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Updated: Dec 13, 2025
Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
Published on: October 18, 2016
Aging and sex: Impact on microglia phagocytosis
Natalia Yanguas-Casás1,2, Andrea Crespo-Castrillo1, Maria-Angeles Arevalo1,2
1Consejo Superior de Investigaciones Científicas (CSIC), Instituto Cajal, Madrid, Spain.
Abstract:
Microglia dysfunction and activation are important hallmarks of the aging brain and are concomitant with age-related neurodegeneration and cognitive decline. Age-associated changes in microglia migration and phagocytic capacity result in maladaptive responses, chronic neuroinflammation, and worsened outcomes in neurodegenerative disorders. Given the sex bias in the incidence, prevalence, and therapy response of most neurological disorders, we have here examined whether the phagocytic activity of aged microglia is different in males and females. With this aim, the phagocytosis activity of male and female cells was compared in an in vitro aged microglia model and in microglia isolated from adult (5-month-old) or aged (18-month-old) mice. In both models, the phagocytosis of neural debris increased with aging in male and female cells and was higher in aged female microglia than in aged male cells. However, female aged microglia lost its ability to adapt its phagocytic activity to inflammatory conditions. These findings suggest that microglia phagocytosis of neural debris may represent a previously unexplored neuroprotective characteristic of aged microglia that may contribute to the generation of sex differences in the manifestation of neurodegenerative diseases.
Insights
Aging microglia show altered phagocytosis, with females clearing more neural debris but losing adaptability. This sex difference may impact neurodegenerative disease development.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia dysfunction is central to brain aging, neurodegeneration, and cognitive decline.
- Age-related changes in microglia contribute to chronic neuroinflammation and poorer neurological outcomes.
- Neurological disorders exhibit significant sex biases in incidence, prevalence, and treatment response.
Purpose of the Study:
- To investigate sex-based differences in the phagocytic activity of aged microglia.
- To compare phagocytosis in male and female microglia across different age groups and conditions.
Main Methods:
- Utilized an in vitro aged microglia model.
- Isolated and analyzed microglia from adult (5-month-old) and aged (18-month-old) male and female mice.
- Assessed the phagocytosis of neural debris under basal and inflammatory conditions.
Main Results:
- Phagocytosis of neural debris increased with aging in both male and female microglia.
- Aged female microglia exhibited higher phagocytosis of neural debris compared to aged male microglia.
- Aged female microglia demonstrated a reduced ability to adapt phagocytic activity in response to inflammatory stimuli.
Conclusions:
- Microglia phagocytosis of neural debris is an age-dependent process with distinct sex differences.
- Enhanced phagocytosis in aged female microglia may represent a neuroprotective mechanism.
- These sex-specific phagocytic characteristics could contribute to observed differences in neurodegenerative disease manifestation.
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