As I think we’ve discussed here in the past, Hydrogen Sulfide is a compound/gas that the NIA ITP program is testing for increased lifespan / healthspan effects, at a dosing of 240ppm, in the Cohort 12 and Cohort 15 groups (source: NIA ITP Compounds).
Here is a new review paper on Hydrogen Sulfide that has just come out:
Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of agerelated diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionarybased adaptive response to low-level stress, is emerging as a promising paradigm in the field of antiaging.
Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.
Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated *Caenorhabditis elegans
by Adriana Raluca Vintila, Luke Slade, Michael Cooke, Craig R. G. Willis, Roberta Torregrossa, Mizanur Rahman, Taslim Anupom, Siva A. Vanapalli, Christopher J. Gaffney, Nima Gharahdaghi, Csaba Szabo, Nathaniel J. Szewczyk, Matthew Whiteman and Timothy Etheridge, 31 July 2023, Proceedings of the National Academy of Sciences . DOI: 10.1073/pnas.2216141120
AP39 seems to be the substance being investigated but it’s unclear (from my brief Googling) whether this is close to being commercially available. Is that your understanding too, or are there other drugs or supplements that act as a mitochondrial HS2 donor?
This is the first research I’ve seen on it, and given that the study is in nematode worms, it suggests it is many years away from commercial availability (or even Phase 2 and phase 3 clinical trials)… so not something anyone can expect to act on any time soon.
and the startup company pipeline suggests this also:
There is a theory that Acarbose works because it stops carbohydrate being digested. The carbohydrate then travels further along the bowel where it is broken down by bacteria, which produce gas. This creates the excessive flatulence noted by those who use acarbose.
But an “extension” to the theory is that at least some of the gas produced is hydrogen and that longevity benefits ascribed to acarbose are, in fact, due to hydrogen.
desertshores (and I joined him) in making hydrogen water.
[desertshores]
I like that theory. BTW I am going to make hydrogen-enriched water and drink 500ml/day and see what if any effects it has on my biomarkers.
Didn’t work for me. Maybe it is the contraption I used. I could either buy commercial hydrogen sulfide producers, or take those hydrogen producing tablets.
My rule of thumb is, unless there are definitive studies for the benefits of a particular supplement or routine, I only do it for a few months, and if I don’t see any detectable results in my blood work or feel a subjective improvement I stop taking it. Otherwise, my supplement list would be much longer than it is.
I grew tired of the hydrogen water after a few months because of the added hassle of making it.
There were no measurable or subjective results in my case.
If you find an acceptable hydrogen sulfide producer that isn’t too obnoxious let us know.
I have travelled around the Black Sea area and it is possible to find springs or spas there that contain H2S. I don’t know the concentration of the gas but you can smell/taste it. Some people in the area drink small quantities regularly. I have wondered if they knew of health/longevity benefits, although this would not be a “slow release” form of H2S.
H2S is an important endogenous regulator of the immune system. Ou et al. demonstrate that apoptotic cells and vesicles produce H2S to maintain immune homeostasis and inhibit Th17 cell differentiation via sulfhydration of Sep15C38.
Highlights
Apoptotic cells are an important resource providing endogenous H2S
H2S inhibits the aberrant Th17 cell differentiation via sulfhydration of Sep15
H2S from apoptotic cells ameliorates murine systemic lupus erythematosus phenotypes
Summary:
Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H2S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H2S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim/(B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H2S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H2S. Moreover, apoptotic cells and vesicles (apoVs) express key H2S-generating enzymes and generate a significant amount of H2S, indicating that apoptotic metabolism is an important source of H2S. Mechanistically, H2S sulfhydrates selenoprotein F (Sep15) to promote signal transducer and activator of transcription 1 (STAT1) phosphorylation and suppress STAT3 phosphorylation, leading to the inhibition of Th17 cell differentiation. Taken together, this study reveals a previously unknown role of apoptosis in maintaining H2S homeostasis and the unique role of H2S in regulating Th17 cell differentiation via sulfhydration of Sep15* *C38.
Although harmful in large quantities, hydrogen sulfide may ameliorate the health consequences of aging when small doses are applied to the mitochondria.
The dose makes the poison. That adage is just as true of hazardous chemicals as it is of life-sustaining substances like water and oxygen. For instance, foul-smelling hydrogen sulfide (H2S) gas can be lethal if someone inhales too much in a sewer or a swamp, and yet, human cells produce it in small quantities as a critical signaling molecule.
In a recent study published in the Proceedings of the National Academy of Sciences, a team of researchers evaluated the effects of a mitochondria-targeted H2S treatment on the health and longevity of Caenorhabditis elegans nematodes (1). The researchers hope that their work will inform better strategies for using the gas to improve health in humans, particularly by slowing the progression of muscular and neurological decline as well as other diseases that typically affect the elderly. They’re not necessarily expecting to find the elixir of life. “It’s just delaying the onset of age and maintaining health for as long as possible,” said Matt Whiteman, one of the leaders of the project and a pharmacologist at the University of Exeter.
Most diseases will have a mitochondrial dysfunction component to them. If you can fix [it], you’ve got a high chance of at least delaying the disease progression or hopefully reversing some of it.
Matt Whiteman, University of Exeter
Whiteman has been exploring the health benefits of treating animals with low quantities of externally produced H2S for years. He became particularly interested in understanding the effects of H2S on mitochondria because evidence suggests that H2S performs a number of biological functions that support mitochondrial health, such as facilitating mitochondrial DNA repair and providing antioxidant protection (2). Aging bodies tend to lose their mitochondria, but treating these organelles with H2S could prevent that loss and alleviate associated health consequences (3).
This is where Allicin (an HS donor) is thought to have merit. I use Allicin Max which is processed from garlic, it is stored in little airtight containers to prevent oxidation. An alternative is eating garlic.
