by xEva, 12 December 2018 - 03:09 PM.

[QuestforLife]

The only way to achieve this goal is to ensure the timely death of the individual.

Not so, rapid breeding would supply the necessary individual variation in fast changing environments to weed out older, less adapted individuals.
 

Also note that each species is characterized by a definite lifespan. and there is no other way to guarantee it except by extending the developmental program to include provisions for a timely demise of the individual

Again, stochastic damage exceeding the rate of repair could also explain an exponential rise in mortality we observe in many species.

 

I should add that I personally believe repair mechanisms ARE turned down as we age, but that this is done as a tradeoff to protect the young from cancer.
 

[OP2040]

I should add that I personally believe repair mechanisms ARE turned down as we age, but that this is done as a tradeoff to protect the young from cancer.

 

 

This I'm definitely going to have to disagree with.  Although the study needs to be done, an intact immune system should provide adequate protection against cancer.  Alongside that, there are many counter-examples in nature to the aging-cancer trade-off.  Granted many of these examples do have specific mechanisms.  For example, elephants have a bunch of P53 genes.  Naked Mole Rats have contact inhibition provided by extra hyalauron.   Even so, it proves there is no inherent catch-22 that says aging mechanisms are necessary to prevent cancer. 

 

In a youthful state provided by the right genetic and epigenetic state, cellular senescence, immune system, ros and numerous other mechanisms would work just as well at keeping cancer in check.

 

I want to say that figuring out aging is just the start.  We will still need all the bio-engineering tools we are developing, like for example immunotherapy.  Because there will always be one-off instances and anomalies.  Our goal should shoot past curing aging to gain greater and greater rational control over the human body.  We want to own our own bodies via our own conscious choices and technology, whereas most of our current suffering is because we are subject to the whims of a body forged by the inhumane processes of evolution. 

[OP2040]

Here's a great chart based on some data to underline the point about cancer.

Immune system declines quite early as we already know, but cancer rises quite early too.

Attached Files

•  Capture.JPG   52.09KB   0 downloads

[QuestforLife]

This I'm definitely going to have to disagree with.  Although the study needs to be done, an intact immune system should provide adequate protection against cancer.  Alongside that, there are many counter-examples in nature to the aging-cancer trade-off.  Granted many of these examples do have specific mechanisms.  For example, elephants have a bunch of P53 genes.  Naked Mole Rats have contact inhibition provided by extra hyalauron.   Even so, it proves there is no inherent catch-22 that says aging mechanisms are necessary to prevent cancer. 

 

In a youthful state provided by the right genetic and epigenetic state, cellular senescence, immune system, ros and numerous other mechanisms would work just as well at keeping cancer in check.

 

I want to say that figuring out aging is just the start.  We will still need all the bio-engineering tools we are developing, like for example immunotherapy.  Because there will always be one-off instances and anomalies.  Our goal should shoot past curing aging to gain greater and greater rational control over the human body.  We want to own our own bodies via our own conscious choices and technology, whereas most of our current suffering is because we are subject to the whims of a body forged by the inhumane processes of evolution. 

 

I agree that immune decline is pivotal in the rise of cancer incidence with age. But granting the immune system cellular immortality might increase the cancer rate in the young, which evolution will do a great deal to avoid, including sacrificing the old.

 

All the other adaptations you mention, i.e. more copies of p53, can be evolved if required, but they take time and only occur if they offer survival benefit, such as in a large animal like an elephant.

 

That is not to say that we can't engineer these adaptions in ourselves.

Edited by QuestforLife, 12 December 2018 - 04:53 PM.

