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Longevity Mutants Unfit In Natural Environment


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#1 Michael

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Posted 03 February 2007 - 07:49 PM


All:

While laypeople and non-biogerontologist biologists often subscribe to the idea that we are 'programmed to age and die' (usually as a means to clear out the old to free up resources for the young, and/or to facilitate evolutioin by increasing teh turnover of the generations), almost no gerontologists do: the idea is actually logically incoherent granted the basic logic of natural selection. Instead, almost noall biogerontologists subscribe to some version of the idea that aging is the result of stochastic molecular damage taht is only partially prevented or repaired because to invest the resources into creating maintenance mechanisms powerful enough to obliterate such effects would be a waste, because natural selection selects organisms that leave behind the most viable progeny. Thus, evolution tendds to select for maintenance systems that retard aging ENOUGH to let them live out a relatively long life relative to what can be expected if they aren't killed by starvation, predation, exposure, etc, but not DRAMATICALLY more, and to instedad invest the same resources in either things related to reproduction (fertility, attractiveness, etc) or things related to surviving those other, grossly environmental threats (warmer fur, sharper claws, etc). Such ideas can be grouped under the "disposable soma theory," and mechanisms include thhe lack of selective pressure against mutations whose ill effects are felt only late in life -- most dramatically, inthe case of "antagonistic pleiotropy," where a trait is selected because it has effects that are beneficial for fitness, but that cause negative consequences that are not normally felt in the wild, but are seen when the organism is shielded from teh natural environment's hazards and are allowed to actually age (eg, growth hormone and sex steroids and reproductive and other cancers).

An apparent challenge to this has been raised by studies in C elegans (tiny roundworms) and other model organisms that have mutations that dramatically slow the rate of their agign, seemingly at no cost to fitness. However, studies have shown that this is often the result of the animals not being subjected to the rigors of a natural environment, and that when they have to compete udner more natural conditions, they rapidly lose out to their wild-type cousins. Examples:

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Author: mikalra
04/12/06 - REPOST "No Fitness Tradeoff for Longevity?" WAS Re: Prospects for aging medicine http://lists.milepos...ociety&P=R18040
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Author: mikalra
04/12/06 - Longevity Mutants Lose Darwinian Fitness: More Evidence
http://lists.milepos...ociety&P=R18356
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User name: seemysig@googlemail.com
Password: simplepassword

CR certainly seems to be another, less extreme example (because its detriments are more obvious). CR APPEARS to be a program that shifts resources away from reproduction and puts them into maintenance, allowing the organism to survive a famine intact, to breed another day. But clearly, if *perpetuated* in the wild, the CRed mouse's low fertility, body size, and temperature would make it a total loser if it had the CR phenotype when others didn't.

Now, here's another one:

Biol Lett. 2005 Jun 22;1(2):247-9.
The longevity of Caenorhabditis elegans in soil.
* Van Voorhies WA, Fuchs J, Thomas S.

... An important issue when interpreting results from these studies [of anti-aging interventions in C. elegans] is the similarity of the observed C. elegans We found that ... C. elegans mutants that live twice as long as wild-type worms in laboratory conditions typically die sooner than wild-type worms in a natural soil. ...

This should give pause to those looking to intervene in aging by pharmaceutically exploiting these pathways (a standard strategy of the "gerontologist's school" of anti-aging biomedicine), and again reinforce the benefits of allowing metabolism to remain in its normal state, but cleaning up the ensuing damage directly, at the molecular level, iteratively pushing the level of damage beneath the threshold of pathology (the "engineer's school" of anti-aging biomedicine).

PMID: 17148178 [PubMed - indexed for MEDLINE]

-Michael
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#2 manofsan

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Posted 04 February 2007 - 02:56 AM

But when we talk about "losing out in the fitness competition" we have to remember that we as humans are no longer a hunter-gatherer species living that same original lifestyle. I for one am willing to trade off a little fitness in exchange for enough longevity.

Likewise, adrenaline and aggression instincts that may have once been helpful in clawing that piece of meat away from your rival may now be misplaced in our modern civilized society, and could get you arrested. Not everything that we still carry with us from the past is optimally useful for us today.

