Long-term effects of sterol depletion in C. elegans: sterol content of synchronized wild-type and mutant populations.
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 4alpha-methyl sterols lophenol and 4alpha-methyl-cholesta-Delta8(14)-en-3beta-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.
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Mark
M
Merris
Jessica
J
Kraeft
G S
GS
Tint
John
J
Lenard
D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002775:Cholestadienols / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003684:Dehydrocholesterols / Q000378:metabolism; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D009132:Muscles / Q000473:pathology; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D013261:Sterols / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002775:Cholestadienols; C410905:DAF-12 protein, C elegans; D003684:Dehydrocholesterols; D051858:Forkhead Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D013261:Sterols; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D049452:Green Fluorescent Proteins; C001521:lathosterol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; C016705:7-dehydrocholesterol; C486228:DAF-9 protein, C elegans