Single-nucleus transcriptomic profiling identifies cell types and their age-associated transcriptional changes in the glia-rich optic nerve of the African turquoise killifish

The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for aging studies, displaying rapid aging phenotypes within its four to six-month lifespan. Previous transcriptomic profiling of the aging killifish retina suggested that CNS immune and glial cells undergo more pronounced age-associated transcriptomic changes than neurons.

Given the heterogeneous responses of CNS immune and glial cells to aging, we performed snRNAseq on optic nerves from young-adult (6-week-old) and aged (18-week-old) killifish. Our findings demonstrate that all expected CNS immune and glial populations are present in the optic nerve and undergo distinct aging-associated transcriptional changes. Oligodendroglia, however, displayed the most pronounced alterations, including a marked induction of IFN-associated pathways and decrease in lipid metabolism, indicating that oligodendroglial are the major agign cell population.