30 replies to this topic

[tunt01]

This recent article piqued my interest:

Hydrogen Sulfide: The Next Anti-Aging Agent?

http://www.scienceda...30129121945.htm

The evidence is mounting, they note, that hydrogen sulfide slows aging by inhibiting free-radical reactions, by activating SIRT1, an enzyme believed to be a regulator of lifespan, and probably through its interactions with a gene, klotho, which appears to have its own market basket of anti-aging activity.

This got me back to recalling prior threads, conversations and topical discussion of H2S


Could Hydrogen Sulfide Hold The Key To A Long Life?

http://www.scienceda...71203190614.htm

http://www.longecity...-life-of-worms/

researchers found, to their surprise, that nematodes that were raised in a carefully controlled atmosphere with low concentrations of H2S (50 parts per million in room air) did not hibernate. Instead, their metabolism and reproductive activity remained normal, their life span increased and they became more tolerant to heat than untreated worms.
The H2S-exposed worms lived eight times longer than untreated worms...


Roth hypothesizes that H2S, a chemical normally produced in humans and animals, may help regulate body temperature and metabolic activity. Hydrogen sulfide is similar to oxygen at the molecular level because it binds at many of the same proteins. As a result, H2S competes for and interferes with the body's ability to use oxygen for energy production -- a process within the cell's power-generating machinery called oxidative phosphorylation.
The inhibition of this function, in turn, is what Roth and colleagues believe causes organisms such as mice to shut down metabolically and enter a hibernation-like state pending re-exposure to normal room air, after which they quickly regain normal function and metabolic activity with no long-term negative effects.

We know that garlic upregulates Hydrogen Sulfide production. Garlic is known to be heart healthy and act like an ACE-inhibitor.

http://www.pnas.org/...nt/104/46/17977

The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H₂S), an endogenous cardioprotective vascular cell signaling molecule. This H₂S production, measured in real time by a novel polarographic H₂S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H₂S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RS_nH), a key intermediate during the formation of H₂S. Organic polysulfides (R-S_n-R′; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RS_nH and H₂S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H₂S. The vasoactivity of garlic compounds is synchronous with H₂S production, and their potency to mediate relaxation increases with H₂S yield, strongly supporting our hypothesis that H₂S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H₂S can be used to standardize garlic dietary supplements.

Issues:

1. Does anyone have any thoughts on the above? Should we just chalk it up to a SIRT1 activator and examine other SIRT1 activating compounds just as readily as H2S?

2. Various garlic extracts and supplements exist. Some do not contain Allicin (see chart toward bottom containing principal organosulfur compounds: http://lpi.oregonsta...emicals/garlic/). Which garlic supplement should we target?

3. Should we instead be targeting N-Acetylecysteine (NAC) and/or other compounds that stimulate H2S instead? (at least it doesn't smell like garlic...)


Thanks.

Edited by prophets, 31 January 2013 - 08:01 AM.

[xEva]

That's interesting and I'm waiting what responses you'll get.

In the meantime, re this:

3. Are there other supplements which stimulate H2S that are not garlic (and do not SMELL like garlic!)?

Horseradish -- not a supplement, and is smelly, in a more H2S way than even garlic, lol. Makes a fantastic condiment. I don't think you can get H2S without the smell. S is always smelly-?

[tunt01]

Horseradish -- not a supplement, and is smelly, in a more H2S way than even garlic, lol. Makes a fantastic condiment. I don't think you can get H2S without the smell. S is always smelly-?

thx

I think NAC might be another option. But IDK enough about NAC to know whether or not it has the same fundamental effects as a SIRT1 activator, etc.

I bookmarked a few links/articles, emailed a medical researcher, and am going to comeback to the subject matter this weekend.

Edited by prophets, 31 January 2013 - 08:09 AM.

[tunt01]

Notes/links to self to review later:

http://ajpregu.physi...2/R297.full.pdf

http://www.jci.org/articles/view/41376

http://www.lmreview....ne-up-part-III/

[YOLF]

Definitely interesting. Awaiting responses and I love the taste of garlic! I eat that stuff like a vampire hunter! Like several grams/day of the powder spice stuff and sometimes much more if I'm cooking or eating other foods that have the stuff in it. Not sure I understand how it's good for me though.. Thought hydrogen sulfide was a poison, but I guess there could just be an optimal level. Can there be any benefit from H2S in the air?

[Elus]

Wow, I had this hypothesis years ago when I watched hydrogen sulfide being used to induce suspended animation!
Link:http://www.youtube.com/watch?v=uVAaZVz9pDs
http://www.youtube.com/watch?v=uVAaZVz9pDs

Here's an e-mail exchange between myself and Michael Rae from 2010.

