Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
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DOI：
10.1371/journal.pbio.1000245
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发表时间：
2009-11
期刊：
影响因子：
9.8
通讯作者：
Mobbs CV
中科院分区：
文献类型：
--
作者：
Zhang M;Poplawski M;Yen K;Cheng H;Bloss E;Zhu X;Patel H;Mobbs CV
Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging. How dietary restriction (DR) increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP) and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1) is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR) and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Aβ42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Aβ42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Aβ42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway. The simple manipulation of dietary restriction (DR) (reduction of caloric intake by about 30% in rodents) produces robust increases in lifespan and slows the development of almost all age-related diseases, including cancer and neurological diseases. This relationship between dietary restriction and longevity is observed in most models in which the effect of DR has been tested. Thus, understanding how DR produces its protective mechanisms would have potentially profound implications for the treatment of age-related diseases, including possibly the development of a “magic bullet” for these diseases. In the present study we have discovered that DR induces a transcription factor, CBP, and additional factors that work with CBP to control the expression of other genes involved in determination of lifespan. When we blocked the DR-mediated increase in CBP and associated factors, we blocked all the protective effects of DR on lifespan extension, on the slowed rate of aging, and on protection against pathology in a model of Alzheimer's disease. Further, in mice expression of CBP and a CBP-interacting factor positively predicted lifespan, and expression of both factors decreased with age and in diabetes. Finally, pharmacological manipulations that mimicked enhanced CBP activity increased lifespan and reduced pathology in a model of Alzheimer's disease.
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影响因子：
64.8
作者：
Honjoh, Sakiko;Yamamoto, Takuya;Nishida, Eisuke
通讯作者：
Nishida, Eisuke
影响因子：
64.8
作者：
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影响因子：
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通讯作者：
JOHNSON, TE
DOI：
10.1073/pnas.95.22.13091
发表时间：
1998-10-27
影响因子：
11.1
作者：
Lakowski, B;Hekimi, S
通讯作者：
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影响因子：
64.8
作者：
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