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Optimizing mitochondrial H2S for TFAM (and NMN/NAD+/SIRT-1)

h2s tfam mitochondria nad+ sirt-1 pqq resveratrol klotho ampk

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#1 Ukko

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Posted 18 February 2017 - 11:51 AM


So, fellow Longecitians, I think that this TFAM angle looks compelling:

 

http://www.nextbigfu...g-reversal.html

 

Thus, I was looking into what might optimize TFAM expression. Bumped into the usual suspects, like resveratrol, PQQ and so on.

 

https://www.ncbi.nlm...pubmed/23842073

 

https://www.ncbi.nlm...ubmed/19861415.

 

And, as to what might mess up things, again the usual culprits like a zinc deficiency, alcohol and so on,

 

https://www.ncbi.nlm...pubmed/26585415

 

https://www.ncbi.nlm...pubmed/19861415

 

Fair enough. But then I also bumped on an old "friend" that I have been bumping into regularly over the past 25 years or so. Sulphur. Particularly H2S gas. Which then of course implicates L-taurine and potentially NAC and lipoic acid. Once again.

 

https://www.ncbi.nlm...les/PMC3592015/

 

https://www.ncbi.nlm...pubmed/25758951

 

https://www.ncbi.nlm...les/PMC4630104/

 

https://www.ncbi.nlm...pubmed/22323590

 

https://www.ncbi.nlm...pubmed/23991749

 

http://www.sciencedi...043661816306314

 

https://www.ncbi.nlm...pubmed/24729176

 

http://www.sciencedi...014483512000851

 

https://www.ncbi.nlm...pubmed/10623586

 

While I recall some H2S discussion here, is there anyone having looked at H2S from the perspective of optimizing mitochondrial TFAM, Cyclic AMP, AMPK, NAD+, SIRT-1 and so on? What would be an actionable approach? Taurine? Vit B6 for CBS? NAC? For the CILTEP crowd...note that even LTP and NMDA feature in the last H2S link.

 

 


Edited by Ukko, 18 February 2017 - 11:55 AM.

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#2 Ukko

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Posted 18 February 2017 - 01:26 PM

More on H2S, NAC, mitochondria and the like.

 

https://www.ncbi.nlm...pubmed/12054683

 

https://www.ncbi.nlm...pubmed/23770272

 

https://www.ncbi.nlm...pubmed/26743493

 

https://www.ncbi.nlm...pubmed/25789157

 

https://www.ncbi.nlm...pubmed/18837652

 

https://www.ncbi.nlm...pubmed/27251093

 

https://www.ncbi.nlm...pubmed/25581647


Edited by Ukko, 18 February 2017 - 01:38 PM.


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#3 Ukko

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Posted 18 February 2017 - 02:26 PM

H2S looks very relevant:

 

https://www.ncbi.nlm...91098870002.jpg

 

Looks like cysteine might actually have to be restricted for optimal H2S ... perhaps there is a feedback mechanism there.

 

https://www.hsph.har...ion-identified/

 

While taurine, and maybe B6, look more like the way to go: 

 

https://www.research...ects_of_taurine

 

"Similar to resveratrol, H2S is likely a CR mimetic with potential antiaging functions mediated via SIRT1 activation."

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Edited by Ukko, 18 February 2017 - 02:45 PM.

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#4 adamh

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Posted 18 February 2017 - 07:26 PM

I seem to produce quite a bit of h2s, all this time I was improving the health of those around me and got no appreciation at all. Perhaps they can come up with a pill?


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#5 Ukko

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Posted 18 February 2017 - 07:42 PM

I seem to produce quite a bit of h2s, all this time I was improving the health of those around me and got no appreciation at all. Perhaps they can come up with a pill?

 

Watch this in between farting. H2S seems to explain CR/methionine restriction benefits. Am still looking into the cysteine angle. Finding conflicting info on it, but will revert once I have something to share. Do believe that NAC, Taurine and lipoic acid are beneficial.

 


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#6 ta5

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Posted 19 February 2017 - 02:03 AM

Not sure if you looked at garlic yet. This study touches on it (but somewhat negative about it, perhaps to put a more positive light on their novel drugs):

 

Pharmacol Res. 2016 Nov;113(Pt A):186-198. 
The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

 

Natural sources of H2S such as garlic were therefore, also tested with similar results: garlic extract protects against diabetic nephropathy, vasculopathy and cardiomyopathy [29], [30] and [31] and its active constituents were found to be diallyldisulfide (DADS) and diallyltrisulfide (DATS) [32], which are slower H2S donors than Na2S [33].

