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PLoS Biol. 2009 Nov;7(11):e1000245. doi: 10.1371/journal.pbio.1000245. Epub 2009 Nov 17.

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

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  • 1Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America.

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 Abeta42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Abeta42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Abeta42-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.

PMID:
19924292
[PubMed - indexed for MEDLINE]
PMCID:
PMC2774267
Free PMC Article

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