Genome-Wide Network Analysis of DRG-Sciatic Nerve Network-Inferred Cellular Senescence and Senescence Phenotype in Peripheral Sensory Neurons
Year: 2024
Type: article
Abstract: Accumulation of senescent neurons in the dorsal root ganglion (DRG) is an important tissue phenotype that causes age-related degeneration of peripheral sensory nerves. Senescent neurons are neurons with arrested cell cycle that have undergone cellular senescence but remain in the tissue and play various biological roles. To understand the accumulation of senescent neurons in the DRG during aging, we aimed to elucidate the mechanism that induces cellular senescence in DRG neurons and the role of senescent DRG neurons. We integrated multiple public transcriptome datasets for DRGs, which represent cell bodies in neurons, and sciatic nerve, which represents axon in neurons, using network medicine-based bioinformatics analysis to account for axon-cell body interaction involved in cellular senescenc. Network medicine-based bioinformatics analysis revealed that age-related Mapk3 decline leads to impaired cholesterol metabolism and biosynthetic function in axons, resulting in compensatory upregulation of Srebf1, a transcription factor involved in lipid and cholesterol metabolism, which in turn leads to CDKN2A-mediated cellular senescence. Furthermore, this analysis revealed that senescent DRG neurons develop a senescence phenotype characterized by activation of antigen-presenting cells via upregulation of Ctss as a hub gene. B cells inferred as antigen-presenting cells activated by Ctss, and CD8-positive T cells inferred as cells that receive antigen presentation from the B cells.
Source: Molecular Neurobiology
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4405701077