[...]

H2S supplementation using natural products may represent an alternative approach for long-term treatment. Garlic is the most commonly used sulfur-rich nutrient that can provide H2S using it either freshly or its extract as a dietary supplement. Allicin (diallyl thiosulfinate), the main source of H2S in garlic, decomposes to various sulfur-containing compounds in aqueous solutions including DADS and DATS [33], [53], [59]. DADS and DATS release H2S in a thiol-dependent manner and they may deplete the cellular glutathione pool [60], [61], [62]. While this chemical approach may help control the H2S release, the loss of glutathione increases the risk of oxidative damage in a pro-oxidant state like diabetes and H2S toxicity was also associated with it [63]. Interestingly, the opposite effect of DADS, an increase in the cellular glutathione level was also reported after prolonged treatment periods [64] that may be caused by H2S produced from the donors, since H2S itself increases the glutathione concentration [65]. However, if this is the case the elevated glutathione content should result in further H2S generation from thiol-dependent donors causing fluctuations in the H2S levels and making the dosing more complicated than with the HTB or ADT-OH-based donors. While the beneficial effects of garlic in diabetes models were confirmed by multiple studies [29], [30], [31], [66], garlic had no effect on endothelial function and oxidative stress in diabetic patients in a recent pilot trial and only little increase was detected in the glutathione level [67], which further support the difficulties with dosing of garlic-based dietary supplements.

 

 


Edited by ta5, 19 February 2017 - 02:05 AM.


#7 Harkijn

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Posted 27 February 2017 - 04:10 PM

' H2S seems to explain CR/methionine restriction benefits. Am still looking into the cysteine angle. Finding conflicting info on it, but will revert once I have something to share. Do believe that NAC, Taurine and lipoic acid are beneficial.'

 

Ukko, I am uncertain here, too. I hope you can find data that explain why garlic, onions and crucifers produce H2S, while conversely,  H2S is also produced by restricting the intake of sulfur containing amino acids. Can we have it both ways?

 


Edited by Harkijn, 27 February 2017 - 04:28 PM.


#8 Ukko

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Posted 02 March 2017 - 06:51 PM

' H2S seems to explain CR/methionine restriction benefits. Am still looking into the cysteine angle. Finding conflicting info on it, but will revert once I have something to share. Do believe that NAC, Taurine and lipoic acid are beneficial.'

 

Ukko, I am uncertain here, too. I hope you can find data that explain why garlic, onions and crucifers produce H2S, while conversely,  H2S is also produced by restricting the intake of sulfur containing amino acids. Can we have it both ways?

 

What I assume it is .... is some type of down regulation. The CBS and its downstream pathways towards Cysteine and Taurine are major producers of H2S. So there probably is a feedback mechanism of some type. Then again, Cysteine and Taurine are capable of releasing H2S at the cellular level. So what I suspect is that loading sulfur containing amino acids may reduce blood levels of H2S but increase the total body levels of H2S, particulary inside cells. Am looking into it. The thing being that the blood levels are of course easiest to monitor.
 



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#9 Harkijn

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Posted 02 March 2017 - 09:34 PM

 

' H2S seems to explain CR/methionine restriction benefits. Am still looking into the cysteine angle. Finding conflicting info on it, but will revert once I have something to share. Do believe that NAC, Taurine and lipoic acid are beneficial.'

 

Ukko, I am uncertain here, too. I hope you can find data that explain why garlic, onions and crucifers produce H2S, while conversely,  H2S is also produced by restricting the intake of sulfur containing amino acids. Can we have it both ways?

 

What I assume it is .... is some type of down regulation. The CBS and its downstream pathways towards Cysteine and Taurine are major producers of H2S. So there probably is a feedback mechanism of some type. Then again, Cysteine and Taurine are capable of releasing H2S at the cellular level. So what I suspect is that loading sulfur containing amino acids may reduce blood levels of H2S but increase the total body levels of H2S, particulary inside cells. Am looking into it. The thing being that the blood levels are of course easiest to monitor.
 

 

Thank you. While working my way  thhrough studies that are perhaps relevant, I really hope for your input.







Also tagged with one or more of these keywords: h2s, tfam, mitochondria, nad+, sirt-1, pqq, resveratrol, klotho, ampk

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