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Title: Growth Hormone Receptor and IGF-I Deficiency is Associated with Resistance to DNA Damage and Very Low Cancer and Diabetes Incidence in Humans      
dateReleased:
12-25-2010
description:
Growth Hormone Receptor Deficiency (GHRD) in mice causes life span extension and a major increase in the portion of animals that die without detectable pathologies including cancer and insulin resistance. During a 22-year monitoring of a cohort of 0-88 year old Ecuadorian GHRD subjects with severe IGF-I deficiency developed we observed a single, non-lethal malignancy and no diabetes. To understand the mechanisms responsible for this low disease incidence we incubated Human Mammary Epithelial Cells (HMECs) with serum from either GHRD or control subjects. GHRD serum not only protected mammary cells against hydrogen peroxide-dependent DNA damage but also promoted cell death in severely damaged cells by a mechanism blocked by IGF-I. The gene expression or DNA damage profile in epithelial cells exposed to GHRD serum, fibroblasts lacking the IGF-I receptor, and long-lived yeast lacking homologs of IGF-I signaling genes point to stress resistance transcription factors and SOD2 as mediators of GHRD-associated protection. These results provide evidence for a role of GH and IGF-I deficiency in promoting healthy aging in humans. Primary Human Mammalian Epithelial Cells (HMECs), were cultured in HMEC medium (ScienCell) at 37oC and 5% CO2 in Poly-L-Lysine coated culture dishes (Sigma). Treatment consisted of cells being stimulated with HMEC basal medium containing either 15% GHRD serum or 15% control serum for 6 hours. Cells were then harvested and processed for RNA extraction.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-21980
refinement:
raw
alternateIdentifiers:
21980
keywords:
functional genomics
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-MEXP-1171
name:
Illumina HumanHT-12 v3.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-21980/E-GEOD-21980.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-21980/E-GEOD-21980.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21980
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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