Single-cell analysis of human peripheral blood reveals high immune response activity in successful ageing individuals

Beneficial remodeling of the immune system in successful ageing individuals (centenarians and supercentenarians) is critical for healthy ageing. However, mechanisms for dynamic regulation of immunity during ageing remain unclear. We use single-cell RNA sequencing (scRNA-seq) as an analytical strategy to study the dynamic regulation of immunity during aging and its molecular mechanisms at the single-cell level. We performed an integrative analysis of 87,215 peripheral blood mononuclear cells, from seven supercentenarians, three centenarians, and four elderly controls, generated by single-cell transcriptomics complemented with fluorescence-activated cell sorting. Animals experiments were also conducted to validate the makers of healthy aging found by our bioinformatic analysis and further explore the dynamic of immune changes during aging process. We found that CD8⁺ effector memory T cells and terminally differentiated B cells were enriched in the longevity group (centenarians and supercentenarians), whereas naïve T cells and Tregs were enriched in elderly controls. CD56^dim NK cells in the longevity group activated Fc-γ receptor signaling. The higher antigen-presenting ability of CD14⁺ monocytes in the longevity group and the CellChat analysis indicated that CD14⁺ monocytes might assist active T and B cells. Here, we revealed the adaptive immune remodeling geromarkers of immunosenescence in centenarians and supercentenarians, which could be considered as biomarkers of healthy aging, and might help sustain immune responses and achieve exceptional longevity.