64 replies to this topic

[Kalliste]

How do we interpret these sort of studies that apparently seem to suggest that increasing ROS within the mitochondria increased longevity?  

 

http://www.scienceda...40508121245.htm

 

http://www.nbr.co.nz...ustry-die-56623

 

etc..?

 

Well asking if ROS is good or bad might be like asking if plastic is good or bad in a factory. Yes, no, maybe, depends on a complex web of contexts.

Consider this:

 

 

The process of metastasis is why malign cancers of all sorts turn out to be fatal in the end: their cells spread throughout the body to establish new tumors and outpace the ability of present treatments to keep up. The promise of the near future of cancer medicine is largely predicated on its ability to deal with metastasis. One approach is the use of targeted cell killing technologies that recognize cancer cells by their surface chemistry, capable of chasing down errant cells wherever they are in the process of spreading or building tumors. I think this is likely the type of treatment that will dominate the next generation of cancer treatments, as a range of different approaches to targeting are presently well advanced in the laboratory and clinical trials: immune therapies, simple nanomachines, engineered viruses, and so forth.

Another approach is to interfere with the process of metastasis in order to shut it down or at least suppress it, which would make many types of cancer more amenable to successful treatment with present day standards of surgery, radiotherapy, and chemotherapy. There hasn't been a great deal of success in suppressing metastasis in comparison to development of means to target cancer cells, but nonetheless a few approaches have been attempted. In the paper quoted below, researchers suggest that use of mitochondrially targeted antioxidants might be effective as a means of reducing metastasis to very low levels. If this bears out, it may attract more interest in the development of these compounds, which have been demonstrated to modestly extend life in mice as well as showing promise as treatments for a range of conditions.

Mitochondrial DNA damage is implicated in the progression of aging, and one theory is that this damage is caused by the generation of reactive oxygen species (ROS) within the mitochondria in the course of ordinary operation. So in theory life-long treatment with mitochondrially targeted antioxidants, carefully engineered compounds quite different from the antioxidants you can buy in a supplement store, will extend life by soaking up some of those ROS before they cause harm. As an approach to extending life this is poor in comparison to methods of mitochondrial damage repair, however. It can only slow the progression of aging somewhat, not turn back the clock.

Researchers at UCL identify a treatment that prevents tumor metastasis

Quote:
[Researchers have] succeeded in pinpointing a family of pharmaceutical compounds whose action prevents the appearance of tumor metastasis. The researchers achieved this tour de force by studying the mitochondria in tumor cells. These organelles are considered as the cells' power station. But when their functioning is altered, as [the] researchers observed in tumor cells, the mitochondria can promote cell migration, thus leading to the formation of metastasis.

[The researchers] examined the molecular mechanism responsible for the mitochondria's ability to promote metastasis. They succeeded in showing that, under certain conditions, the mitochondria produce more free radicals known as superoxide ions (O2.-). It is this overproduction of superoxide that leads to the formation of metastasis and, consequently, the growth of a tumor. Involved in other human pathologies such as Parkinson's and Alzheimer's disease, the production of superoxide by the mitochondria can be blocked by very specific antioxidants such as MitoTEMPO. Used in models of murine and human tumors, these compounds turned out to be very efficient at blocking the migration of tumor cells and preventing the spontaneous formation of human tumor metastasis in mice.

A Mitochondrial Switch Promotes Tumor Metastasis

Quote:
Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models.
 

https://www.fightagi... ... stasis.php

Quote:

Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD.

(Bolding added by me)

http://www.ncbi.nlm....pubmed/24665093

 

Edited by Cosmicalstorm, 02 August 2014 - 07:39 PM.

[niner]

How do we interpret these sort of studies that apparently seem to suggest that increasing ROS within the mitochondria increased longevity?  

 

http://www.scienceda...40508121245.htm

 

http://www.nbr.co.nz...ustry-die-56623

 

etc..?

 

Some of this sort of thing is hormesis.  Some of it is looking at the wrong kind of antioxidants.  Some of it is grandstanding academics claiming to have "turned the theory on its head"...  Some of it comes from a distorted picture of free radicals as "the" cause of aging.  They are a cause, but not the only cause.  An awful lot of this work is in worms, I notice.

[Turnbuckle]

How do we interpret these sort of studies that apparently seem to suggest that increasing ROS within the mitochondria increased longevity?  

 

http://www.scienceda...40508121245.htm

 

http://www.nbr.co.nz...ustry-die-56623

 

etc..?

 

People have seen these effects before with moderate drinking and low levels of radon exposure. For radon--

 

Exposure rates up to 100 WL [working level] tend to increase the median survival time of the exposed animals relative to the controls, while larger exposure rates decrease it. When modelling health effects from radiation, end points other than cancer should be considered too.

