Hydrogen sulfide: the gas that fuels longevity

Abstract

The molecular determinants of lifespan can be examined in animal models with the long-term objective of applying what is learned to the development of strategies to enhance longevity in humans. Here, we comment on a recent publication examining the molecular mechanisms that determine lifespan in worms, Caenorhabditis elegans (C. elegans), where it was shown that inhibiting protein synthesis increased levels of the transcription factor, ATF4. Gene expression analyses showed that ATF4 increased the expression of genes responsible for the formation of the gas, hydrogen sulfide (H2S). Further examination showed that H2S increased longevity in C. elegans by modifying proteins in ways that stabilize their structures and enhance their functions. H2S has been shown to improve cardiovascular performance in mouse models of heart disease, and clinical trials are underway to test the effects of H2S on cardiovascular health in humans. These findings support the concept that nutrient deprivation, which slows protein synthesis and leads to ATF4-mediated H2S production, may extend lifespan by improving the function of the cardiovascular system and other systems that influence longevity in humans.

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

“…[188] Studies using various model organisms have shown that decreased protein synthesis, decreased translation, and increased fidelity of protein synthesis slow aging and extend lifespan. [226,124,227,34,131] Signaling pathways involved in CLS extension also influence translational regulation. For example, the TOR and PKA pathways regulate ribosomal gene transcription in S. cerevisiae.…”

“…[130] Therefore, daf-16 may be required for lifespan extension by H 2 S. Furthermore, H 2 S is reportedly important for extending the lifespan of nematodes by inhibiting TORC1 or protein translation. [124,131] In addition, H 2 S is involved in the aging of mammals. [132][133][134]…”

“…H 2 S is a potent endogenous gasotransmitter that converts protein cysteine thiols and protein sulfenic acids to persulfides during persulfidation. [ 124 ] H 2 S extends CLS in S. cerevisiae and lifespan in C. elegans . [ 125–128 ] In budding yeast, the AGC‐type protein kinase Ypk2, which regulates cell wall integrity, may be involved in H 2 S‐release–induced CLS extension by using the H 2 S donor, NaHS.…”