Hippocampal transcriptome deconvolution reveals differences in cell architecture of not demented elderly subjects underwent late-life physical activity

Recent findings demonstrated that physical exercise has a powerful role in improving cognitive function and delaying age-associated neurological decline. However, to date, there is a lack of information regarding the effect of physical activity (PA) on brain cells architecture. In this paper, we hypothesized that PA could play a role in the transcriptional changes of genes that enrich the main cells of central nervous system (CNS). From NCBI, we selected a microarray dataset composed of the human hippocampi (GSE110298) from 23 cognitively intact clinical cases (NDHSs) (aged 87.4±6.3 years) selected to from the Rush Memory and Aging Project (MAP). The significantly expressed genes, obtained comparing hippocampi from subjects who underwent Low Physical Activity (LPA) vs those who performed High Physical Activity (HPA), were overlapped with the main genes enriching the CNS cells, obtained from the public human brain single-cell RNA-sequencing dataset (GSE67835), in order to determine the respective weighted percentages of significantly expression genes modulation (WPSEG). In NDHSs underwent HPA, the WPSEG was higher for Neurons, Dendritic Development, Synaptic transmission genes and Axon Development. In addition, in NDHSs underwent LPA we observed high expression of genes enriching Oligodendrocytes, Microglia, and Endothelial cells. Furthermore, neurogenesis and the decreasing of the T cell-mediated inflammatory process were the two main molecular mechanisms activated in the brains of NDHSs underwent HPA. From our results, it is possible to conclude that, in elderly subjects, the transcriptional profile of CNS cells changes as a function of the PA conducted during life. Performing PA periodically supports the maintenance of the physiological balance of neuronal cells and, consequently, improves the quality of life of the elderly.