C. ELEGANS AS A MODEL FOR HORMETIC LIFE EXTENSION.





J. R. Cypser and T. E. Johnson

Institute for Behavioral Genetics, University of Colorado, 1480 30th Street, Boulder, CO 80303




The nematode C. elegans has been used extensively to demonstrate that mutations in single genes can cause profound extensions of life span1-6 (Age phenotype). Hormesis (benefits derived from exposure to low levels of an otherwise toxic stressor) has been shown to increase life expectancy in a wide variety of organisms7-9 in addition to increased stress resistance10. The purpose of this study was to establish the utility of C. elegans as a model of hormetic life extension and stress resistance. Using survival assays and selected chemical and physical stressors, we have extensively documented hormesis for both stress resistance and life span in C. elegans. We find that the hormetic responses of life span extension and stress resistance correlate closely in the worm, similarly to what has been observed in Age mutants. Additionally, we have found that pretreatment with either of two stressors, oxygen or a reactive oxygen species (juglone) induces subsequent resistance to the other stressor. These results may reflect an underlying paradigm of resistance to oxidative stress that might explain hormetic life extension as induced resistance to the endogenous stress of free radicals, postulated by Harmon11 to be a proximate cause of aging. Finally, we have found preliminary evidence that certain genes of the dauer formation pathway, already known to be required for the life extension seen in single-gene Age mutants, are also required for the increased life span associated with hormesis.
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Key words: C. elegans, hormesis, stress resistance, dauer







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