Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling

Minhua Zhang, Michal Poplawski, Kelvin Yen, Hui Cheng, Erik Bloss, Xiao Zhu, Harshil Patel, Charles V. Mobbs

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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 Ab42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Ab42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Ab42-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.

Original languageEnglish
Article numbere1000245
JournalPLoS Biology
Volume7
Issue number11
DOIs
StatePublished - Nov 2009

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