出版社:American Society for Biochemistry and Molecular Biology
摘要:Three major long-term effects of sterol deprivation in Caenorhabditis elegans are described. 1 ) The life expectancy of sterol-deprived wild-type animals is decreased by more than 40%. Similar decreases are found in animals carrying mutations in the daf-9 , daf-12 , daf-16 , and clk-1 genes, suggesting that previously described aging pathways involving these genes are not involved in the life-extending effects of sterols. 2 ) There is a premature loss of motility, measured by response to mild touch. 3 ) There is a rapid postreproductive onset of sarcopenia (muscle wasting) as measured by total body fluorescence in a myo3::GFP -expressing strain. We also report that five sterols (the desmethylsterols cholesterol, 7-dehydrocholesterol, and lathosterol and the 4α-methyl sterols lophenol and 4α-methyl-cholesta-Δ8(14)-en-3β-ol) are found in significant amounts at all stages of development and aging in cholesterol-fed animals. Supplying any one of these as the sole sterol confers similar protection from the long-term effects of sterol deprivation. These findings suggest that sterols are required continuously throughout the animal's life.