Research objective 22. Animal models of aging. In the course of our studies on the nature and functions of required sterols in the free-living nematode C. elegans we have discovered an apparent anti-aging effect of sterols, which is unmasked under conditions of sterol deprivation. We wish to understand this phenomenon on the cellular and molecular level. These effects are not mediated through the known agerelated pathways, and are therefore novel. We wish to identify the active sterols and to characterize the genes and pathways through which they act.
The aims of the present proposal are: (1) to determine whether sarcopenia (muscle wasting) is associated with steroldependent aging effects, as it is with aging generally; (2) to identify and quantitate the sterols that accumulate in an age-dependent fashion; (3) to identify genes that confer sterol-dependent phenotypes using RNAi. We expect to reveal novel mechanisms of sterol action in both development and aging, and we postulate that these will have parallels in higher organisms.
| Merris, Mark; Wang, Tongsheng; Soteropoulos, Patricia et al. (2007) Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4alpha-methylsterols. J Lipid Res 48:1159-66 |
