Hydrogen sulfide signaling, mTORC1 and Rapamycin - the Longevity Connection

Its interesting how a number of articles / papers have highlighted the longevity benefits of hydrogen sulfide, and now its now being tied to mTORC 1 inhibition.

Hydrogen sulfide is also a compound that the NIA ITP (intervention testing program) has tested starting in Cohort 12 (2016) for early life intervention and Cohort 14 (2018) for mid-life intervention for potential longevity effects in mice.

Here are the articles and papers:

ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1

https://www.nature.com/articles/s41467-022-28599-9#MOESM1

ATF-4 promotes longevity by activating canonical anti-ageing mechanisms, but also by elevating expression of the transsulfuration enzyme CTH-2 to increase hydrogen sulfide (H2S) production. This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines. The ATF-4/CTH-2/H2S pathway also mediates longevity and increased stress resistance from mTORC1 suppression. Increasing H2S levels, or enhancing mechanisms that H2S influences through persulfidation, may represent promising strategies for mobilising therapeutic benefits of the ISR, translation suppression, or mTORC1 inhibition.

And here is a previous 2018 writeup on hydrogen sulfide:

Aging Cells Rejuvenated When Hydrogen Sulfide Gives Splicing Factors a Lift

For aging cells, the Fountain of Youth gushes with hydrogen sulfide, which isn’t exactly convenient. Yes, in the laboratory, hydrogen sulfide has been shown to reverse some of the manifestations of cellular senescence, a state in which cells cease to divide but linger on, secreting inflammatory factors and driving age-related maladies. The hydrogen sulfide, however, is usually delivered by hydrogen sulfide donors in nonphysiological conditions. Could hydrogen sulfide’s benefits—which include, potentially, treatments against cancer, dementia, and diabetes—be obtained without relying on nonphysiological levels of hydrogen sulfide donors?

“Nearly half of the aged cells we tested showed signs of rejuvenating into young cell models,” says Dr. Harries, who attributed the “rescue of senescence phenotypes” to the upregulation of splicing factors, proteins that can cause genes to stop expressing one protein, and start expressing another.

“We used to think age-related diseases like cancer, dementia, and diabetes each had a unique cause, but they actually track back to one or two common mechanisms,” notes Dr. Harries. “This research focuses on one of these mechanisms, and the findings with our compounds have potentially opened up the way for new therapeutic approaches in the future. This may well be the basis for a new generation of antidegenerative drugs.”

The Research paper is here:

and other related papers:

and

H2S is a poisonous, water-soluble gas with a pungent odor of rotten eggs. At levels above 50ppm in air, H2S is acutely toxic to humans, whilst levels in excess of 300ppm are potentially fatal18. However, it is now clear that H2S is produced endogenously and that low endogenous levels may play a role in many biological processes19,20. H2S is synthesized endogenously in mammalian tissues by three types of enzymes: cystathionine-γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Importantly, H2S has been shown to be involved in several physiological and pathophysiological processes closely associated with ageing, including inflammation21,22, cancer23 and atherosclerosis24.

Source:

https://www.nature.com/articles/s41514-020-0044-8

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Interesting! Looks like taurine supplementation might be a safe and effective way to increase hydrogen sulfide:

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Isn’t hydrogen sulphide the gas that gives you “tummy ache”?