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Neurobiol Aging. 2017 Oct;58:180-190. doi: 10.1016/j.neurobiolaging.2017.06.023. Epub 2017 Jul 5.

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

Author information

1
Campbell Family Mental Health Research Institute of CAMH, Neurobiology of Depression and Aging, Toronto, Ontario, Canada.
2
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
3
McGill Group for Suicide Studies, Douglas Mental Health University Institute, Verdun, Quebec, Canada; Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
4
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
5
Campbell Family Mental Health Research Institute of CAMH, Neurobiology of Depression and Aging, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: Etienne.sibille@camh.ca.

Abstract

The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age.

KEYWORDS:

Cortex; Layer 2/3; Normal aging; Proteomics and RNA-Seq

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