Research on Peripheral Nerve Aging and Degeneration: Cellular Changes and Mechanism Exploration From the Perspective of Single‐Cell Sequencing

ABSTRACT As age increases, there are structural and functional alterations in the peripheral nervous system (PNS), significantly affecting movement, sensation and autonomic function. Understanding the characteristics and mechanisms of PNS aging is crucial for preventing and treating related diseases. This study employed single‐cell sequencing technology to analyse the dorsal root ganglia (DRG) and sciatic nerve (SN) of aging rats, in comparison with adult rats. The research investigated the mechanisms underlying PNS aging and degeneration, revealing the transcriptional profiles of various cell types. Significant differences were observed in the proportion of Schwann cells between the DRG and SN of adult and aged rats. The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) revealed that pathways related to neurodegeneration were upregulated in Schwann cells. Additionally, lipid metabolism pathways were upregulated in the SN of aged rats, suggesting that certain lipid signalling molecules may influence cell proliferation. Through further re‐clustering of myelinating Schwann cells, six distinct subtypes were identified. The anti‐aging protein protocadherin 9 (PCDH9) was preliminarily screened and found to be significantly downregulated with age. In vitro experiments confirmed that PCDH9 expression is associated with Schwann cell proliferation and differentiation. By using gene expression analysis and cell type across several age groups, this study offers important insights into the mechanisms of PNS aging and degeneration.