[OP2040]

Another interesting scientific observation that could inform this discussion is that of the proposed mortality plateau at old ages.  I've always been somewhat skeptical of this, but assuming it were true provides a whole different perspective on aging theory.  If mortality rates slow down toward zero after 80 and especially in the extreme old, what does that say?  Perhaps there are some positive aging genes at work in mid-life that fail at extreme old age thus allowing for declining mortality rate.  Perhaps having little to no immune system is better than the mid-life case where the little immune system you have is often working against you.  Would love to hear some thoughts on this phenomena.  Here's a quote from a study that fairly convincingly showed that it is a real phenomena and not just data driven:

 

 

Our findings further provide fundamental knowledge about the biodemography of human longevity. By using clean data from a single nation and straightforward estimation methods, we have shown that death rates, which increase exponentially up to about age 80, do decelerate thereafter and reach or closely approach a plateau after age 105. Thus, these well-estimated hazard curves share the qualitative pattern observed for extreme ages in widely differing species, regularities calling for common structural and evolutionary explanations.

 

[xEva]

Not so, rapid breeding would supply the necessary individual variation in fast changing environments to weed out older, less adapted individuals.
 

 

 

?? you say you are "being logical".  And yet you seem to be taking for granted that older individuals must be "less adapted".  This exposes your belief that "stochastic damage" occurs regardless, and can be only slowed down or accelerated. But this whole discussion is about whether diminished fitness with age is the result of the stochastic damage or a program.

 

Seems, for you it's both, with the stochastic part being a given and accelerated part, sorta optional.

 

 

Again, stochastic damage exceeding the rate of repair could also explain an exponential rise in mortality we observe in many species.

 

 

Exponential rise in mortality with age has nothing to do with a definite lifespan of each species.

 

Death is programmed through different strategies. Take closely related species of salmon. One dies immediately after spawning, the other makes it back to the ocean to reproduce again, and again. Closely related, they share the same habitat. What controls their life history if not particular to each species program? Apparently, both strategies are equally successful. 

 

 

I should add that I personally believe repair mechanisms ARE turned down as we age, but that this is done as a tradeoff to protect the young from cancer.
 

 

?? both the very old and the very young are the age groups most prone to cancer (though the types of cancers are different).

 

also, I don't understand what you mean by 'young'. In biology it's the individuals who have not yet reached sexual maturity.

 

As for the young in the human sense, they are young exactly because their repair mechanisms are still in good working order. When they start to falter is when the first signs of aging begin to appear and the fitness goes down.

 

But most importantly, how depression of repair mechanisms would protect from cancer -? I would expect the opposite.

 

 

PS

 and by the way, there are animals with negligible senescence whose fitness and fecundity increase with age. How come they are not subject of "stochastic damage"?

 

I guess what I'm driving at with this post is that there are different strategies and all of them are the result of the quirks of the program that dictates the life history of each species.

Edited by xEva, 12 December 2018 - 05:08 PM.

[QuestforLife]

?? you say you are "being logical". And yet you seem to be taking for granted that older individuals must be "less adapted". This exposes your belief that "stochastic damage" occurs regardless, and can be only slowed down or accelerated. But this whole discussion is about whether diminished fitness with age is the result of the stochastic damage or a program.

Seems, for you it's both, with the stochastic part being a given and accelerated part, sorta optional.



Exponential rise in mortality with age has nothing to do with a definite lifespan of each species.

Death is programmed through different strategies. Take closely related species of salmon. One dies immediately after spawning, the other makes it back to the ocean to reproduce again, and again. Closely related, they share the same habitat. What controls their life history if not particular to each species program? Apparently, both strategies are equally successful.



?? both the very old and the very young are the age groups most prone to cancer (though the types of cancers are different).

also, I don't understand what you mean by 'young'. In biology it's the individuals who have not yet reached sexual maturity.

As for the young in the human sense, they are young exactly because their repair mechanisms are still in good working order. When they start to falter is when the first signs of aging begin to appear and the fitness goes down.

But most importantly, how depression of repair mechanisms would protect from cancer -? I would expect the opposite.


PS
and by the way, there are animals with negligible senescence whose fitness and fecundity increase with age. How come they are not subject of "stochastic damage"?

I guess what I'm driving at with this post is that there are different strategies and all of them are the result of the quirks of the program that dictates the life history of each species.

