Molecular and Cellular Evidence for Age by Disease Interactions: Updates and Path Forward.

Molecular and Cellular Evidence for Age by Disease Interactions: Updates and Path Forward. Am J Geriatr Psychiatry. 2019 Jun 12;: Authors: Shukla R, Oh H, Sibille E Abstract Characterization of age-associated gene expression changes shows that the brain engages a specific set of genes and biologic pathways along a continuous life-long trajectory and that these genes and pathways overlap with those associated with brain-related disorders. Based on this correlative observation, we have suggested a model of age-by-disease interaction by which brain ageing promotes biologic changes associated with diseases and where deviations from expected age-related trajectories, due to biologic and environmental factors, contribute to defining disease risk or resiliency. In this review, we first evaluate various biomarkers that can be used to study age-by-disease interactions and then focus on transcriptome analysis (i.e., the set of all expressed genes) as a useful tool to explore this interaction. Using the specific example of brain-derived neurotrophic factor and brain-derived neurotrophic factor-associated genes, we then describe molecular events and mechanisms potentially contributing to age-by-disease interactions. Finally, we suggest that long-term biologic adaptations within distinct cellular components of cortical microcircuits, as determined by transcriptome analysis, may integrate and mediate the effects of ageing and diseases. Moving forw...
Source: The American Journal of Geriatric Psychiatry - Category: Psychiatry Tags: Am J Geriatr Psychiatry Source Type: research