期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 130, 期 6, 页码 393-400出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2009.03.004
关键词
Growth hormone; Insulin-like growth factor; Longevity; Snell; Stress
资金
- NIA [T32-AG00114]
- State of Ohio's Eminent Scholars Program
- Milton and Lawrence Goll
- WADA
- NIH [AG19899, DK075436, CA099904]
- [AG023122]
- [AG024824]
- [AG198899]
- NATIONAL CANCER INSTITUTE [R01CA099904] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R15DK075436] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [U19AG023122, R01AG019899, T32AG000114, P01AG031736, P30AG024824] Funding Source: NIH RePORTER
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 CH/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. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
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