You're so all over the place with this post it's hard for me to decide which element to respond to.

In terms of older individuals being less adapted to the environment, this is a given when the environment is changing rapidly.

As an example of reducing cellular repair with age, limiting telomerase puts a limit on cellular replication, which is the last line of defence against cancer. This doesn't effect the immunity of the young as by definition they've experienced less cell division. It does impact the old though, in a big way, screwing up all sorts of gene expression and the rate cells can turn over. Hence the drive to use telomerase therapy. Nature probably doesn't do this because it would not tolerate even a small increase in cancer in the young (i.e child bearing age), but we probably can do it with a one off telomere extending treatment and it would increase immunity without giving cancer the free pass limitless telomerase would provide.

Edited by QuestforLife, 12 December 2018 - 06:39 PM.

[xEva]

Another interesting scientific observation that could inform this discussion is that of the proposed mortality plateau at old ages.  I've always been somewhat skeptical of this, but assuming it were true provides a whole different perspective on aging theory.  If mortality rates slow down toward zero after 80 and especially in the extreme old, what does that say?  Perhaps there are some positive aging genes at work in mid-life that fail at extreme old age thus allowing for declining mortality rate.  Perhaps having little to no immune system is better than the mid-life case where the little immune system you have is often working against you.  Would love to hear some thoughts on this phenomena.  Here's a quote from a study that fairly convincingly showed that it is a real phenomena and not just data driven:

 

this was discussed here years ago. As I recall, unless there are new data sets, all examples are from lab animals or rare 'wild type' humans. With humans, it seems each such individual found a very stable lifestyle, which is more like a comfortable routine that lasts without change year in and year out. And the lab animals are rared in even more stable conditions.

 

My take on this is, such stability in the environment must promote the survival of individuals whose genome variations happen to be a good fit for the given parameters. I think their metabolism found an equilibrium and sorta keeps throttling on automatic -- until the first unexpected stressful event, which does not even have to be a major one. Anything out of the norm should push these outliers over the line.

 

With lab animals, it should be easy to demonstrate by suddenly starting to introduce changes in the conditions.

[xEva]

You're so all over the place with this post it's hard for me to decide which element to respond to.

In terms of older individuals being less adapted to the environment, this is a given when the environment is changing rapidly.

As an example of reducing cellular repair with age, limiting telomerase puts a limit on cellular replication, which is the last line of defence against cancer. This doesn't effect the immunity of the young as by definition they've experienced less cell division. It does impact the old though, in a big way, screwing up all sorts of gene expression and the rate cells can turn over. Hence the drive to use telomerase therapy. Nature probably doesn't do this because it would not tolerate even a small increase in cancer in the young (i.e child bearing age), but we probably can do it with a one off telomere extending treatment and it would increase immunity without giving cancer the free pass limitless telomerase would provide.

 

 

I was not all over the place. I was only responding to your incomprehensible to me statements. But I'm glad you explained what you meant.

 

Re your response,
Changes in the environment is stress. Why would the same stress  affect more adversely a chronologically older individual than a chronologically younger one? This makes sense only if stress responses in the older one are suppressed. 

 

And these changes in the environment do not seem to affect the animals with negligible senescence whose fitness increases with age. In other words, for these animals, older individuals will do better than the younger ones in the same stress conditions. How about that?

 

 

 

Re telomeres and cancer, that's an iffy subject, which hardly fits into this discussion. First, there is no good correlation between the average telomere  length and mortality, only with critically short telomeres. Second,  it's been long known that people born with telomerase defects in some tissues  tend to die early of cancer of the affected tissues.

 

This telomeres subject is similar to the subject of the senescent cells, meaning, are they the cause or the consequence of aging?

 

On the other hand, protein homeostasis is crucial for life. It all made of proteins! Once the quality control falters, everything, all systems, all tissues begin to suffer.

Edited by xEva, 12 December 2018 - 07:37 PM.

[QuestforLife]

I was not all over the place. I was only responding to your incomprehensible to me statements. But I'm glad you explained what you meant.

