TY - JOUR
T1 - Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice
AU - Swindell, William R.
AU - Masternak, Michal M.
AU - Kopchick, John J.
AU - Conover, Cheryl A.
AU - Bartke, Andrzej
AU - Miller, Richard A.
N1 - Funding Information:
We thank Maggie Lauderdale and Jessica Sewald for technical and husbandry assistance. Two anonymous reviewers provided helpful comments on this manuscript. This work was supported by grants AG023122 (RAM), AG024824 (RAM), and AG198899 (AB). WRS is supported by NIA training grant T32-AG00114. J.J.K. is supported in part by the State of Ohio's Eminent Scholars Program, which includes a gift from Milton and Lawrence Goll and by WADA, and NIH (AG19899, DK075436 and CA099904).
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Growth hormone
KW - Insulin-like growth factor
KW - Longevity
KW - Snell
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=67349237490&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349237490&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2009.03.004
DO - 10.1016/j.mad.2009.03.004
M3 - Article
C2 - 19428459
AN - SCOPUS:67349237490
SN - 0047-6374
VL - 130
SP - 393
EP - 400
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 6
ER -