Aged bone marrow myeloid and mesenchymal cells develop unique senescence phenotypes

Cellular senescence was originally characterized in mesenchymal cells and subsequently this concept was extended to immune cells. However, the extent to which immune cells differ from mesenchymal cells in their senescence phenotype, or “senotype”, is unclear. Here, we evaluated the senotypes of bone marrow/bone immune versus mesenchymal cells. Among immune cells, myeloid cells exhibited the highest expression of p16. However, targeted clearance of p16+ myeloid cells using LysM-Cre x p16-LOX-ATTAC mice only had minor effects on age-related bone loss in male mice, with no effects in females. After clearance, p16+ myeloid cells were only transiently reduced, unlike when targeting p16+ mesenchymal cells. In the same bones, aged myeloid cells demonstrated lower expression of senescence markers than mesenchymal cells and, when induced in culture, the senescence phenotype of myeloid cells differed substantially from that of mesenchymal cells. Our findings indicate that aged bone marrow myeloid cells do not achieve the fully developed senescent phenotype originally described in mesenchymal cells, justifying further characterization of senotypes of immune cells across tissues. Overall design: The purpose of this particular bulk RNAseq study is to compare the transcriptomes of AP20187 (AP) versus Vehicle in the spleen, flushed diaphysis, inguinal fat and quadricepts of male, 24 month old p16-LOX-ATTAC mice crossed with the LysM-Cre mosue driver.