Molecular aging in human prefrontal cortex is selective and continuous throughout adult life

Background: Aging leads to morphologic and functional changes in the brain and is associated with increased risk for-psychiatric and neurological disorders. Methods: To identify age-related transcriptional changes in the human brain, we profiled gene expression in two prefrontal cortex (PFC) areas in postmortem samples from 39 subjects, ranging in age from 13 to 79 years. Results: Robust transcriptional age-related changes were identified,for at least 540 genes. Gene expression correlates of aging were highly specific, and the large majority of the 22, 000 transcripts investigated were unaffected by age. Across subjects, changes were progressive throughout adult life and accurately predicted chronological age. Age-upregulated transcripts were mostly of glial origin and related to inflammation and cellular defenses, whereas downregulated genes displayed mostly neuron-enriched transcripts relating to cellular communication and signaling. Conclusions: Continuous changes in gene expression with increasing age revealed a molecular profile of aging in human PFC. The restricted scope of the transcript changes suggests cellular populations or,functions that are selectively vulnerable during aging. Because age-related gene expression changes begin early in adulthood and are continuous throughout life, our results suggest the possibility of identifying early cellular mechanisms that may be engaged in preventive or detrimental age-related brain functions.