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 (H(2)S). Further examination showed that H(2)S increased longevity in C. elegans by modifying proteins in ways that stabilize their structures and enhance their functions. H(2)S has been shown to improve cardiovascular performance in mouse models of heart disease, and clinical trials are underway to test the effects of H(2)S on cardiovascular health in humans. These findings support the concept that nutrient deprivation, which slows protein synthesis and leads to ATF4-mediated H(2)S production, may extend lifespan by improving the function of the cardiovascular system and other systems that influence longevity in humans.