12 replies to this topic

[Logic]

I read Reason's post called Mitochondrially Targeted Antioxidant SS-31 Reverses Some Measures of Aging in Muscle.
http://www.longecity...ging-in-muscle/

Then did a search for 'SS-31 mitochondria'
There is a large body of research showing positive effects against Alzheimer's, high glucose, heart problems, the list goes on.
https://www.google.c...iw=1242&bih=499

My question is; is it worth looking at these papers to get a better idea of how C60oo works, or should one just synthesize SS-31 at home as Reason suggested?

[niner]

Very interesting! Look at these characteristics of SS-31 (from Reason's post linked above)

while SS-31 had no observable effect on young muscle.
These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial [ROS] emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment and eight days of SS-31 treatment led to increased whole animal endurance capacity.

Sounds familiar. The 'no observable effect on young muscle' is a little different for c60, since young people can see the fatigue resistance effect, which I suspect is because c60 may be better at catching ROS than SS-31. It might be the case that SS-31 is causing reduced ROS production, rather than detoxifying radicals directly. I think we should give SS-31 a hard look. Having done some organic synthesis, I'd have to say that neither SkQ1 nor SS-31 are kitchen chemistry problems, unless you have a hell of a kitchen.

Edited by niner, 26 May 2013 - 02:03 PM.

[Kevnzworld]

I was wondering the same thing.
It also made me think about how it relates to PQQ, another though different quinone.
" Most significantly, the study ( UCD, 2010 ) demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[8]"

[AdamI]

yeah it's very interesting. Seems to also have some kind of repairing mechanism going on, and not just ROS scavenger.
I'm up for it, anyone going to sell it:)?

[Logic]

Some studies on Alzheimer's and info on how SS-31 works:

Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease.

Mechanistically, the SS31 peptide targets the inner mitochondrial membrane, due to the electrostatic attraction between these cationic peptides (positive charge) and the highly anionic cardiolipin molecules (negative charge) of the inner mitochondrial membrane. Further, SS31 has a dimethyltyrosine residue, allowing SS31 to scavenge oxyradicals and inhibit linoleic acid and low-density lipoprotein oxidation. By reducing mitochondrial ROS, SS31 was able to prevent the opening of the mitochondrial permeability transition pore, prevent mitochondrial swelling and reduce cytochrome c release in response to a high Ca2+ overload.

http://hmg.oxfordjou...hmg.ddr381.full


These other studies are similar, by a similar group / some same people and are abstracts only:

Mitochondria-Targeted Antioxidant SS31 Prevents Amyloid Beta-Induced Mitochondrial Abnormalities and Synaptic Degeneration in Alzheimer’s Disease
http://www.mdpi.com/...-8247/5/10/1103

Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons.
http://www.ncbi.nlm....pubmed/20463406

[JohnD60]

I bought and read the study "Mitochondrial targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice". The results seemed less impressive after having read it, but I am hardly an expert. It is speculated that it somehow changes the glutathone redox status in the mito, and thus reduces H2O2 emission (which presumably is proxy for all reactive oxygen species emitted by mito complex II). But there is no discussion as to how long the reduced H2O2 emissions last in mice (and it would be problematic extrapolating that to humans).
There are custom peptide manufacturers that would probably make this 'for research purposes" for I believe about $500.
A problem I see is that injections were done 'intraperitoneally', roughly equivalent to intravenous for humans. Most peptides are injected subquetaneously, and thus easily administered, intravenous injection would present a significant road block for most people. On the other hand subq injections might work better as they would allow for a slower absorption of the peptide.

[Oki]

New SS-31 paper just came out. I had the opportunity to meet the professor running the lab last year and was really impressed with this research. Hit me up if you want the full text.

Aging Cell. 2013 May 20. doi: 10.1111/acel.12102. [Epub ahead of print]
Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice.

Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ.

Abstract

Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour. Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg kg^-1 of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and ³¹ P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle. These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial H₂ O₂ emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment, and eight days of SS-31 treatment led to increased whole-animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

[hav]

There's a slightly older compound called mitoquinone (MitoQ) which is similar in concept. Seems to be a form of ubuquinol (CoQ10) with lipid solubility modified for mitochondria targeting. I think its an SkQ1. I only mention it because its already showing up in anti-aging skin creams and available in 98% purity bulk form from Vosun Chemical in China.

Howard

[niner]

There's a slightly older compound called mitoquinone (MitoQ) which is similar in concept. Seems to be a form of ubuquinol (CoQ10) with lipid solubility modified for mitochondria targeting. I think its an SkQ1. I only mention it because its already showing up in anti-aging skin creams ...

