Authors: Walker, G A; White, T M; McColl, G; Jenkins, N L; Babich, S; Candido, E P; Johnson, T E; Lithgow, G J
Abstract: We present evidence for elevated levels of heat shock protein 16 (HSP16) in an intrinsically thermotolerant, long-lived strain of Caenorhabditis elegans during and after heat stress. Mutation of the age-1 gene, encoding a phosphatidylinositol 3-kinase catalytic subunit, results in both extended life span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphrodites. We subjected age-synchronous cohorts of worms to lethal and nonlethal thermal stress and observed the accumulation of a small (16-18 kd) heat-shock-specific polypeptide detected by an antibody raised against C. elegans HSP16. Strains carrying the mutation hx546 consistently accumulated HSP16 to higher levels than a wild-type strain. Significantly, overaccumulation of HSP16 in the age-1(hx546) strain following heat was observed throughout the adult life span. A chimeric transgene containing the Escherichia coli beta-galactosidase gene fused to a C. elegans HSP16-41 transcriptional promoter was introduced into wild-type and age-1(hx546) backgrounds. Heat-inducible expression of the transgene was elevated in the age-1(hx546) strain compared with the wild-type strain under a wide variety of heat shock and recovery conditions. These observations are consistent with a model in which Age mutations exhibit thermotolerance and extended life span as a result of elevated levels of molecular chaperones.
Keywords: Aging/*genetics; Animals; *Bacterial Proteins; Caenorhabditis elegans/enzymology/genetics/*metabolism; *Caenorhabditis elegans Proteins; Escherichia coli/enzymology; Gene Transfer Techniques; Genes, Reporter/genetics; Heat-Shock Proteins/genetics/*metabolism; *Hot Temperature; Longevity; Molecular Chaperones/metabolism; *Mutation; Phosphatidylinositol 3-Kinases/genetics; Promoter Regions, Genetic/genetics; Recombinant Fusion Proteins; Time Factors; Transcription, Genetic; Transgenes/genetics; Up-Regulation; beta-Galactosidase/genetics|
Journal: J Gerontol A Biol Sci Med Sci Volume: 56 Issue: 7 Pages: B281-7 Date: July 11, 2001 PMID: 11445592 |
Walker, G A, White, T M, McColl, G, Jenkins, N L, Babich, S, Candido, E P, Johnson, T E, Lithgow, G J (2001) Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 56: B281-7.
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