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.
Merris
Mark
M
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.
Kraeft
Jessica
J
Tint
G S
GS
Lenard
John
J
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