PT - JOURNAL ARTICLE AU - Ulaş Işıldak AU - Mehmet Somel AU - Janet M. Thornton AU - Handan Melike Dönertaş TI - Meta-Analysis of the Gene Expression Profiles of Aging Brain Reveals a Consistent Increase in Heterogeneity AID - 10.1101/595249 DP - 2019 Jan 01 TA - bioRxiv PG - 595249 4099 - http://biorxiv.org/content/early/2019/07/25/595249.short 4100 - http://biorxiv.org/content/early/2019/07/25/595249.full AB - In largely non-mitotic tissues such as the brain, cells are prone to a gradual accumulation of stochastic genetic and epigenetic alterations. This may lead to increased gene expression variation between cells and possibly also between individuals over time. Although increased inter-individual heterogeneity in gene expression during brain aging was previously reported, whether this process starts during development or if it is mainly restricted to the aging period has not yet been studied. The regulatory dynamics and functional significance of putative age-related heterogeneity are also unknown. Here we address these issues by a systematic analysis of 19 transcriptome datasets from diverse human brain regions in human covering the whole postnatal lifespan. Among all datasets, we observed a significant increase in inter-individual gene expression heterogeneity during aging (20 to 98 years of age) compared to postnatal development (0 to 20 years of age). Increased heterogeneity during aging was consistent among different brain regions at the gene level. Genes showing increased heterogeneity were associated with biological processes that are known to be important for lifespan regulation and neuronal function, including longevity regulating pathway, autophagy, mTOR signaling, axon guidance, and synaptic function. Overall, our results show that increased gene expression heterogeneity during aging is a general effect in the human brain, and may influence aging-related changes in brain functions. We also provide the necessary functions to calculate heterogeneity change with age as an R package, ‘hetAge’.