Come to think of it, it may be useful for us to catalog our lifestyle differences that have emerged between then and now, for the purpose of seeing what we can throw away and sacrificially trade off in our pursuit for greater longevity. We shouldn't automatically assume that longevity will be achieved without tradeoffs, and it may then help us to know what genetic baggage we can throw away or barter in exchange for longevity gains.

Do we still need an appendix, for example? I thought we don't use it anymore.
Do we really still need body hair? We wear clothes now. Isn't it a waste of metabolic effort and resources?
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#3 John Schloendorn

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Posted 04 February 2007 - 07:12 PM

Is it known how well the longevity mutants compete with wild-types in protected environments?
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#4 apocalypse

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Posted 05 February 2007 - 02:52 AM

But when we talk about "losing out in the fitness competition" we have to remember that we as humans are no longer a hunter-gatherer species living that same original lifestyle. I for one am willing to trade off a little fitness in exchange for enough longevity.

Likewise, adrenaline and aggression instincts that may have once been helpful in clawing that piece of meat away from your rival may now be misplaced in our modern civilized society, and could get you arrested. Not everything that we still carry with us from the past is optimally useful for us today.

Come to think of it, it may be useful for us to catalog our lifestyle differences that have emerged between then and now, for the purpose of seeing what we can throw away and sacrificially trade off in our pursuit for greater longevity. We shouldn't automatically assume that longevity will be achieved without tradeoffs, and it may then help us to know what genetic baggage we can throw away or barter in exchange for longevity gains.

Do we still need an appendix, for example? I thought we don't use it anymore.
Do we really still need body hair? We wear clothes now. Isn't it a waste of metabolic effort and resources?

Once we tap into ever greater energy sources, efficiency won't matter as much. With sufficient energy we can actually do some pretty nice stuff. I'd say tolerance and acceptance is what we'll need to avoid conflict. Some people are just gonna turn into something that seems sick and uncontrollable, yet we must try and see how such things fit in with the rest of our world view, and try to understand their point of view.

The exchange of information is the basis of democracy, the more varied and exotic the information, the greater the required tolerance, but also the greater the freedom and peace that is achieved. Prohibiting or limiting information exchange can steer us to, shall we say, undesirable locations... like police states, tyranical governments and the like. Open source, entrance into the public domain must be protected from the law makers actions.

S class hackers can avoid low lvl cops/fbi agents and trick them into harassing little girls and grandmas making them look like villains... it would be nice if the law makers accepted the public's decisions and actions, if they tolerated and made the law for the people and by the people, things change and they should understand that.
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#5 caston

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Posted 05 February 2007 - 03:05 AM

Is it known how well the longevity mutants compete with wild-types in protected environments?


I suppose we'll just have to try to get along with them.

Do we really still need body hair? We wear clothes now. Isn't it a waste of metabolic effort and resources?


Well although we probably have just as many strands of hair as say an ape for example it has been getting a lot thinner. I doubt we would ever lose body hair entirely.
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#6 John Schloendorn

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Posted 05 February 2007 - 04:01 AM

I suppose we'll just have to try to get along with them.

Haha fair enough Caston.
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#7 caston

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Posted 05 February 2007 - 07:23 AM

All:
Instead, almost noall biogerontologists subscribe to some version of the idea that aging is the result of stochastic molecular damage taht is only partially prevented or repaired because to invest the resources into creating maintenance mechanisms powerful enough to obliterate such effects would be a waste, because natural selection selects organisms that leave behind the most viable progeny.


What about the theory that less than perfect DNA repair is also the basis for evolutionary transformations also known as mutations?
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#8 apocalypse

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Posted 05 February 2007 - 07:30 AM

All:
Instead, almost noall biogerontologists subscribe to some version of the idea that aging is the result of stochastic molecular damage taht is only partially prevented or repaired because to invest the resources into creating maintenance mechanisms powerful enough to obliterate such effects would be a waste, because natural selection selects organisms that leave behind the most viable progeny.


What about the theory that less than perfect DNA repair is also the basis for evolutionary transformations also known as mutations?