 

http://www.sciencedi...895717705001251

 

 

And it probably explains the popularity of the radon elixir that was popular early in the last century. A little was good, but too much could be very bad. As the WSJ put it, "The Radium Water Worked Fine Until His Jaw Came Off."

[george362a]

 

I also find this statement strange:
 

Since C60 is known to locate in the mitochondria and is believed to enhance its function (thereby creating more ROS), ...

improved mitochondrial function is supposed to generate less ROS. Old, dysfunctional mitochondria are known for their ROS reneration. To say that enhanced mitos function equates more ROS is very strange indeed. Was is a typo?

 

Mitochondria produce ROS in producing ATP, and both tend to decrease with age while the ratio stays the more or less the same.

In this study, ATP synthesis was significantly decreased in older subjects, supporting the concept that aging is associated with a decrease in mitochondrial function...In fact, the ROS/ATP production ratio, which reflects the number of ROS molecules generated during the production of one ATP molecule, were similar in younger and older individuals, indicating that differences in ROS production between groups are a function of the decreased ATP synthesis rate.

http://diabetes.diab.../60/8/2051.full

So if you boost the ATP production, you will likely also boost the ROS production.

In fact, reducing ROS without also reducing ATP has not yet been accomplished (as of 2010)--

Remarkably, we know very little about the specific mechanisms and sites of ROS production in mitochondria. There has been much recent interest, but there is controversy and disagreement, with different research groups favoring different sites (center 'o' in complex III, the Q-binding site in complex I, the flavin in complex I, or upstream dehydrogenases of the citric acid cycle). In this study we will identify the specific mitochondrial sites that produce ROS in cells.

There are currently no successful strategies to decrease ROS production at these sites without also compromising ATP production.

http://www.ellisonfo...synthesis-cells

So if you are using a protocol to increase ATP you will also likely increase ROS, and there's not much you can do about it except boost your mitochondria's primary anti-oxidant defenses, and that's why I take reduced glutathione and C, as noted in my previous post.

 

 

Might I suggest that a practice such as Earthing/grounding could supply free electrons which would help neutralize ROS and thus mitigate the effects of increased ROS production pursuant to C-60 therapy. Where increased ROS production would impair vascular function leading to ED, the concurrent use of a grounding pad or other device could be used to neutralize ROS and restore vascular (endothelial?) function addressing the problem of ED.

 

http://www.ncbi.nlm....les/PMC3265077/

 

http://www.ncbi.nlm....les/PMC4378297/

 

http://www.ncbi.nlm....pubmed/18047442

 

 

 

[Turnbuckle]

Might I suggest that a practice such as Earthing/grounding could supply free electrons which would help neutralize ROS and thus mitigate the effects of increased ROS production pursuant to C-60 therapy. Where increased ROS production would impair vascular function leading to ED, the concurrent use of a grounding pad or other device could be used to neutralize ROS and restore vascular (endothelial?) function addressing the problem of ED.

 

 

http://www.ncbi.nlm....les/PMC3265077/

 

http://www.ncbi.nlm....les/PMC4378297/

 

http://www.ncbi.nlm....pubmed/18047442

 

 

 

The research summarized here and in subsequent reports provides a basis for a number of earthing technologies that restore and maintain natural electrical contact between the human body and the earth throughout the day and night in situations where going barefoot on the earth is impractical. It is proposed that free or mobile electrons from the earth can resolve chronic inflammation by serving as natural antioxidants.

 

 

It's a basic principle of electrostatics that excess charge on a conductive body will be found on the outside surface. So even if not grounded and carrying a charge relative to ground, none of that will appear in the body, which is conductive. It's how a Faraday cage works. Now your first paper shows an effect on superficial wounds, which is possible as excess charge would appear there, and it is certainly true that healing of superficial wounds would improve overall heath. But what I don't get is why grounding would be preferable. If excess electrons quench free radicals and promote health, wouldn't a negative charge work better than grounding (zero charge)? If so, then the type of material used for the soles of shoes would be important. A shoe manufacturer interested in creating an electrically healthy shoe would examine the triboelectric series and pick a sole material that would produce a negative charge when in contact with common walking surfaces. Such shoes should be even healthier than going barefoot.

 

Polyurethane, a very common material for shoe soles, tends to charge strongly positive, but other rubbers, such as hypalon, butyl, viton and 

EDPM rubbers, charge negative. They are also very slightly conductive, which is what you want so that they will leak their acquired charge upward.

 

Another point is that excess charge will tend to accumulate in one's clothing (just as it accumulates in the hair and makes it stand out on dry days), so best to wear minimal clothes.