7/20/10

My name is Michael Rae; I'm one of Dr. de Grey's research assistants, and coauthor of his recent book, "Ending Aging:"

http://www.amazon.co...e/dp/0312367074

(This is the new, paperback edition, which has an Afterword covering some of the advances in SENS science that were made after the publication of the hardcover).

With all of his duties in research, promoting engineering-based biotechnologies to arrest and reverse biological aging, and the promotion the book, Dr. de Grey has for some time been unable to keep up with most of his correspondence; when he received your email, he asked me to send his apologies, and answer your question as best I can. My apologies for the long delay in getting back to you! I often run a couple of days behind, but I have just discovered that the system I had been using to keep mail to SENS Foundation was not also segregating messages passed on directly to me to Dr. de Grey, so I am really, truly behind at the moment on those -- my apologies.

You wrote:

I had an idea based on the TED talk by Mark Roth about suspended
animation ().

He used hydrogen sulfide to induce suspended animation in mammals.
This suspended animation reduces basal metabolic rate to an
incredible degree. Could we use the same concept/chemical to slow
metabolism of mice for a few hours a day, each day, and thus reduce
the damage caused by metabolism? Could this slow aging? Could we
apply it to humans?

I know it's a pretty far out idea, but I would be interested to hear
your opinion.

Well, there's a couple of things, there. Many hibernating animals do seem to live unusually long compared to similar-sized mammals, so it's not crazy to think that a drug that induced hibernation might slow aging. It's not totally clear that the reason for this is directly linked to the act of hibernating itself, however: in general, animals that are better-protected from environmental causes of death (such as predation or freezing to death) tend to evolve, in turn, bodies that are more resistant to age-related degeneration, since it is more likely that, absent an early death from those external causes, it will be able to leave more viable offspring behind if it is kept functional for a little longer.

This is why, for instance, bats have evolved longer lifespans than similar-sized mice, with whom they are otherwise close genetic cousins: not because flight itself slows down the aging process, but because being able to fly is a great way to avoid being eaten by most things, so evolution invests in building a slower-living body. Similarly, an animal that can spend the cold months safely buried away, not subject to freezing to death or being eaten while out scrounging for food, might evolve a slower-aging body for reasons that aren't directly caused by the act of hibernation.

But supposing that it worked, I really don't think it would help us much. This proposal is one of many rexamples of what Dr. de Grey has termed the "gerontological" approach to developing interventions against aging, under which, one first tries to tease apart the metabolic origins of the cellular and molecular damage that underlies aging, and then modulate those pathways in youth to make them less damaging, so that less damage is caused and we accumulate less over time, leading to slower aging.

There are two reasons to think that this intuitive-sounding approach –- which is, actually, basis for several interventions that do slow aging in experimental animals -- will not lead to effective anti-aging interventions in humans. The first is that this approach requires us to tease apart these pathways to the nth degree, so that we can manipulate them in ways to benefit us. Unfortunately, our TOTAL KNOWLEDGE (and not just a wall chart, which by its nature must simplify if it's to be reasonably comprehensive) about metabolism is "woefully incomplete," and is likely to remain so for a very, very long time. A system as complex as a human body by its nature is a very complex, built as finely-regulated, interlocking homeostatic systems, built out on each other like multidimensional echo chambers, and tinkering with one aspect inevitably ripples in unexpected ways through the entire system.

But precisely because metabolism IS so incredibly complexly interrelated, perturbing the body's normal metabolic regulation puts one at risk of unanticipated consequences: our bodies are designed to operate as finely-balanced homeostatic systems, and interfering with the basic pathways underlying our normal functionality (especially in our current state of relative ignorance about the body's complex metabolic processes) inevitably causes undesired side-effects.

An additional, general feature of such approaches is that because they rely on reducing the *rate* at which biomolecules become damaged by the metabolic processes contributing to aging, they can nly *retard* the rate of aging, not arrest or reverse it; this limits their effectiveness, particularly in people older than middle age, in whom significant aging damage has already accumulated.

the other thing, of course, is that to the extent that you slowed aging, you'd effectively lose the time you gained, since the 2 hours a day you spent in slow aging mode, you wouldn't be able to be awake to enjoy -- and you'd be aging at a slowed rate, rather than not aging at all, while aging at a normal rate for the other 22 hours a day.

