Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling
Dave Saum
http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000245
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
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-1also attenuates lifespan
extension by bDR, but not other protocols of DR. In a transgenic A�42 model
of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and
accelerates A�42-related pathology. Furthermore, consistent with the
function of CBP as a histone acetyltransferase, drugs that enhance histone
acetylation increase lifespan and reduce A�42-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.
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http://www.sciencedaily.com/releases/2009/11/091118143217.htm
Science News Share Blog Cite Print Email BookmarkScientists Find
Molecular Trigger That Helps Prevent Aging and Disease
ScienceDaily (Nov. 23, 2009) � Researchers at Mount Sinai School of Medicine
set out to address a question that has been challenging scientists for
years: How does dietary restriction produce protective effects against aging
and disease? And the reverse: how does overconsumption accelerate
age-related disease?