Oxidative stress: Less harmful than suspected?

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venkat raj

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Dec 5, 2011, 11:57:43 AM12/5/11
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Cathal Garvey

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Dec 5, 2011, 12:39:02 PM12/5/11
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Patrik

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Dec 6, 2011, 2:50:26 AM12/6/11
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Oxygen good.

Doogan

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Dec 6, 2011, 3:44:24 AM12/6/11
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As in Reactive Oxygen Species? ROS is bad. Not sure where you're
headed with this. Context please.

Cathal Garvey

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Dec 6, 2011, 10:57:29 AM12/6/11
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I would imagine that, like radioactivity, a little bit of ROS is good
for you; triggers upregulation of endogenous cell repair pathways, etc.

I'm sure there was supposed to be a link, probably a google reader link
by the look of the App in use.

Yet another reason to sigh at Mobile-App mediated communication, if you
ask me.


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Jeswin

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Dec 6, 2011, 11:02:04 AM12/6/11
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On Tue, Dec 6, 2011 at 10:57 AM, Cathal Garvey <cathal...@gmail.com> wrote:
> I would imagine that, like radioactivity, a little bit of ROS is good
> for you; triggers upregulation of endogenous cell repair pathways, etc.
>
> I'm sure there was supposed to be a link, probably a google reader link
> by the look of the App in use.
>
> Yet another reason to sigh at Mobile-App mediated communication, if you
> ask me.
>
wait, you guys didn't get the link??

http://www.physorg.com/news/2011-12-oxidative-stress.html

Gmail is being wonky recently.

Patrik

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Dec 6, 2011, 9:38:33 PM12/6/11
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Ah yes. These seem to be the primary sources:

http://www.dkfz.de/en/presse/pressemitteilungen/2011/dkfz-pm-11-65-Oxidative-stress-Less-harmful-than-suspected.php

http://www.cell.com/cell-metabolism/abstract/S1550-4131%2811%2900419-0

Highlights
- Genetically encoded redox probes visualize redox differences and
changes in vivo
- A chemical trapping strategy enables robust redox imaging in
dissected animals
- Physiological redox changes are redox couple, compartment, and
tissue specific
- Increased life span coincided with increased rather than decreased
tissue oxidation

Summary
The glutathione redox couple (GSH/GSSG) and hydrogen peroxide (H2O2)
are central to redox homeostasis and redox signaling, yet their
distribution within an organism is difficult to measure. Using
genetically encoded redox probes in Drosophila, we establish
quantitative in vivo mapping of the glutathione redox potential (EGSH)
and H2O2 in defined subcellular compartments (cytosol and
mitochondria) across the whole animal during development and aging. A
chemical strategy to trap the in vivo redox state of the transgenic
biosensor during specimen dissection and fixation expands the scope of
fluorescence redox imaging to include the deep tissues of the adult
fly. We find that development and aging are associated with redox
changes that are distinctly redox couple-, subcellular compartment-,
and tissue-specific. Midgut enterocytes are identified as prominent
sites of age-dependent cytosolic H2O2 accumulation. A longer life span
correlated with increased formation of oxidants in the gut, rather
than a decrease.


On Dec 6, 8:02 am, Jeswin <phillyj...@gmail.com> wrote:

Phil

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Dec 8, 2011, 4:48:31 PM12/8/11
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On Dec 6, 9:38 pm, Patrik <patr...@gmail.com> wrote:

> and tissue-specific. Midgut enterocytes are identified as prominent
> sites of age-dependent cytosolic H2O2 accumulation. A longer life span
> correlated with increased formation of oxidants in the gut, rather
> than a decrease.

Thanks for the redox redux. I don't think anyone had any
strong expectations about correlation between lifespan and
oxidants in the gut. ROS production within mitochondria
is the contentious issue. For decades, it was believed
by an increasing number of people that increased ROS in
mitochondria decreases lifespan. IIRC some recent studies refute
this.
Also, elimination of ROS in all mitochondria is fatal,
though this hasn't been published AFAIK.
Signalling via ROS may be essential to mitochondrial functioning.

Mega

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Dec 10, 2012, 9:34:37 AM12/10/12
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Hi,

As I was in an electronic store recently, at the end of the store there was a flask with pressurized oxygen.

