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

Mech Ageing Dev. 2009 Jun;130(6):393-400. doi: 10.1016/j.mad.2009.03.004. Epub 2009 Apr 8.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Cell Line
  • Disease Models, Animal
  • Dwarfism, Pituitary / genetics*
  • Dwarfism, Pituitary / metabolism
  • Female
  • Fibroblasts / metabolism
  • Growth Hormone / administration & dosage
  • Growth Hormone / metabolism*
  • Heat-Shock Proteins / genetics*
  • Injections
  • Insulin-Like Growth Factor I / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Longevity / genetics*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Myocardium / metabolism
  • Prolactin / metabolism
  • RNA, Messenger / metabolism*
  • Thyrotropin / metabolism
  • Transcription Factor Pit-1 / genetics

Substances

  • Carrier Proteins
  • Heat-Shock Proteins
  • Pit1 protein, mouse
  • RNA, Messenger
  • Transcription Factor Pit-1
  • Insulin-Like Growth Factor I
  • Prolactin
  • Thyrotropin
  • Growth Hormone
  • somatotropin-binding protein