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 elega ns during and after heat stress. Mutation of the age-1 gene, encoding a pho sphatidylinositol 3-kinase catalytic subunit, results in both extended life span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphr odites. We subjected age-synchronous cohorts of worms to lethal and nonleth al thermal stress and observed the accumulation of a small (16-18 kd) heat- shock-specific polypeptide detected by an antibody raised against C. elegan s 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 b eta -galactosidase gene fused to a C. elegans HSP16-41 transcriptional prom oter was introduced into wild-type and age-1(hx546) backgrounds. Heat-induc ible expression of the transgene was elevated in the age-1(hx546) strain co mpared with the wild-type strain under a wide variety of heat shock and rec overy conditions. These observations are consistent with a model in which A ge mutations exhibit thermotolerance and extended life span as a result of elevated levels of molecular chaperones.