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Evolution of the Aging Brain Transcriptome and Synaptic Regulation

Loerch, PM; Lu, T; Dakin, KA; Vann, JM; Isaacs, A; Geula, C; Wang, J; ... Yankner, BA; + view all (2008) Evolution of the Aging Brain Transcriptome and Synaptic Regulation. PLOS ONE , 3 (10) , Article e3329. 10.1371/journal.pone.0003329. Green open access

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Abstract

Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

Type: Article
Title: Evolution of the Aging Brain Transcriptome and Synaptic Regulation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0003329
Publisher version: http://dx.doi.org/10.1371/journal.pone.0003329
Language: English
Additional information: © 2008 Loerch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by grants from the National Institute on Aging (grant numbers AG26651, AG27040, AG27916), and an Ellison Medical Foundation Senior Scholar award to B.A.Y.. P.L. was supported by NIH training grant T32GM074897.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/91986
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