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


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
Issue number11
StatePublished - Nov 2009


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