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Death Spiral Research

death life cycle genetic senescence

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#1 Lazarus Long

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Posted 29 July 2016 - 06:53 PM


Sorry I haven't been around for a while but I've been very busy. However this article today caught my attention.  If this research is validated then perhaps we should re-examine the theories around the idea of a biological clock.  However, seeing the life cycle in phases is not mutually exclusive to the basic idea of senescence due to cumulative mutation.

 

What this research does do is link back to Dawkin's selfish gene in the sense that when we cease to be fecund we also seem to accelerate the aging process and initiate at some point the "death spiral". More research is needed to integrate the various theories of aging.

 

https://www.yahoo.co...178.html?ref=gs

 

Death Spiral: 4th Phase of Life May Signal the End Is Near
 
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July 29, 2016
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There may be common signs in organisms that signal a spiral toward death.
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Biologists separate life into three phases: development, aging and late life. But a growing body of research now suggests that there is a fourth phase immediately preceding death that scientists have dubbed the "death spiral."

Although most of the "death spiral" research has focused on fruit flies, scientists think these studies can offer valuable insight into the last stage of human life as well.

"We believe this is part of the process of, basically, genetically programmed death," Laurence Mueller, chair of the Department of Ecology and Evolutionary Biology at the University of California, Irvine, said in an interview with Live Science. [What Are Your Odds of Dying From …]

Expiring fruit flies

Over the past decade, several studies of fruit flies have suggested this spiral toward death can be seen in the drop in reproductive rate (fecundity), according to a review of this research by Mueller and his colleagues, published earlier this year in the journal Biogerontology. For instance, researchers reporting in 2015 in The Journals of Gerontologyfound that the first day a female fly laid zero eggs was a significant predictor of death: Indicators of fecundity started to decline about 10 days before young female fruit flies laid zero eggs. The researchers think that whatever leads to the flies' deaths also affects their ability to reproduce in their final days.

In the new review, Mueller said that the timing of this decline matches another previous estimate of the death spiral's duration. Relative to the average life span of a fruit fly, 10 days could be as much as a third of a fly's life, Mueller said. Research from 2002 on Mediterranean fruit flies, called medflies, found that 97 percent of males began lying upside down about 16 days prior to death. In relative terms, this potential indicator of a death spiral is also approximately equal to the timing of the fecundity decline in the fruit flies. [The Science of Death: 10 Tales from the Crypt & Beyond]

In another study, scientists observed fruit flies, nematodes and zebrafish, to see if their intestines exhibited increased leakiness before death. The researchers tested this leakiness, called permeability, by feeding food dye to each animal. If permeability increased, that dye would leak out into the animal's body, and its body would change color — blue in the flies and fish, and fluorescent green in the nematodes. The research, published online March 22 in the journal Scientific Reports, concluded that this intestinal leakiness was a marker of death in all three species.

A human death spiral?

The hope is that death-spiral research in fruit flies and other organisms could someday tell scientists more about the decline of humans prior to death. [8 Tips for Healthy Aging]

In their review paper, Mueller and his colleagues cited a study from 2008 published in the journal Proceedings of the National Academy of Sciencesas evidence that people may experience the death spiral as well. In that study, researchers analyzed data collected on the physical and cognitive abilities of 2,262 Danish people, ages 92 to 100, from 1998 to 2005. They found that the physical and cognitive scores of individuals who died within the first two years of the study were significantly lower than the scores of those who were still alive in 2005. The assessments included measures of grip strength, ability to complete daily activities (such as using the toilet and eating) and exams that helped evaluate cognitive impairment.

Basically, Mueller said, a death spiral in people could be the reason we often see a distinct increase in disability just before a person dies. Humans are challenging study subjects for both ethical and biological reasons, but looking at the death spiral in other organisms could give scientists a window into how this works in humans, the researchers said.

According to Mueller, the next step in this research might be to selectively breed the flies to create groups that experience death spirals of different durations.

"Once you create populations that are genetically different in that way, you can ask, 'What genes were changed in order to reduce the length of the death spiral?'" Mueller said. Using that knowledge, researchers could look at the human genome for similar genetic markers; humans are genetically similar to fruit flies, Mueller noted. According to yourgenome.com, a website of the Wellcome Genome Campus, 75 percent of disease-causing genes in humans are also present in fruit flies.

 

Mueller said the research isn't about stopping or even delaying death. Rather, he sees it as a way to improve people's quality of life when they are reaching the end and potentially save immense amounts of money in end-of-life health care.

"Even if we don't affect when you die, we'd like to make you fully functional up to the day you die," he said.

Original article on Live Science.

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#2 Never_Ending

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Posted 06 August 2016 - 08:53 PM

What they state does not seem to be sufficient to show indication of it being "Programmed".

 

A CASCADE effect is not the same as a clocked program.  Damage can trigger a cascade effect because once some organism is deteriorated to a certain extent there is enough disruption so that things aren't able to maintain themselves and they just start falling apart.

 

This isn't to say damage is the only factor(I'm not ruling out other factors), but their findings don't seem to be a sufficient indicator of their conclusion.

 

As a side note things like "death spiral" sound like attractive terms for researchers to use. It might give the impression that something new has been found... all they really showed was that when an animal is at a certain state(which would be strongly correlated with age if you took an average) an animal begins to fall apart and this could of course lead to death.


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#3 Lazarus Long

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Posted 07 August 2016 - 04:32 PM

First off I agree that a cascade effect per-se is not the same thing as a "clocked program", and may be more analogous to a system crash in an overclocked system.

 

I post articles like this to encourage thought and out of the box thinking, not to proselytize a POV of my own.