Re your response,
Changes in the environment is stress. Why would the same stress affect more adversely a chronologically older individual than a chronologically younger one? This makes sense only if stress responses in the older one are suppressed.

And these changes in the environment do not seem to affect the animals with negligible senescence whose fitness increases with age. In other words, for these animals, older individuals will do better than the younger ones in the same stress conditions. How about that?



Re telomeres and cancer, that's an iffy subject, which hardly fits into this discussion. First, there is no good correlation between the average telomere length and mortality, only with critically short telomeres. Second, it's been long known that people born with telomerase defects in some tissues tend to die early of cancer of the affected tissues.

This telomeres subject is similar to the subject of the senescent cells, meaning, are they the cause or the consequence of aging?

On the other hand, protein homeostasis is crucial for life. It all made of proteins! Once the quality control falters, everything, all systems, all tissues begin to suffer.

Thanks for responding, I didn't mean to be rude.

Regarding stress and the environment, even if older individuals do not have inhibited stress responses they can still be weeded out if the type of stress is not something they evolved to cope with. In the case of negligible senescence it will have evolved because conditions are unchanging and that animal has a very robust defence mechanism that can not be easily overcome, i.e. shell, flying, great intelligence.

I only mention telomeres because they are a great example of a trade-off between renewal capacity and cancer risk. I personally think they are a cause of aging but agree let's not open that up for discussion here.

[xEva]

Thanks for responding, I didn't mean to be rude.

Regarding stress and the environment, even if older individuals do not have inhibited stress responses they can still be weeded out if the type of stress is not something they evolved to cope with. In the case of negligible senescence it will have evolved because conditions are unchanging and that animal has a very robust defence mechanism that can not be easily overcome, i.e. shell, flying, great intelligence.

I only mention telomeres because they are a great example of a trade-off between renewal capacity and cancer risk. I personally think they are a cause of aging but agree let's not open that up for discussion here.

 

lol I'm sorry, I know I should have dropped this several posts ago, but I can't:

 

What makes a chronologically younger individual more adapted to a new set of conditions than the older one?

 

And related species, some with negligible senescence, others aging at a steady rate, live side by side in  overlapping habitats (turtles and sea birds), all sharing the same conditions.

 

I know, someone gotta stop this carousel. I'll play the adult here and chose to be the one

[QuestforLife]

What makes a chronologically younger individual more adapted to a new set of conditions than the older one?

Sexual selection is a random mix of genes so some offspring will be adapted and others won't to a given set of conditions. That's the main reason why clones spread fast but all die at once if conditions change.

And related species, some with negligible senescence, others aging at a steady rate, live side by side in overlapping habitats (turtles and sea birds), all sharing the same conditions.

And? Different species have different strategies. Rats live fast and die young on the ground. Squirrels live in trees so are hard to eat, therefore have had the chance to become much longer lived.

Edited by QuestforLife, 12 December 2018 - 10:54 PM.

[xEva]

Sexual selection is a random mix of genes so some offspring will be adapted and others won't to a given set of conditions. That's the main reason why clones spread fast but all die at once if conditions change.

And? Different species have different strategies. Rats live fast and die young on the ground. Squirrels live in trees so are hard to eat, therefore have had the chance to become much longer lived.

 

Ah yes! but this only underlines the importance of that mixing of the genes, iow, the flexibility and malleability of the germline.

 

What if there is a long spell of stable conditions? What if the individuals, and their offspring, with the best match to the current set of parameters overtake  the population?  What will happen to the genetic diversity of the germline then? And then what?

 

See, a timely death of individuals MUST be guaranteed. Otherwise, too much of a risk to take, no?

 

I think, Nature not only does not care about the best fit individuals (though they are always a pleasure to behold) -- but to the contrary, she would rather maintain a wide variety of individuals, many of whom, by definition, should be less adapted to the current conditions, in other words, be 'less fit'. Those betas, gammas and thetas who have to put up with the alphas are the custodians of the richness of the germline. They comprise Its treasure and its strength.