Well, recombination can do just as good a job, I think, look at the immune system's varied antigen repertoire... and it's somehow connected to the nervous system... the most complex object in the universe, connected to a system with the ability to edit dna, the molecules of life itself. Woah?!? I've always wondered if that could be exploited somehow.
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#9 caston

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Posted 05 February 2007 - 07:45 AM

apocalypse: Not completely sure what you mean but what I was suggesting is that evolutionary transformations would be moot if we had perfect DNA repair. Perhaps in biology there is a trade off between allowing some mutations but repairing most of the DNA so that the organism still has a chance to produce off-spring? In high radiation enivornments DNA repair is improved to allow survival of the organism.

Complex organisms don't get to be complex organisms if their ancestors immortality is put before natural transformation. Ever wondered why we breath oxygen if it causes so much DNA damage? And why does NASA consider oxygen a requirement for the evolution of complex life?

Would lifeforms be much simpler if the ozone layer blocked significantly more UV light?

Would lifeforms be both simpler and longer lived if they used Homologous recombination instead of Nonhomologous DNA end joining?

http://www.gnxp.com/...ves/003722.html

Edited by caston, 05 February 2007 - 08:16 AM.

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#10 apocalypse

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Posted 06 February 2007 - 09:40 AM

apocalypse: Not completely sure what you mean but what I was suggesting is that evolutionary transformations would be moot if we had perfect DNA repair. Perhaps in biology there is a trade off between allowing some mutations but repairing most of the DNA so that the organism still has a chance to produce off-spring? In high radiation enivornments DNA repair is improved to allow survival of the organism.

Complex organisms don't get to be complex organisms if  their ancestors immortality is put before natural transformation. Ever wondered why we breath oxygen if it causes so much DNA damage? And why does NASA consider oxygen a requirement for the evolution of complex life?

Would lifeforms be much simpler if the ozone layer blocked significantly more UV light?

Would lifeforms be both simpler and longer lived if they used Homologous recombination instead of Nonhomologous DNA end joining?

http://www.gnxp.com/...ves/003722.html


Well, besides some key tricks to help reassemble heavily broken up dna strands, from what I've heard, even radiation resistant heavy weights(e.g. radiodurans) practically reuse most of the same dna repair mechanics and proteins other less resistant organisms use.(Of course, this does not mean that such repair mechanisms and methods are utilized to the max in the various tissues. )

Given the existence of mobile elements, and the fact that somehow this sort of repair seems enough for extremophiles(btw, some researchers have hinted that mars' experiments suggest the possibility of high hydrogen peroxide content cells being present there... again if this is later proven, it will show the unbelievable power of cellular design.), it may somehow be good enough for all practical purposes.
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#11 caston

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Posted 06 February 2007 - 04:52 PM

thanks apocalypse,

I hope to learn a lot more about DNA repair.

I believe they have found extremophiles that can exist without oxygen? They are of interest because similar life may be able to survive on Mars. I assume extremophiles exist for extreme heat, extreme cold, extreme radiation and environments with little water or oxygen?
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#12 caston

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Posted 08 February 2007 - 02:42 PM

I assume this article is evidence against my thesis?:
http://www.pubmedcen...i?artid=1205397

I think it dismisses it to easily.

How does genetic determination of offspring in sexual reproduction work again?

What is the probably that a DNA error (as well as the mechanism that caused or failed to repair it) gets passed on and is actually advantageous?

Or should I just ask is that probably > 0 ?

Edited by caston, 08 February 2007 - 03:40 PM.

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#13 apocalypse

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Posted 11 February 2007 - 10:50 PM

I assume this article is evidence against my thesis?:
http://www.pubmedcen...i?artid=1205397

I think it dismisses it to easily.

How does genetic determination of offspring in sexual reproduction work again?

What is the probably that a DNA error (as well as the mechanism that caused or failed to repair it) gets passed on and is actually advantageous?

Or should I just ask is that probably > 0 ?


Probabilities are relative, we'd need more knowledge to truly be 100% certain of what we're saying. But evidence indicates it should be, as with everything in science this is just what we've learned till now(and can always be open to question, in the future.), some mutations will be beneficial while others will not be. Our knowledge, as far as I can tell, indicates most of the mutations/errors are detrimental, but the few that are beneficial are spread exponentially ever faster, thanks to the benefits they confer to the self-replicating entities or cells on which they fall/occur.
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