Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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Articles by Walker, G. A.
Articles by Lithgow, G. J.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 56:B281-B287 (2001)
© 2001 The Gerontological Society of America

Heat Shock Protein Accumulation Is Upregulated in a Long-Lived Mutant of Caenorhabditis elegans

Glenda A. Walkera, Tiffany M. Whitec, Gawain McColla, Nicole L. Jenkinsa, Sandra Babichb, E. Peter M. Candidob, Thomas E. Johnsonc and Gordon J. Lithgowa

a School of Biological Sciences, University of Manchester, United Kingdom
b Department of Biochemistry, University of British Columbia, Vancouver, Canada
c Institute of Behavioral Genetics, University of Colorado, Boulder

Gordon J. Lithgow, The Buck Institute for Age Research, Novato, CA 94949 E-mail: glithgow{at}buckinstitute.org.

Decision Editor: John Faulkner, PhD

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 ß-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.




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