Staphylococcus aureus phagocytosis is affected by senescence

Area of Science:

• Cellular senescence
• Immunology
• Aging research

Background:

• Senescent cells accumulate with age, leading to organ dysfunction and increased susceptibility to infections.
• The underlying mechanisms, particularly concerning immune cell function, remain incompletely understood.

Purpose of the Study:

• To investigate the impact of cellular senescence on the endophagocytic pathway and bacterial clearance.
• To determine if senescent cells exhibit altered bacterial uptake and intracellular processing.

Main Methods:

• Confocal microscopy to analyze endocytic vesicle populations and bacterial internalization.
• Western blot assays to assess vesicle maturation and degradation.
• Infection assays with *Staphylococcus aureus* in senescent and control cells, including experiments with endophagosomal maturation inhibitors.
• Analysis of bone marrow-derived macrophages (BMDMs) from aged animals.

Main Results:

• Senescent cells showed an increased number of vacuoles, partly due to larger cell size, but normal vesicle maturation and degradation.
• A significant decrease in the intracellular recovery of *Staphylococcus aureus* was observed in senescent cells.
• Bacterial adherence and internalization were reduced in senescent cells, confirmed by microscopy.
• Similar defects in bacterial clearance were found in BMDMs from aged animals.

Conclusions:

• Cellular senescence impairs the ability of immune cells to internalize bacteria, specifically affecting adherence and uptake.
• This diminished bacterial clearance by senescent cells contributes to increased susceptibility to severe infections in the elderly.