Gene expression changes in the course of normal brain aging are sexually dimorphic

Nicole C. Berchtold, David H. Cribbs, Paul Coleman, Joseph Rogers, Elizabeth Head, Ronald Kim, Tom Beach, Carol Miller, Juan Troncoso, John Q. Trojanowski, H. Ronald Zielke, Carl W. Cotman

Research output: Contribution to journalArticle

270 Citations (Scopus)

Abstract

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on 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 in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh 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, 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 down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open 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 idea.

Original languageEnglish (US)
Pages (from-to)15605-15610
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number40
DOIs
StatePublished - Oct 7 2008
Externally publishedYes

Fingerprint

Gene Expression
Brain
Entorhinal Cortex
Genes
Prefrontal Cortex
Gene Ontology
Somatosensory Cortex
Protein Transport
Prosencephalon
Transcriptome
Hippocampus

Keywords

  • Entorhinal cortex
  • Hippocampus
  • Microarray
  • Sex differences
  • Superior frontal gyrus

ASJC Scopus subject areas

  • General

Cite this

Gene expression changes in the course of normal brain aging are sexually dimorphic. / Berchtold, Nicole C.; Cribbs, David H.; Coleman, Paul; Rogers, Joseph; Head, Elizabeth; Kim, Ronald; Beach, Tom; Miller, Carol; Troncoso, Juan; Trojanowski, John Q.; Zielke, H. Ronald; Cotman, Carl W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 40, 07.10.2008, p. 15605-15610.

Research output: Contribution to journalArticle

Berchtold, NC, Cribbs, DH, Coleman, P, Rogers, J, Head, E, Kim, R, Beach, T, Miller, C, Troncoso, J, Trojanowski, JQ, Zielke, HR & Cotman, CW 2008, 'Gene expression changes in the course of normal brain aging are sexually dimorphic', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 40, pp. 15605-15610. https://doi.org/10.1073/pnas.0806883105
Berchtold, Nicole C. ; Cribbs, David H. ; Coleman, Paul ; Rogers, Joseph ; Head, Elizabeth ; Kim, Ronald ; Beach, Tom ; Miller, Carol ; Troncoso, Juan ; Trojanowski, John Q. ; Zielke, H. Ronald ; Cotman, Carl W. / Gene expression changes in the course of normal brain aging are sexually dimorphic. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 40. pp. 15605-15610.
@article{eeaf565fb88d47d690aaacdbb39f9758,
title = "Gene expression changes in the course of normal brain aging are sexually dimorphic",
abstract = "Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on 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 in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh 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, 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 down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open 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 idea.",
keywords = "Entorhinal cortex, Hippocampus, Microarray, Sex differences, Superior frontal gyrus",
author = "Berchtold, {Nicole C.} and Cribbs, {David H.} and Paul Coleman and Joseph Rogers and Elizabeth Head and Ronald Kim and Tom Beach and Carol Miller and Juan Troncoso and Trojanowski, {John Q.} and Zielke, {H. Ronald} and Cotman, {Carl W.}",
year = "2008",
month = "10",
day = "7",
doi = "10.1073/pnas.0806883105",
language = "English (US)",
volume = "105",
pages = "15605--15610",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "40",

}

TY - JOUR

T1 - Gene expression changes in the course of normal brain aging are sexually dimorphic

AU - Berchtold, Nicole C.

AU - Cribbs, David H.

AU - Coleman, Paul

AU - Rogers, Joseph

AU - Head, Elizabeth

AU - Kim, Ronald

AU - Beach, Tom

AU - Miller, Carol

AU - Troncoso, Juan

AU - Trojanowski, John Q.

AU - Zielke, H. Ronald

AU - Cotman, Carl W.

PY - 2008/10/7

Y1 - 2008/10/7

N2 - Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on 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 in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh 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, 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 down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open 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 idea.

AB - Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on 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 in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh 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, 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 down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open 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 idea.

KW - Entorhinal cortex

KW - Hippocampus

KW - Microarray

KW - Sex differences

KW - Superior frontal gyrus

UR - http://www.scopus.com/inward/record.url?scp=55749105400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55749105400&partnerID=8YFLogxK

U2 - 10.1073/pnas.0806883105

DO - 10.1073/pnas.0806883105

M3 - Article

C2 - 18832152

AN - SCOPUS:55749105400

VL - 105

SP - 15605

EP - 15610

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 40

ER -