Analysing the Mechanisms of Aging in the Human Brain Through Single Cell Isolation and Multi-omic Analysis

Aging in the brain refers to the gradual loss of physiological and biochemical functions, leading to cognitive decline and neurodegeneration. Aging is a natural process, but its progression can be accelerated by primary causes such as genetic predisposition, inflammation, and protein misfolding, and secondary influences like poor lifestyle choices, chronic stress, toxins, pollutants, and neurodegenerative diseases. Genomic instability, a byproduct of aging, is triggered by both primary and secondary causes. In order to investigate the cellular consequences of such instability, we performed single-cell isolation of different human brain samples of different age groups and conducted multi-omics analyses. Our experiments identified different types of neuronal cell types and states affected or involved by aging, with astrocytes standing out among the chromatin clusters. Biochemical pathway analysis of astrocytes and other cells involved, such as oligodendrocytes, intratelencephalic neurons, and microglia cells, revealed age-related biochemical changes, including both upregulated and downregulated pathways. We found the MYC, and transcription regulator is an upstream-activated regulator to many adverse age-related effects, such as RNA repression and neuron apoptosis. These findings contribute to medical research, molecular biology, and bioinformatics, with the potential to guide the creation of treatments to counteract cognitive decline and neurodegenerative disease.