Data Set Group2: GSE11882 UCI Human Affy U133 Plus2 (Sep13) RMA

Data Set: GSE11882 UCI Human Hippocampus Affy U133 Plus2 (Sep13) RMA GN Accession: GN461 GEO Series: GSE11882 Title: Gene expression changes in the course of normal brain aging are sexually dimorphic Organism: Human (Homo sapiens, hg19) Group: Aging-Brain-UCI Tissue: Hippocampus mRNA Dataset Status: Public Platforms: Affy Human Genome U133 Plus 2.0 Array (GPL570) Normalization: RMA

Contact Information Nicole Claudia Berchtold University of California, Irvine 1226 Gillespie Neuroscience Facility Irvine, CA 92697-4540 USA Tel. 949 824 6071 nberchto@uci.edu Website Download datasets and supplementary data files GN461_MeanDataAnnotated_rev081815.txt (N/A) GN461_StdError_rev081815.txt (N/A)

Specifics of this Data Set:

None

Summary:

Gene expression profiles were assessed in the hippocampus (HC), entorhinal cortex (EC), superior frontal gyrus (SG), and postcentral gyrus (PCG) across the lifespan of 63 cognitively intact individuals from 20-99 years old. New perspectives on the global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age (20-59 vs. 60-99) in the superior frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the 6th-7th decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident across the lifespan, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with downregulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with more widespread activation in the female brain. These data open new opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain, and suggest that this balance is set differently in males and females, an intriguing and novel idea. HgU133plus2.0 microarray chips were used to profile gene expression in 4 brain regions of cognitively intact humans, across the adult lifespan (ages 20-99).

About the cases used to generate this set of data:

About the tissue used to generate this set of data:

About the array platform:

About data values and data processing:

Notes:

Experiment Type:

Postmortem brain tissue was collected from ADRC brain banks. Cases were preferentially selected where 3 or more brain regions were available.

Contributor:

Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, Beach T, Miller C, Troncoso J, Trojanowski JQ, Zielke HR, Cotman CW

Citation:

Berchtold NC, Cribbs DH, Coleman PD, Rogers J et al. Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci U S A 2008 Oct 7;105(40):15605-10. PMID: 18832152

Data source acknowledgment:

Study Id:

175

• The UT Center for Integrative and Translational Genomics
• NIGMS Systems Genetics and Precision Medicine project (R01 GM123489, 2017-2021)
• NIDA NIDA Core Center of Excellence in Transcriptomics, Systems Genetics, and the Addictome (P30 DA044223, 2017-2022)
• NIA Translational Systems Genetics of Mitochondria, Metabolism, and Aging (R01AG043930, 2013-2018)
• NIAAA Integrative Neuroscience Initiative on Alcoholism (U01 AA016662, U01 AA013499, U24 AA013513, U01 AA014425, 2006-2017)
• NIDA, NIMH, and NIAAA (P20-DA 21131, 2001-2012)
• NCI MMHCC (U01CA105417), NCRR, BIRN, (U24 RR021760)