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

William R. Swindell, Michal M. Masternak, John J. Kopchick, Cheryl A. Conover, Andrzej Bartke, Richard A. Miller

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)393-400
Number of pages8
JournalMechanisms of Ageing and Development
Volume130
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Growth hormone
  • Insulin-like growth factor
  • Longevity
  • Snell
  • Stress

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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