Instead, the "engineering" approach, pioneered by Dr. de Grey, notes that what distinguishes young bodies (which have the same metabolic pathways, but are normally healthy except in congenital disease) from old one is damage to its molecular and cellular structures. By removing, repairing, replacing, or rendering harmless the inert molecular and cellular damage whose accumulation underlies the slide into frailty that is aging, we can return those essential biomolecules to their youthful fidelity, creating a body that is structurally and functionally young, its metabolic derangements corrected as downstream consequences of the intrinsic order of the youthful body. With this return to normal functionality at every level will come restored youth, health, vigor, and vitality.

The basic outlines of this are presented on the SENS Foundation website here:

Hi Michael,

Thank you for your reply! In your response, you said that effective
anti-aging interventions can happen only if we address the damage
which builds up over time to cause pathology. I agree with this. Any
other approach will simply delay the inevitable accumulation of
garbage within cells that results in pathology and death.

However, let's imagine for a moment that this technology is a bit out
of reach within our lifetimes. Perhaps we get unlucky (I DEARLY HOPE
NOT!)... What could we do to extend our lifespan to the point where
this technology is feasible? Well, hydrogensulfide could be one
solution, couldn't it? Dr. de Grey often talks about the initial
anti-aging interventions which will results in 30 or so years of
extra life and that those breakthroughs will allow us to live long
enough to see the onset of refinements of those anti-aging
interventions. If those initial interventions prove to be difficult
to obtain, we could use hydrogensulfide to suspend ourselves further
into the future where those first interventions are a reality.

Right. Well, a lot of people are pursuing cryonic suspension for exactly this reason. There's a balance there, of course: compared to cryonic suspension, H2S-based deep hibernation would be very easy to test in progressively larger and more closely-related species and then (if everything seems OK) translate and implement in humans, and we could then relatively quickly and easily determine whether it's working or not, and wouldn't have a terribly hard time continuing to monitor patients.

However, as I said, it's not clear whether H2S-induced hibernation would slow aging appreciably or at all (the obvious answer to this could be, of course, to test it), and it seems to me that even a pretty profound deceleration is unlikely to be of much help in practice. The dilemma is this: who do you put into hibernation, and when? Remember, to whatever degree hibernation may reduce the *rate* at which biomolecules become damaged by the metabolic processes contributing to aging, they can nly *retard* the rate of aging, not arrest or reverse it. So if you put a person who is already very close to age-related death into hibernation, because the therapies are still years away, their *existing* burden of aging is so high that slowing down the rate of aging by even, say, 20% when they have, say, a 5-y life expectancy means that they might gain an extra year, which is unlikely (though not impossible!) to be the deal-breaker for reaching escape velocity; further souring this is that older, more damaged bodies are less likely to be able to make the metabolic shift into hibernation (as you see with CR and with natural hibernation), and to survive the hibernating state (an experimental therapy probably requiring some form of life support in a species not adapted to it to avoid eg. ulcerating bed wounds, and starvation), the nonzero toxicity of H2S, and then the rigors of the first, crude generation of SENS therapies themselves. On the other hand, who is going to consent to being put in hibernation while still young, healthy, and vigorous? (And that assumes continuous hibernation; a couple of hours a day, even at a 20% slower aging rate, is equivalent to a 3.3% slower aging, and whatever the process of inducing and removing the suspension process 'costs' the body physically and the patient in time and hassle).

Full cryonic suspension in principle eliminates this by essentially reducing molecular decay to zero. In practice, however, we know that we can't achieve that yet -- microcracking during vitrification, and imperfect implementation of the procedure -- and it's not clear when we'd be able to safely reverse it even if it were perfectly implemented.

It seems to me that the resources required to make any of this work would be better spent fueled directly into accelerating the development of the therapies that will save (in principle) *everyone's* lives.

Edited by Elus, 01 February 2013 - 04:28 AM.

[Adaptogen]

I would be willing to bet that I eat more garlic than anyone on this forum

[xEva]

Can there be any benefit from H2S in the air?

lol yes, the benefit would be to make people avoid your house and leave you alone.

on the other hand, that's the air in old sulfur springs spas like Rimini.

Edited by xEva, 01 February 2013 - 06:59 AM.

[tunt01]

Can there be any benefit from H2S in the air?

go to the original post. read the 2nd quoted block text.

[joelcairo]

Nematodes raised in 50 ppm H2S lived 8 times longer than controls. Wow. But all I know is what I read in Wikipedia, and H2S apparently has quite toxic effects in humans at that level. Also the threshold for humans being able to detect its odor is only .00047 ppm. Wow again. This is 100,000 times that level, probably quite smelly.

[joelcairo]

...A more complete quotation from the article cited above:

"The H2S-exposed worms lived eight times longer than untreated worms when moved from normal room air (22 C or 70 F) to a high-temperature environment (35 degrees Celsius, or 95 F)." Still interesting, but it seems more like it aids in stress adaptation.

