14 replies to this topic

[smithx]

Having read this paper, I stopped taking MitoQ (I have a few bottles left if anyone wants to make an offer):

 

The targeted anti‐oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

https://www.ncbi.nlm...les/PMC5880956/

 

Admittedly it was an in-vitro study, but I tend to err (sometimes) on the side of caution.

 

The same paper tested another mitochondria targeted anti-oxidant SS-31 and found it didn't cause any noticeable issues. On looking into SS-31 more, it seems possibly really great:

 

Mitochondrial targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice

https://www.ncbi.nlm...les/PMC3772966/

 

Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet

https://www.ncbi.nlm...les/PMC5621700/

 

SS-31 Provides Neuroprotection by Reversing Mitochondrial Dysfunction after Traumatic Brain Injury

https://www.ncbi.nlm...les/PMC6129854/

 

The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age

https://www.ncbi.nlm...les/PMC5392164/

 

Treatment with the mitochondrial‐targeted antioxidant peptide SS‐31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice

https://www.ncbi.nlm...les/PMC5847870/

 

The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes

https://www.ncbi.nlm...les/PMC6203778/

 

etc. etc.

 

Any thoughts? Any other such compounds worth considering? Possible group buy candidate?

 

More data on the compound https://newdrugappro....org/tag/ss-31/

 

 

 

 

[Daniel Cooper]

Is it commercially obtainable?

 

 

 

[smithx]

It appears to be patented and in a clinical trial currently. So it would be the kind of thing that could be synthesized for research or personal use, probably by someone like Genscript. One issue is that in at least some of the studies, it seems that this peptide is synthesized in what may be a fairly unusual solid phase method, so I'm not sure if it's unusually difficult to synthesize or something:

 

http://www.jbc.org/c...282/7/4634.full

 

 

SS31 (d-Arg-Dmt-Lys-Phe-NH₂; Dmt = 2′,6′-dimethyltyrosine) and SS20 (Phe-d-Arg-Phe-Lys-NH₂) were prepared by Dr. Peter W. Schiller (Clinical Research Institute of Montreal, Montreal, Quebec, Canada) using solid phase synthesis as described previously (24).

 

 

 

Is it commercially obtainable?

 

[JAYBEE00]

Hello,

 

Any more interest in this peptide?  Group buy?

 

Thanks.

[micro2000]

Likely will require injection to remain active.

[Turnbuckle]

Any thoughts? Any other such compounds worth considering?

 

 

Depends on what you want it to do. If you want it to increase the longevity of humans, I expect it would do the opposite, except for those who are very old. In the general case, ATP production goes into decline due to the buildup of defective mtDNA. So the treatment should involve getting rid of defective mtDNA, not in trying to squeeze out more ATP production from mitochondria.

[smithx]

One issue with aged mitochondria is that they produce more oxidants (ROS) which can travel through the cell and cause DNA breakages and damage other enzymes.

 

A mitochondrial-targeted antioxidant could neutralize those before they leave the mitochondria and therefore protect the rest of the cell. For example, a few years ago I proposed a mechanism by which muscle wasting (sarcopenia) could be at least partially caused by mitochondrial ROS damaging the rhyanodine receptors which maintain a correct ionic calcium balance and do become oxidized and less effective with age.

 

Reducing the accumulated damage caused by mitochondrial ROS could definitely increase healthspan if not lifespan, and reduce morbidity.

 

It is true that restoring mitochondria which function properly and don't produce more ROS would be preferable, but is there any evidence that we can do this?

 

 

Depends on what you want it to do. If you want it to increase the longevity of humans, I expect it would do the opposite, except for those who are very old. In the general case, ATP production goes into decline due to the buildup of defective mtDNA. So the treatment should involve getting rid of defective mtDNA, not in trying to squeeze out more ATP production from mitochondria.

 

[Turnbuckle]

 

It is true that restoring mitochondria which function properly and don't produce more ROS would be preferable, but is there any evidence that we can do this?

 

 

Cells do this automatically. It is only necessary to drive the natural process to extremes. I developed a protocol to treat myself, as the damage statins had done persisted for years, and it worked. This involves cycling fission/mitophagy with fusion/biogenesis -- https://www.longecit...ndpost&p=870740

Edited by Turnbuckle, 20 May 2019 - 08:18 PM.

[smithx]

It seems to be well established that aging mitochondria produce more ROS and less ATP. I have seen some of your posts about fission/mitophagy but am not sure that this would overcome the genetic damage to the mitochondrial genome which may be responsible for these problems. Are there any studies which confirm this?

 

Thanks for your comments.

 

 

Cells do this automatically. It is only necessary to drive the natural process to extremes. I developed a protocol to treat myself, as the damage statins had done persisted for years, and it worked. This involves cycling fission/mitophagy with fusion/biogenesis -- https://www.longecit...ndpost&p=870740

 

[Turnbuckle]

It seems to be well established that aging mitochondria produce more ROS and less ATP. I have seen some of your posts about fission/mitophagy but am not sure that this would overcome the genetic damage to the mitochondrial genome which may be responsible for these problems. Are there any studies which confirm this?

 

Thanks for your comments.

 

 

There is plenty of research. For instance--

 

Both mitochondrial fission and fusion seem to be required to maintain mitochondrial function. However, the mechanisms differ. Fission occurs probably to protect function by facilitating equal segregation of mitochondria into daughter cells during cell division and to improve distribution of mitochondria along microtubules tracks. In addition, fission may also help to isolate segments of damaged mitochondria, promoting their clearance 

https://www.hindawi....pd/2011/767230/

 

 

 

If even one of the 37 mtDNA genes is damaged and that mtDNA loop is alone in a mitochondrion, it's membrane potential (and ATP output) goes to zero (all 37 genes are essential). With no membrane potential, a protein called PINK1 begins to accumulate and recruits another protein called parkin, and that mitochondrion is thus marked for destruction in lysosomes. The process is well understood (if not well explained). From Wikipedia--https://en.wikipedia.../wiki/Mitophagy

 

Fission is important, as mtDNA loops cover for each other by supplying enzymes that are shared in a single mitochondrion. Raising NAD+/NADH fissions mitochondria and allows this process to occur. If you have only a little damage, one cycle might do you. But if you have a lot of damage, it may take many cycles. If a cell has 100% damaged mtDNA, then it cannot be salvaged short of a transplant of mtDNA.

Edited by Turnbuckle, 20 May 2019 - 09:51 PM.

[InquilineKea]

What about the paper made you stop taking MitoQ? Couldn't SS31 interfere with hormesis? (I heard mitochondrial DNA damage doesn't induce it as much as cytoplasmic damage BUT I still saw one paper that showed that it seemed to interfere)

[InquilineKea]

https://www.fightagi...-heart-failure/

 

https://www.facebook...737529173490980

 

it's not on canlab anymore

[QuestforLife]

Has anyone taken SS-31?

 

It seems to be available through various peptide suppliers now, so it might be worth a trial, either as a nasal spray, or more likely with bacteriostatic water and a subQ injection. It comes in 10,20 or 50 mg bottles. I've no idea of the dose but we could get some idea from mouse studies.  

[Advocatus Diaboli]

Elamipretide (SS-31) Failed to Meet Promise of Earlier Trial Results for Primary Mitochondrial Myopathy, Data Show

[QuestforLife]

okay thanks.