Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
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.
Zhang
Minhua
M
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America.
Poplawski
Michal
M
Yen
Kelvin
K
Cheng
Hui
H
Bloss
Erik
E
Zhu
Xiao
X
Patel
Harshil
H
Mobbs
Charles V
CV
D000375:Aging / Q000378:metabolism*; D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D036961:Matrix Attachment Region Binding Proteins; C469541:Satb1 protein, mouse; D050882:CREB-Binding Protein