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Journal of Lipid Research, Vol. 45, 2044-2051, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Long-term effects of sterol depletion in C. elegans

Mark Merris^*, Jessica Kraeft^*, G. S. Tint^, and John Lenard^1,*

^* Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854
Department of Veterans Affairs New Jersey Health Care System, 385 Tremont Avenue, East Orange, NJ 07018
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07101

¹ To whom correspondence should be addressed. e-mail: lenard{at}umdnj.edu

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 4-methyl sterols lophenol and 4-methyl-cholesta-8(14)-en-3ß-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.

Abbreviations: 4MS, C4-methyl sterol; desMS, C4 desmethyl sterol; GFP, green fluorescent protein; 8(14) sterol, 4-methyl-cholesta-8(14)-en-3ß-ol

Supplementary key words Caenorhabditis elegans • cholesterol • 7-dehydrocholesterol • lathosterol • longevity • lophenol • sarcopenia

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