Music compensates for altered gene expression in age-related cognitive disorders

Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n=60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD) as revealed by a multi-cohort study (n=1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders. Overall design: Music exerts a profound influence on human brains, affecting emotions, activating the reward system, and inducing changes in brain anatomy. However, research on the impact of music on gene expression is still in its nascent stages. The present study represents the first attempt to analyze the effect of music on the transcriptome of ACD patients. Capillary blood samples were collected from ACD patients and healthy donors using a minimally invasive procedure before and after a 50-minute session of classical musical stimuli in an ecologically valid environment. Subsequently, we performed RNA sequencing on these samples, allowing for the analysis of gene expression information for over 35,000 transcripts. The analysis focused on differential expression between the two time points and cohorts, as well as the contextualization of gene expression changes within the framework of genes and pathways that exhibit dysregulated expression in MCI and AD