MitoQ and SkQ1 are related mitochondrial-targeted antioxidants. Both use a triphenylphosphonium cation as the mitochondrial targeting agent, and are both quinones. It's a bit of a concern to see it in skin cream, since it can act as a pro-oxidant in the presence of atmospheric oxygen.

[Roshelle]

SS-31 is in FDA clinical trials under the name Bendavia, it definitely seems to have some interesting repair abilities. Skulachev and his team have applied for trials of skq1 recently, both are to be taken orally. I've seen skq1 on open cures and I can't even imagine making that myself I have no idea abut Bendavia/SS-31 but I suspect they will be available online in time for research purposes only of course.

[niner]

Thanks, Roshelle, I didn't have a clue about Bendavia. Here is a paper about Bendavia in IR injury:

J Am Heart Assoc. 2012 Jun;1(3):e001644. doi: 10.1161/JAHA.112.001644. Epub 2012 Jun 22.
Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide.
Kloner RA, Hale SL, Dai W, Gorman RC, Shuto T, Koomalsingh KJ, Gorman JH 3rd, Sloan RC, Frasier CR, Watson CA, Bostian PA, Kypson AP, Brown DA.

Heart Institute of Good Samaritan Hospital, University of Southern California, Los Angeles (R.A.K., S.H., W.D.) ; Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles (R.A.K., W.D.).

BACKGROUND:

Manifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the "no-reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically.
METHODS AND RESULTS:

We investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models. Postischemic administration of Bendavia reduced infarct size in an in vivo sheep model by 15% (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S staining and was significantly smaller in the Bendavia group for any given ischemic risk area than in the control group (P=0.0085). Myocardial uptake of Bendavia was ≈25% per minute, and uptake remained consistent throughout reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by Bendavia in any of the models studied. Isolated myocytes exposed to hypoxia/reoxygenation showed improved survival when treated with Bendavia. This protection appeared to be mediated by lowered reactive oxygen species-mediated cell death during reoxygenation, associated with sustainment of mitochondrial membrane potential in Bendavia-treated myocytes.
CONCLUSIONS:

Postischemic administration of Bendavia protected against reperfusion injury in several distinct models of injury. These data suggest that Bendavia is a mitochondria-targeted therapy that reduces reperfusion injury by maintaining mitochondrial energetics and suppressing cellular reactive oxygen species levels.

PMID: 23130143 PMCID: PMC3487333 Free PMC Article

Considering that the results they saw were all obtained when the mitochondrially targeted peptide was given AFTER coronary artery occlusion, imagine the protective effect of having c60-oo on board BEFORE a heart attack or stroke. I think your odds of recovery would be dramatically improved. I suspect that c60 is a way better antioxidant than TRP.

[Nemo888]

Anyone know where to get some? Stealth Peptides is the real deal and is doing proper clinical trials.

 

I wonder is a combination of this and thymosin beta 4 could put into remission neuronal degenerative conditions like  Alzheimers or Gelsolin amyloidosis.

Edited by Nemo888, 11 July 2014 - 11:34 AM.

[pone11]

 

There's a slightly older compound called mitoquinone (MitoQ) which is similar in concept. Seems to be a form of ubuquinol (CoQ10) with lipid solubility modified for mitochondria targeting. I think its an SkQ1. I only mention it because its already showing up in anti-aging skin creams ...

MitoQ and SkQ1 are related mitochondrial-targeted antioxidants. Both use a triphenylphosphonium cation as the mitochondrial targeting agent, and are both quinones. It's a bit of a concern to see it in skin cream, since it can act as a pro-oxidant in the presence of atmospheric oxygen.

 

 

It is worth mentioning that there are reports of MitoQ and SkQ1 impairing mitochondrial energetics.   SS-31 does NOT have this effect, so that is a very significant differentiator.

 

Fink BD, Herlein JA, Yorek MA, Fenner AM, Kerns RJ, Sivitz WI: Bioenergetic effects of mitochondrial-targeted coenzyme Q analogs in endothelial cells. J Pharmacol Exp Ther 2012, 342:709–719.

 

Reily C, Mitchell T, Chacko BK, Benavides G, Murphy MP, Darley-Usmar V: Mitochondrially targeted compounds and their impact on cellular bioenergetics. Redox Biol 2013, 1:86–93. 193. Gane EJ, Weilert F, Orr DW, Keogh GF, Gibso