Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice

Abstract

Heat shock proteins (HSPs) maintain proteostasis and may protect against age-associated pathology caused by protein malfolding. In Caenorhabditis elegans, the lifespan extension and thermotolerance in mutants with impaired insulin/IGF signals depend partly on HSP elevation. Less is known about the role of HSPs in the increased lifespan of mice with defects in GH/IGF-I pathways. We measured HSP mRNAs in liver, kidney, heart, lung, muscle and cerebral cortex from long-lived Pit1( dw/dw) Snell dwarf mice. We found many significant differences in HSP mRNA levels between dwarf and control mice, but these effects were complex and organ-specific. We noted 15 instances where HSP mRNAs were lower in Pit1( dw/ dw) liver, kidney, or heart tissues, and 14/15 of these were also seen in Ghr( -/-) mice, which lack GH receptor. In contrast, of 12 examples where HSP mRNAs were higher in Snell liver, kidney, or heart, none were altered in Ghr( -/-) mice. Four liver mRNAs were depressed in both Pit1( dw/ dw) and Ghr(-/-) mice, and each of these was elevated by GH injection in Ames ( Prop1( df/df)) dwarf mice, consistent with the hypothesis that these declines depended on GH and/or IGF-I. Contributions of chaperones to longevity in mice may be more complex than those inferred from C. elegans.