Labelled: 

"
- healthy
- slows down cell aging
...

"


AFAIK, at least it won't slow the cellular aging process (and breathing in more oxygen won't make your physical state any better for sure, marathon runners rather do exercises in the mountains to have low oxygen to get more red blood cells).


What would be truely interesting, is to make a mammal live without oxygen and then compare the lifespan/ health in the same age    to another oxygen breathing one. But this won't be easy, by far not, I suspect... 

Mega

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Dec 10, 2012, 9:36:46 AM12/10/12
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(  Let alone that those 20 Liters of oxgen are neglible anyway ;) As only longtime exposure will count   )

Daniel C.

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Dec 10, 2012, 1:44:00 PM12/10/12
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On Mon, Dec 10, 2012 at 9:34 AM, Mega <masters...@gmail.com> wrote:
> What would be truely interesting, is to make a mammal live without oxygen
> and then compare the lifespan/ health in the same age to another oxygen
> breathing one. But this won't be easy, by far not, I suspect...

This experiment is currently being conducted all over the planet -
mammals that live at sea level get much more oxygen than those that
live in, say, the Himalayas. I only know of one mortality study where
altitude came up as a factor:
http://www.sciencedaily.com/releases/2011/01/110113131436.htm but I'd
be interested in learning more.

Also, if you literally meant without *any* oxygen, then that really
would be a challenge.

-Dan

Nathan McCorkle

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Dec 10, 2012, 2:19:57 PM12/10/12
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Let's find some mammals and kill de-oxygenate them till they live!



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Andreas Sturm

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Dec 10, 2012, 2:26:14 PM12/10/12
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Interesting!

Yeah, I imagine a metabolic pathway where a mammal just does anoxic metabolism. But the problem is, aerob metabolism gives you by far more energy. And, they would then produce acids, which they have to get rid of. The acids may have an effect on lifespan too. Maybe neutralizing the acids could work by producing bases in parallel? Or exporting the acids in a natural manner.



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Cathal Garvey

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Dec 10, 2012, 3:37:03 PM12/10/12
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Well, fermentation need not produce acid, but most fermentation methods
do. And yes, the difference is profound: with oxygen, each Glucose
molecule provides (IIRC) 32 units of ATP, whereas without oxygen you
only get.. 2? 4?
In fact, this is one of the things that makes Cancer so destructive;
most forms of cancer do not live by aerobic metabolism anymore, on
account of the "Warburg Effect":
https://en.wikipedia.org/wiki/Warburg_effect
..as a result, even a small tumour can devour vast amounts of blood
glucose compared to a normal body of tissue of the same size, especially
considering the high growth rate of cancerous tissues.

There is only one genus of "animal", as far as I'm aware, that is known
to live without oxygen:
https://en.wikipedia.org/wiki/Loricifera#In_anoxic_environment
..and they are quite small and live in sediments in the Med, so they
don't make a good example of a large, chordate animal that can survive
without oxygen.
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Andreas Sturm

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Dec 10, 2012, 3:50:09 PM12/10/12
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And yes, the difference is profound: with oxygen, each Glucose
molecule provides (IIRC) 32 units of ATP, whereas without oxygen you
only get.. 2? 4?

IIRC, 4 molecules ATP are produced, but two are used to activate the reaction. Making netto 2.

Wow, didn't know that about cancer.
Thanks for the link ;)








Cathal Garvey

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Dec 10, 2012, 4:03:27 PM12/10/12
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It's a fascinating effect, and one that surprisingly few cancer
researchers are aware of. In fact, almost nobody focuses on the Warburg
effect when seeking general purpose ways to target cancer, even though
it's one of the very, very few things that *most* cancers have in common.

It was looking at the Warburg effect that lead to the discovery that
dichloroacetate seems to cause cancer apoptosis; the researchers
screened a number of drugs known to activate mitochondrial pathways in
an attempt to reverse the Warburg effect, and lo-and-behold: DCA lead to
broad-spectrum induction of apoptosis against lots of cancer cell lines.

I wonder what would happen if you gave DCA to Loricifera? :P "SCIENCE!"
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