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

TitleResilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.
Publication TypeJournal Article
Year of Publication2017
AuthorsPabba M, Scifo E, Kapadia F, Nikolova YS, Ma T, Mechawar N, Tseng GC, Sibille E
JournalNeurobiol Aging
Date Published2017 Oct

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.

Alternate JournalNeurobiol. Aging
PubMed ID28750307
PubMed Central IDPMC5581682
Grant ListR01 MH093723 / MH / NIMH NIH HHS / United States