Fig. 2. Alterations of immune cell populations in ageing.

Single-cell techniques identified expanded and reduced immune cell populations with distinct phenotypes in multiple organs of old mice. Exhausted PD1⁺TOX⁺CD8⁺ T cells and activated PD1⁺CD4⁺ T cells accumulate across multiple tissues in ageing, whereas natural killer (NK) cells and innate lymphoid cells (ILCs) are among the cell subsets that are reduced in abundance in various organs. Functionally and phenotypically similar CD38⁺ macrophages expand in metabolically active organs — liver and fat — of old mice^173,174. Unlike these cell subsets commonly affected by age in many tissues, alterations of other immune cell populations show organ-specific patterns in ageing. For example, activated regulatory T cells (T_reg cells) increase in abundance in the spleen of old mice^25,69,154. Tissue-resident alveolar macrophages decrease in abundance and fibronectin 1-positive (FN1⁺), CC-chemokine receptor 2-positive (CCR2⁺) interstitial macrophages increase in abundance in the lungs of old mice^25,150. Distinct subsets of age-associated B cells accumulate in the spleen (B cells expressing Zbtb32, Apoe and Tbx21) and peritoneal cavity (B1 cells expressing Zcwpw1 and Ctla4) of aged mice. cDC1, conventional type 1 dendritic cell; ICAM1, intercellular adhesion molecule 1; ILC1s, group 1 innate lymphoid cells; ILC2s, group 2 innate lymphoid cells.