 

However, the idea of a multifaceted time keeping methodology for organisms is not unrealistic.  First off, we already have a diurnal metabolism that depends on a sleep cycle, a cycle that does influence aging when not adequately met.  Second, we do age through specific growth phases, pre then post natal, infancy, prepubescent, pubescent, early adult (fecund & formative), mid adult caregiver (more of a steady-state phase that is about social development and rearing young) and then the early through late senescent phase that reflects the wide range of cumulative and sometimes irreversible cellular damage.

 

What the authors called the fourth phase (from my previous words you can surmise that I didn't accept the 3 phase argument to begin with) is something that scientists have observed for some time and wondered if it was actually programmed genetically or was some kind of consequence of total systemic failure (death).  What I find interesting is that the authors are asserting the genetic argument and that the spiral begins "prior" to physical death.  Also, that it may be accelerating physical decline and the rate of senescence.

 

I have witnessed this effect in my parents and the aging parents and long term ill of others.  However, that is both true and anecdotal.  It neither validates the proposal nor explains it. Why would such a death spiral exist if is it genetically programmed?  What kind of a selection advantage would such a death spiral provide?  And since it evolved for all if not most lifeforms, what is the mechanism and role of its activation?  It should be possible to be observed in both simple as well as complex species.

 

I offer the suggestion that this might be seen as a composting switch, a genetic program designed to initiate decomposition of the body in order to provide a more sustaining environmental ecology. Consider it a kind of environmental feedback loop. Biological recycling of basic materials to create a more sustaining environment for offspring in a generic sense.

 

Anyway, if a sequence of genetic switches can be identified and influenced this could do a number of things toward "buying time".  One, as the authors suggest it might provide a way to improve life during the latter phase of senescence, it might be switched off to improve the efficacy of treatment and allow more precise targeting of specific ailments, and third, it might allow for a more prolonged period prior to the initiation of cryo to make that technology more feasible.

 

These are just 3 ideas off the top of my head but I imagine there are more reasons that understanding and confirming this research might be both practical and of deeper theoretical importance.



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#4 Never_Ending

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Posted 08 August 2016 - 01:46 AM

Yeah my concerns on it was basically directed at the research article itself. I'm sure we all have views somewhat related but not limited to the articles in reference.

 

 About what you mentioned of there possibly being a time keeping mechanism for later life aging, I feel that if there was a mechanism like that it would be likely activated due to a difference in state.  What I mean is somehow the genetics would have to determine that this organism is considerably less fit than one of a newer generation. Or else there would be no benefit in favoring a newer generation if it was pretty much the same just more recent. As people perhaps we might think that everyone should have a fair amount of time therefore favoring the next generation might seem appealing. However evolution wouldn't be driven by those concepts. On the other hand it would make sense evolutionarily if the organism was deteriorated to a certain extent that it would be better to clear the way for genetically similar but less deteriorated versions. So really there is only a small distinction in my view, it's that imo there's still a type of deterioration that is doing the triggering.


Edited by Never_Ending, 08 August 2016 - 01:53 AM.


#5 niner

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Posted 08 August 2016 - 02:43 AM

The "death spiral" phenomenon certainly appears to be real; we see it in all aging animals.  However, accumulating damage in a complex machine will show the exact same effect, so it's not at all evidence for a "programmed" explanation.  The most we could say is that a programmed scheme might look something like that.   A late-life programmed decline is a complicated thing for evolution to generate and maintain, so we would need to have a good explanation for the evolutionary pressure that would cause it.  In a world where creatures routinely die from predation, infection, violence, or starvation long before they age to death, I'm at a loss as to what the evolutionary pressure would be.  Frankly, it doesn't look like it exists. 



#6 Never_Ending

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Posted 08 August 2016 - 12:54 PM

In a world where creatures routinely die from predation, infection, violence, or starvation long before they age to death, I'm at a loss as to what the evolutionary pressure would be.

I agree and also imagine if such an active mechanism exists then a genetic mutation in that mechanism is very likely to happen and  there would be people that show a significantly different old age profile without deterioration.

It might even be easier to break an active mechanism(with help of genetics) than to invigorate an overall deteriorating organism.  So it's not at all due to optimism to refute the "programmed" concept,  because both possibilities seem to be potentially changeable.



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#7 Lazarus Long

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Posted 12 August 2016 - 07:28 PM

I agree and also imagine if such an active mechanism exists then a genetic mutation in that mechanism is very likely to happen and  there would be people that show a significantly different old age profile without deterioration.

 

Be careful, you're assuming the mutation would express in a directly opposite manner.  There is no necessity for that.  It could easily express as early onset Alzheimer's or Progeria.

 

Also folks be very careful not to anthropomorphize the Natural Selection process, nor assume it is directed from gene side as opposed to the environmental pressure on genes. A successful mutation in one environment could spell disaster in another, and a failed mutation in one generation could provide an advantage after a major climactic change.  The environment drives evolution even though how species have evolved has also from time to time influenced the environment. We are not even the first species to influence the environment.

 

Also I would ask everyone to consider why there are genes that specifically turn on after death?

 

 

Thanatotranscriptome: genes actively expressed after organismal death

http://biorxiv.org/c...16/06/11/058305

 

 

Hundreds of genes seen sparking to life two days after death

The discovery that many genes are still working up to 48 hours after death has implications for organ transplants, forensics and our very definition of death

https://www.newscien...ys-after-death/

 

 

So let us return to the question: What kind of selection pressure has granted an advantage to switching genes on after death?







Also tagged with one or more of these keywords: death, life cycle, genetic senescence

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