 

This has interesting implications for humans, who happen to be very adaptable species that colonized the whole planet (and are looking up into outer space).

 

A modern human has the advantage of being able to chose the environment in which he can thrive. I.e. he can move to another climate, adopt a diet and lifestyle that works best with what he got in the genetic lottery. Nice eh?

[QuestforLife]

Ah yes! but this only underlines the importance of that mixing of the genes, iow, the flexibility and malleability of the germline.
 
What if there is a long spell of stable conditions? What if the individuals, and their offspring, with the best match to the current set of parameters overtake  the population?  What will happen to the genetic diversity of the germline then? And then what?
 
See, a timely death of individuals MUST be guaranteed. Otherwise, too much of a risk to take, no?

Sexual selection will continue to cause mixing even in stable conditions. If a species has a low death rate from non-aging causes then it will naturally evolve a long life and slower aging (i.e. humans vs monkeys, say). The main downside of this, if you can call it that, is that - as you say - if conditions suddenly change, it will not adapt as quickly because of the longer life cycle. This in my view is why prey speicies have shorter lives than their predators.
 

Those betas, gammas and thetas who have to put up with the alphas are the custodians of the richness of the germline. They comprise Its treasure and its strength.
 
Nice eh?

Yes indeed, I agree. Although maybe cold comfort for the less-adapted members of a species that they represent genetic backup!

[OP2040]

Sexual selection is a random mix of genes so some offspring will be adapted and others won't to a given set of conditions. That's the main reason why clones spread fast but all die at once if conditions change.
And? Different species have different strategies. Rats live fast and die young on the ground. Squirrels live in trees so are hard to eat, therefore have had the chance to become much longer lived.

 

 

This makes sense to me.  Negligibly senescent animals often don't have much in common.  But one thing they might have in common is that they live in relatively safe environments as far as predation goes.  This evidence doesn't necessarily jive with the population boom and bust idea, but it would still be based on group selection.  The good news is that apparently various longevity genes are a thing that can and have been selected for many times in evolutionary history.  Or conversely, there could be death genes that are selected against.

 

I refer back to Michael Rose's work on fruit flies.  Fruit flies that live more than twice as long with not one deleterious consequence.  To me that says a lot about aging and death being a "functional" aspect of evolution.  I don't think we have all the answers, but we really need to toss out any theory that implies that aging is based on entropy or damage-alone.  It is very clear that, given the right evolutionary circumstances, living indefinitely is easy-peasy.

[QuestforLife]

This makes sense to me.  Negligibly senescent animals often don't have much in common.  But one thing they might have in common is that they live in relatively safe environments as far as predation goes.  This evidence doesn't necessarily jive with the population boom and bust idea, but it would still be based on group selection.  The good news is that apparently various longevity genes are a thing that can and have been selected for many times in evolutionary history.  Or conversely, there could be death genes that are selected against.

 

I refer back to Michael Rose's work on fruit flies.  Fruit flies that live more than twice as long with not one deleterious consequence.  To me that says a lot about aging and death being a "functional" aspect of evolution.  I don't think we have all the answers, but we really need to toss out any theory that implies that aging is based on entropy or damage-alone.  It is very clear that, given the right evolutionary circumstances, living indefinitely is easy-peasy.

 

So my view is yes to group selection and evolution of life-span as being niche specific. But no to selection of a specific aging pathways for their own sake.

 

I view the body as a system for resisting entropy as best it can, and given the chance, I.e. low death rate from external causes, it will get better at it through succeeding generations. Sometimes a species does have to select for faster growth and faster breeding, and this may also drive faster aging.

 

Michael Rose has does some great work with flies. And he has proven that fertility and aging can be de-coupled, as his flies are much longer lived AND produce more young. But they still lose out in competition will wild type flies. The conclusion? Life can select longer lives. But doing it without compromise takes time and (evolutionary) effort.