Aging and sex: Impact on microglia phagocytosis

• Published in: Aging cell 2020-08, Vol.19 (8), p.e13182-n/a
• Main Authors: Yanguas‐Casás, Natalia, Crespo‐Castrillo, Andrea, Arevalo, Maria‐Angeles, Garcia‐Segura, Luis Miguel
• Format: Article
• Language: English
• Subjects: Aging; Analysis; Animal models; Brain; Cognitive ability; Cytokines; dysfunction; E coli; Females; Gender differences; Genotype & phenotype; Inflammation; irresponsiveness; Microglia; Nervous system diseases; Neurodegeneration; Neurodegenerative diseases; neuroinflammation; Neurological diseases; Neurological disorders; Neuroprotection; Original; Pathogens; Phagocytes; Phagocytosis; Senescence; Sex; Sex differences; Sex discrimination; Sexes; Tumor necrosis factor-TNF
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13182

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. Sex differences in postnatal microglia: higher pathogen‐specific phagocytosis is detected in male cells while females show an enhanced nonspecific and neural debris phagocytosis compared to the other sex. Phagocytosis of neural debris increased with aging in male and female cells. These characteristics of the phagocytic behaviour of microglia are potential contributors to the generation of sex differences in the manifestation of neurodegenerative diseases.