Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans.
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.
Walker
G A
GA
School of Biological Sciences, University of Manchester, United Kingdom.
White
T M
TM
McColl
G
G
Jenkins
N L
NL
Babich
S
S
Candido
E P
EP
Johnson
T E
TE
Lithgow
G J
GJ
D000375:Aging / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D004926:Escherichia coli / Q000201:enzymology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008136:Longevity; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins; D013997:Time Factors; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000235:genetics
D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase; C113725:HspA protein, bacteria