[Bron]

I would be willing to bet that I eat more garlic than anyone on this forum

How much do you eat? I eat between 10-20 cloves a day. Crushed and set for 10 minutes.

[Adaptogen]

My garlic consumption falls within that range. Sometimes i worry I am eating too much though, considering I also supplement with pretty large doses of a handful of other anticoagulants: fish oil, ginger, turmeric, and piracetam

[YOLF]

Wow that's alot of garlic! I only eat several grams in the powdered spice form each day.

[Bron]

My garlic consumption falls within that range. Sometimes i worry I am eating too much though, considering I also supplement with pretty large doses of a handful of other anticoagulants: fish oil, ginger, turmeric, and piracetam

Hmm. I also take turmeric and fish oil. Sometimes I eat ginger but it is not a daily thing.

Guess I should look into this as well. I will send you a pm or something if I find anything or ever find something to be wrong with me.

I did just have blood work done... I could have sworn I had my fibrogen levels checked but I don't see it.

My platelet count does seem to be on the low side, although my doctor didn't say anything. And he is a good doctor, MD/PhD in internal medicine from Georgetown. 141 thousand/uL.

I don't bruise easily at all, and I also don't bleed much. In fact I just had a striker needle test done after exercise. The needle was a ridiculously oversized 14 gauge. Bleeding stopped quickly with just a slight bit of pressure.

Anything else I should be on the lookout for? And thanks for bringing this up, the last thing I want to do is ruin my health.

One thing I was worried about is if the excessive allicin would wreck my healthy gut flora. Doesn't seem to though, although besides inaccurate stool testing, I am not sure how I would check.

I am very regular, however that doesn't mean everything is OK. I do also drink kefir everyday and have a diet loaded with fruit and vegetable.

I have an appointment with a gastroenterologist this tuesday, I will see what he has to say and let you know.

[Adaptogen]

Thanks I look forward to hearing back from you. I don't think there is any reason for concern, at least I hope not. I only mention it because I have seen a few people bring up the risk of cerebral hemorrhaging when combining a few anticoagulants. Vitamin K seems to be a smart supplement choice as it increases coagulation, but I am not currently taking any. I just try and eat a good amount of kale/mustard greens a couple times a week.

http://www.longecity...ic-stroke-risk/
and continued discussion http://www.longecity...-with-fish-oil/

[1kgcoffee]

Fresh garlic juice - yes the juice of garlic - makes me feel incredible. But oh god, the smell comes out of every pore. So offensive...

[bobz1lla]

Fresh garlic juice - yes the juice of garlic - makes me feel incredible. But oh god, the smell comes out of every pore. So offensive...

Pretty sure fresh garlic(raw) has been shown to cause the inside of your intestines to become inflamed. The Allicin content I believe...

[Bron]

Fresh garlic juice - yes the juice of garlic - makes me feel incredible. But oh god, the smell comes out of every pore. So offensive...

Pretty sure fresh garlic(raw) has been shown to cause the inside of your intestines to become inflamed. The Allicin content I believe...

I have searched. I have only read conjecture, no evidence. Not saying it is not out there, but I have looked for it and haven't found a thing.

All the conjecture has me concerned. My diet also includes a lot of capsaicin, another substance touted to do the same damage as allicin.

I will eventually get an upper gastrointestinal endoscopy. Then I think my anecdotal evidence will be able to either quell or greatly exacerbate fears, considered I am literally the poster child for allicin and capsaicin consumption...

Edited by Bron, 15 March 2013 - 11:40 PM.

[Bron]

Thanks I look forward to hearing back from you. I don't think there is any reason for concern, at least I hope not. I only mention it because I have seen a few people bring up the risk of cerebral hemorrhaging when combining a few anticoagulants. Vitamin K seems to be a smart supplement choice as it increases coagulation, but I am not currently taking any. I just try and eat a good amount of kale/mustard greens a couple times a week.

http://www.longecity...-stroke-risk/
and continued discussion http://www.longecity...-with-fish-oil/

Thanks. Add another to the list of concerns. I will read through these.

I do take K, as it is part of my multi, and I get large doses through my diet. I am off the charts on my cron meter...

Also I love kale Kale chips are my favorite snack:

http://nynaturals.my...ions/kale-chips


My GI doesn't seem to be concerned with my garlic nor my capsaicin intake fyi.

