Understanding the effects of Hydrogen Sulfide on Protein Homeostasis and Aging

2011 new Scholar Award in aging

All organisms must maintain homeostasis when conditions change in order to survive. With age the ability to maintain homeostasis declines, making it more difficult to survive injury or illness. Impaired homeostasis may also contribute to the increased incidence of many diseases with age. The goal of my lab is to understand fundamental mechanisms that underlie homeostatic mechanisms. Ultimately, these studies may provide insight that will enable us to develop interventions that will prevent the decline of homeostasis with age.

We are particularly interested in the effects of adaptation to hydrogen sulfide on homeostasis. Although best known as a toxic gas with the smell of rotten eggs, all animals naturally produce sulfide as part of cellular amino acid metabolism. Recent work has shown that exogenous sulfide can have beneficial effects in animals, improving survival in adverse conditions. We have developed C. elegans as a model to investigate the mechanistic basis of adaptation to sulfide. C. elegans grown with a small amount of sulfide in the air live 70% longer than those raised in normal room air. We hypothesize that adaptation to sulfide improves protein homeostasis, which we define as the ability to maintain coordination between protein synthesis, quality control and turnover. In the proposed research, we will measure the effects of adaptation to sulfide on protein homeostasis, and define molecular genetic factors that mediate these effects. Understanding adaptation to sulfide may provide new insight into strategies to mitigate defects in protein homeostasis that are associated with many diseases of aging, including debilitating neurodegenerative diseases.

Dana L. Miller Ph.D.
University of Washington