Single cell RNA-seq of young and aged whole lungs following IAV infection

We report analysis of lung single cell transcriptome in aged and young mice infected with influenza A virus (IAV) for 9 days. It represents Cd4+ T cells population in aged lung were substantially decreased. Moreover mTOR signaling pathway were downregulated in Cd4+ cluster of aged lungs. It implies that reduced Cd4+ T cell population during IAV infection in aged mice linked to disrupted mTOR signaling pathway. In contrast, Gene Ontology (GO) analysis of CD8+ T cells from young and aged mice revealed an upregulation of the p53 pathway in aged CD8+ T cells, suggesting increased DNA damage may further restrict their proliferative potential. Moreover, We report analysis of lung single cell transcriptome in metformintreated aged mice infected with influenza A virus (IAV) for 9 days. Gene set enrichment analysis of Cd4+ and Cd8+ T cells revealed that metformin treatment positively enriched E2F targets, type I interferon (IFN α) response, and oxidative phosphorylation pathways. These findings suggest that metformin improves age associated T cell dysfunction by reducing inhibitory signaling and DNA damage, while enhancing mitochondrial metabolism, E2F and interferon signaling, thereby improving T cell proliferation, function, and viral clearance in aged hosts.