[spermidine]

I would be willing to bet that I eat more garlic than anyone on this forum

How much do you eat? I eat between 10-20 cloves a day. Crushed and set for 10 minutes.

why would you be doing that ? both of you guys. are you young and healthy ? why would a young person megadose on something like that ? i guess people keep saying balance is the key yet the moment you assume something is actually good, you megadose on it. *shakes head*

[Adaptogen]

I am addicted

[Bron]

I would be willing to bet that I eat more garlic than anyone on this forum

How much do you eat? I eat between 10-20 cloves a day. Crushed and set for 10 minutes.

why would you be doing that ? both of you guys. are you young and healthy ? why would a young person megadose on something like that ? i guess people keep saying balance is the key yet the moment you assume something is actually good, you megadose on it. *shakes head*

It's garlic. I don't "megadose" it. It is part of my diet. Same with capsaicin. I don't do extracts or supplements with either.

Until I find even a shred of evidence that either is harmful, I will continue to do so.

Edited by Bron, 16 March 2013 - 03:16 PM.

[spermidine]

I am addicted

addicted how ? what is the part that addicts you ?

I would be willing to bet that I eat more garlic than anyone on this forum

How much do you eat? I eat between 10-20 cloves a day. Crushed and set for 10 minutes.

why would you be doing that ? both of you guys. are you young and healthy ? why would a young person megadose on something like that ? i guess people keep saying balance is the key yet the moment you assume something is actually good, you megadose on it. *shakes head*

It's garlic. I don't "megadose" it. It is part of my diet. Same with capsaicin. I don't do extracts or supplements with either.

Until I find even a shred of evidence that either is harmful, I will continue to do so.

you think 20 cloves per day is not megadosing ? capsaicin is going to burn your gastrointestinal tract. also causes urinary problems long term.

[Adaptogen]

I am addicted

addicted how ? what is the part that addicts you ?

addicted to strong flavors. For the same reason I like vinegar, chilies, fish sauce, tamarind, tart fruit, dark chocolate, horseradish, ginger, wasabi, kimchi - as a kid i can remember pouring palms full of raw garlic powder in my hands, and packing my mouth with it despite it burning my tongue and stomach..but then again i did that with most all of the spices in the cabinet

Edited by Adaptogen, 17 March 2013 - 01:35 AM.

[spermidine]

weirdo

[Clacksberg]

Suprised anybody's got a stomach left after that lot!

Just 1 raw clove a day here, but i notice a mood stimulating effect(positve)with just that.

[Darryl]

Paleontologist Peter Ward has a very interesting take on why we have a hormetic response to H2S: much higher levels were present during past global warming mass extinctions.

 

 

 

 

[hav]

 

It's garlic. I don't "megadose" it. It is part of my diet. Same with capsaicin. I don't do extracts or supplements with either.

Until I find even a shred of evidence that either is harmful, I will continue to do so.

 

...  capsaicin is going to burn your gastrointestinal tract. also causes urinary problems long term.

 

 

I think the capsaisin effect is dosage dependent.  Moderate amounts are known to desensitize the gi tract and relieve bladder pain.  The thing with capsaicin is that if you are not used to it, there might be some initial acclimation period before the good effects set in as you adjust to it.  This gi study used a dose of .5 mg 3x daily to good effect and mentioned another study that documented adjustment period:

 

http://onlinelibrary...006.03022.x/pdf

In a placebo-controlled trial of red pepper powder that contains capsaicin, Bortolotti et al. have demonstrated that the ingestion of a dose equivalent to 0.35 mg of capsaicin t.d.s induced upper abdominal symptoms in nine of 15 patients with functional dyspepsia during the first week. While two of the patients had to discontinue the trial due to the severity of initial symptoms, patients who continued the trial experienced an improvement of dyspeptic symptoms after 3 weeks. Repeated exposures of the oesophageal mucosa to capsaicin in patients with heartburn have also been reported to produce an analgesic effect after an initial phase of symptom worsening. Our findings of capsaicin-induced sensitization of chemoreceptors might explain the origin of inital symptoms in the previous studies. Likewise, repetitive capsaicin infusion over a 1-h period has sensitized the receptor responsible for symptom generation, most probably VR1. Sensitization of VR1 by capsaicin has long been recognized to be one of the characteristic features of this receptor.

 

I used to think I had a sensitive stomach and often experienced acid reflux but all that went away after I developed a taste for hot peppers. My favorite is Naga Bhut Jolokia from my garden.

 

Howard

[Journey2016]

Just like to say im on week two of brocmax and its given me a lift and improved wellbeing , this is ontop of my normal 500mg niagen and just added 100mg grape seed extract

Edited by Journey2016, 19 February 2017 - 10:41 PM.