role of cbp and satb-1 in aging, dietary restriction, and insulin-like signalingcbp和satb-1老化的作用,限制饮食和胰岛素样信号.pdfVIP

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling 1 1 1 1 1 1 1 Minhua Zhang , Michal Poplawski , Kelvin Yen , Hui Cheng , Erik Bloss , Xiao Zhu , Harshil Patel , Charles V. Mobbs1,2* 1 Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Department of Geriatrics, 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 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 b