Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice.
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.
University of Michigan, Department of Pathology and Geriatrics Center, Ann Arbor, MI 48109-2200, USA. wswindel@med.umich.edu
William R
WR
Swindell
Michal M
MM
Masternak
John J
JJ
Kopchick
Cheryl A
CA
Conover
Andrzej
A
Bartke
Richard A
RA
Miller
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D004195:Disease Models, Animal; D004393:Dwarfism, Pituitary / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics*; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D050817:Transcription Factor Pit-1 / Q000235:genetics
D002352:Carrier Proteins; D013006:Growth Hormone; D006360:Heat-Shock Proteins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D012333:RNA, Messenger; D013972:Thyrotropin; D050817:Transcription Factor Pit-1; C494185:Pou1f1 protein, mouse; C051815:somatotropin-binding protein