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

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. Brain ageing: Network map implicates immune-related genes The body’s immune response to microbes and damaged cells is associated with age-related cognitive decline, a gene network analysis shows. Jisook Moon from CHA University in Seoul, South Korea, and colleagues used published data on gene interactions to construct a network map of molecular determinants behind ageing in the brain. They identified clusters of genes involved in regulating immune responses, in particular those associated with the so-called complement system, which is responsible for activating inflammatory proteins that help clear the body of pathogens and infected host cells. The researchers suggest that complement-related genes may serve as a “master regulator” of brain aging. They propose that measuring expression of these genes could serve as a diagnostic biomarker for the reduced activity of synaptic transmission in brain that leads to cognitive impairment.