Chemically Induced Senescence Prompts Functional Changes in Human Microglia-Like Cells

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Cellular senescence, characterized by cell cycle arrest and SASP, contributes to aging and neuroinflammation.
• