Ga. Walker et al., Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans, J GERONT A, 56(7), 2001, pp. B281-B287
Citations number
58
Categorie Soggetti
Public Health & Health Care Science","Medical Research General Topics
Journal title
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
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.