http ://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html

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I don’t see death during sepsis as “programmed”, I see it as a consequence of physiology doing something desperate under extremely desperate circumstances. Evolution has configured the immune system to minimize the sum of deaths due to not enough activation of the immune system (death from infection) and from too much activation (death from mitochondrial failure and multiple organ failure). When you have bacteria floating around in your blood stream, those are extremely desperate circumstances. If those bacteria form a biofilm, the chances of that infection killing you go up enormously. Nitric oxide prevents bacteria from forming a biofilm. During sepsis, the immune system makes gigantic amounts of nitric oxide. I think that NO is to prevent what ever microorganisms are causing the sepsis from forming a biofilm. It is “worth” a significant chance of death for the body to try and prevent biofilm formation because once a biofilm forms death becomes likely. Too much NO during high rate production of ATP from mitochondria will kill the mitochondria.

As I point out in my blog, that is the normal and absolutely necessary “off” switch for mitochondria, to prevent them from consuming O2 and substrate and generating lethal quantities of superoxide and H2O2. Mitochondria have essentially unlimited capacity to produce superoxide. They cannot be allowed to get into that state where even a few percent of mitochondria could consume more O2 and convert it into superoxide and H2O2 than all the rest of the body’s mitochondria combined.

The normal off mode of mitochondria protects organisms from mitochondrial failure 99.99% of the time. That sometimes it goes bad and organisms die from mitochondrial failure during sepsis is still a pretty good trade-off.

I think that all the other degenerative diseases mentioned are much the same, a bad physiological state brought about by normal physiology working at a bad setpoint or under physiological conditions where normal function produces pathology. For example I think that the degeneration of Alzheimer’s is due to ischemic preconditioning being continued for longer than is sustainable because the “off signal” for ischemic preconditioning isn’t sufficient to stop it. I think essentially all of the neurodegenerative diseases are a consequence of that.

From
Osteoarthritis: An example of phenoptosis through autonomic dysfunction? . Medical Hypotheses , Volume 67 , Issue 5 , Pages 1079 – 1085 A . Yun , P . Lee , J . Doux

“Phenoptosis, the programmed death of organisms akin to cellular apoptosis, constitutes a type of Darwinian selection that enhances inclusive fitness. It provides a means by which senescent and pre-senescent members can self-terminate if they have incurred sufficient cumulative stress such that their continued survival detracts from inclusive fitness. Sepsis, vascular disease, menopause, cancer, and aging all represent examples of phenoptosis at work.”

Here are two websites that discuss possible mechanisms for phenoptosis:

http://www.freeradicalscience.com/showabstract.php?pmid=10648966&redirect=yes&terms=phenoptosis

http://www3.interscience.wiley.com/journal/117890572/abstract?CRETRY=1&SRETRY=0

I can understand you not liking the term ‘programmed’, but it is commonly used in discussions of phenoptosis.

What is their evidence for such belief? You are implying teleology and then shifting the burden of evidence for such fictions onto your opposition. How would your position be falsifiable?

Give some real data (not merelya vague quote or link). Explain your position…..or cease in your lazy banter.

Bringing up vacous “what if” statements as if we were sipping cocoa by the stove is simply boring and it is difficult to engage in seriously, given that you are outright disputing scientific consensus. OK you dissent…good…any reason why?

I heard in an interview with the famous (infamous if you are a French swimmer) Michael Phelps that it was not uncommon for members of the team to comsume over 7000 calories in a day. I wonder how caloric intake is tied to an individuals metabolism, even if it is induced to be high.

Aubrey de Grey does not strike me as a kook. However, his ultimate goals, if met in an unexpectedly short period of time ( yes I know this is not likely) would surely lead to dramatic crises linked to overpopulation. Don’t get me wrong, I’m all Ponce de Leon on this one.

ps
nwtk: If your’e gonna get all pec on me, at least throw in some wit and humor.

Yes all eukaryotes have enzymes that degrade DNA. They have to because there are circumstances where DNA must be degraded. For example if one organism eats another organism the consumer must degrade the DNA of the consumee in order to utilize its nutrient value. During an infection, one strategy of stopping the infection is to degrade the DNA of the infecting organism. During autophagy, something which all eukaryotes exhibit, DNA sometimes must be degraded.

Do you have any evidence that there is programmed organism death? Any causes of death that are actively selected for and actively induced to happen under certain circumstances?

pec, each daughter cell descendent of an amoeba doesn’t survive. Those with degraded DNA survive less well, unless the changed DNA confers some advantageous trait.

But one cannot deny the existance of genes that induce cell death and you cannot deny the existnace of genes that induce DNA degradation, per say.

The idea of a program is simply an ad hoc assumption for which there is no evidence and which makes no predictions which could falsify it. At least none that I can think of. If you can think of a prediction that the idea of programmed DNA would predict then we can see if there is data to support or refute it.

As far as out and out DNA degradation is concerned, it is a true factor in DNA held not in living cells but when isolated or derived from a non-living source. DNA changes in living cells are usually not seen as degradation, but some would say so.

Just food for thought.

Even fragile sites are thought by some to be selected for in nature in many instances.

Again, aging is very complex but there is ample evidence to suggest a sort of pre-set limit to organism life span, effected by many, many different factors.

Hummingbirds that have evolved for higher altitudes have lower mutation rates. This is attributed to the reduced production of superoxide by their mitochondria as a secondary effect due to adaptation to high altitude.

http ://www.pnas.org/content/95/2/612

There are some disorders associated with DNA damage. Fragile X for example.

http ://hmg.oxfordjournals.org/cgi/content/full/14/suppl_2/R197

There just happen to be some sites in DNA molecules that don’t replicate as well and that these sites sometimes break during replication. Organisms with longer lifetimes have to have fewer of these sites because they experience early death if they don’t.

Just to clarify, I don’t think that “aging” is solely due to DNA degradation. I think that aging occurs simply because non-aging has not evolved because there hasn’t been any evolutionary pressure for it to happen. There are a great many different causes of death. Evolving solutions to all of them requires modification to a very large part of physiology.

Rate of aging and lifespan is an emergent property of organisms that have evolved. It isn’t something that is “added in”, or “programmed”, or that can be regulated independently of everything else. If you want to evolve organisms that don’t die from heart disease, you could select for them, but in selecting for fewer deaths due to heart disease you might increase deaths due to ischemic stroke because the heart doesn’t work as hard so the brain fails from lack of blood before the heart fails from overwork.

All of physiology is coupled and different aspects of it can’t be arbitrarily changed. Evolution has optimized physiology to a very large extent, but there are still individual variations which affect lifespan, but usually those effects only show up much later in life, during periods where “in the wild”, few humans reached.

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A dog, for example, will live 15 or so years, if it doesn’t get sick or hit by a car. It doesn’t matter how well you treat your dog, you know it will not live to 25. Why does a dog’s DNA degrade at that particular rate, if death is not programmed?

Certain parrots, on the other hand, have very long typical life spans, up to 100 years. Why would their DNA degrade so much more slowly than a dog’s DNA?

And why doesn’t the DNA of non-sexually reproducing organisms like amoebas degrade and wear out?