Aged murine bone marrow myeloid and mesenchymal cells develop unique senescence phenotypes

Area of Science:

• Immunology
• Cell Biology
• Gerontology

Background:

• Cellular senescence, a state of irreversible cell cycle arrest, is a hallmark of aging.
• Senescence is primarily characterized in mesenchymal cells, but immune cell senescence phenotypes (senotypes) remain poorly understood.
• Investigating immune cell senotypes is crucial for understanding aging processes and age-related diseases.

Purpose of the Study:

• To investigate the senotype of immune cells in the bone marrow of aging mice.
• To compare the senescence phenotype of myeloid-lineage cells with mesenchymal cells.
• To evaluate the therapeutic potential of senolytics targeting senescent immune cells.

Main Methods:

• Single-cell approaches were used to analyze immune cell senescence.
• Global and cell-specific genetic senolytic mouse models were employed.
• Senescence markers, including p16 and senescence-associated secretory phenotype (SASP) markers, were assessed.

Main Results:

• Myeloid-lineage cells exhibited the highest expression of p16 and SASP markers among immune cells.
• Targeted clearance of p16+ myeloid cells had minor effects on age-related bone loss in male mice and no effect in females.
• p16+ myeloid cells were rapidly cleared and repopulated, leading to a lack of sustained reduction in senescent cell burden.

Conclusions:

• Aged bone marrow myeloid cells display a distinct senotype that differs from mesenchymal cells.
• The senescence phenotype in myeloid cells may not fully develop as described in mesenchymal cells.
• Further characterization of immune cell senotypes across different tissues is warranted.