An integrated transcriptomic analysis of brain aging and strategies for healthy aging

Background: It is been noted that the expression levels of numerous genes undergo changes as individuals age, and aging stands as a primary factor contributing to age-related diseases. Nevertheless, it remains uncertain whether there are common aging genes across organs or tissues, and whether these aging genes play a pivotal role in the development of age-related diseases.

Methods: In this study, we screened for aging genes using RNAseq data of 32 human tissues from GTEx. RNAseq datasets from GEO were used to study whether aging genes drives age-related diseases, or whether anti-aging solutions could reverse aging gene expression.

Results: Aging transcriptome alterations showed that brain aging differ significantly from the rest of the body, furthermore, brain tissues were divided into four group according to their aging transcriptome alterations. Numerous genes were downregulated during brain aging, with functions enriched in synaptic function, ubiquitination, mitochondrial translation and autophagy. Transcriptome analysis of age-related diseases and retarding aging solutions showed that downregulated aging genes in the hippocampus further downregulation in Alzheimer's disease but were effectively reversed by high physical activity. Furthermore, the neuron loss observed during aging was reversed by high physical activity.

Conclusion: The downregulation of many genes is a major contributor to brain aging and neurodegeneration. High levels of physical activity have been shown to effectively reactivate these genes, making it a promising strategy to slow brain aging.