Abstract
Aging is a biologically universal event, and yet the key events that drive aging are still poorly understood. One approach to generate new hypotheses about aging is to use unbiased methods to look at change across lifespan. Here, we have examined gene expression in the human dorsolateral frontal cortex using RNA- Seq to populate a whole gene co-expression network analysis. We show that modules of co-expressed genes enriched for those encoding synaptic proteins are liable to change with age. We extensively validate these age-dependent changes in gene expression across several datasets including the publically available GTEx resource which demonstrated that gene expression associations with aging vary between brain regions. We also estimated the extent to which changes in cellular composition account for age associations and find that there are independent signals for cellularity and aging. Overall, these results demonstrate that there are robust age-related alterations in gene expression in the human brain and that genes encoding for neuronal synaptic function may be particularly sensitive to the aging process.
Highlights
Aging is an inherent, multidimensional biological process that includes aspects of physical and behavioral changes
Consistent with prior studies using microarrays, gene expression in the brain appears to be robustly organized into modules to which weighted gene correlation network analysis (WGCNA) is sensitive[31,32,33,34,35,36,37]. These modules of gene expression reflect organization of brain structures and function, being readily categorized by gene ontology related to specific cell types or subcellular organelles, the latter including mitochondria and synaptic vesicles
Our dataset identified a series of associations of gene expression with aging, including several that have been proposed previously based on microarrays[7,27]
Summary
Multidimensional biological process that includes aspects of physical and behavioral changes. The results provide a series of newly identified changes in human brain aging with a strong regional association with loss of synaptic gene expression.
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