Hydrogen Sulfide and Mechanisms of Aging

Researchers here discuss an investigation of the role of hydrogen sulfide in cell function and long-term health. Upregulation of hydrogen sulfide levels is an approach to modifying metabolism in order to modestly slow aging, and researchers here note an overlap with the mechanisms of calorie restriction, in that low nutrient levels increase the production of hydrogen sulfide in the body. While scientifically interesting, this sort of intervention is hardly the way forward to meaningfully extend the healthy human life span. We need better, more targeted approaches that do more to directly reverse the damage and dysfunction of aged tissues.

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.

Link: https://doi.org/10.20517/jca.2022.16

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