Decipher reliable biomarkers of brain aging by integrating literature-based evidence with interactome data.

Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9607880 Publication Model: Electronic Cited Medium: Internet ISSN: 2092-6413 (Electronic) Linking ISSN: 12263613 NLM ISO Abbreviation: Exp Mol Med Subsets: MEDLINE

Publication: Jan. 2013- : New York : Nature Publishing Group
Original Publication: Seoul : Korean Society of Medical Biochemistry and Molecular Biology, 1996-

Biomarkers* ; Connectome* ; Gene Regulatory Networks* ; Transcriptome*; Aging/*genetics ; Brain/*metabolism ; Brain/*physiopathology; Animals ; Computational Biology/methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; Humans ; Metabolic Networks and Pathways ; Mice ; Molecular Sequence Annotation ; Reproducibility of Results

Aging is an inevitable progressive decline in every physiological function and serves as a primary risk factor for cognitive decline and Alzheimer's disease. Thus, age-dependent impairments in cognitive function must be understood in association with general aging processes with an integrative approach in a systemic manner. An integrative aging gene network was constructed based on mutual molecular interactions using literature-curated interactome data and separated into functionally distinct modules. To investigate key surrogate biomarkers of the aging brain in the context of the general aging process, co-expression networks were built on post-mortem and Alzheimer's brain transcriptome data. In both the normal aging brain and the brain affected by Alzheimer's disease, the immune-related co-expression module was positively correlated with advancing age, whereas the synaptic transmission-related co-expression module was decreased with age. Importantly, the network topology-based analysis indicated that complement system genes were prioritized as a surrogate biomarker in evaluating the process of brain aging. Our public data-centered analysis coupled with experimental validation revealed that the complement system is likely to be a master regulator in initiating and regulating the immune system in the aging brain and could serve as reliable and surrogate biomarkers for the diagnosis of cognitive dysfunction.

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0 (Biomarkers)

Date Created: 20180414 Date Completed: 20190211 Latest Revision: 20220409

20240628

PMC5938059

10.1038/s12276-018-0057-6

29651153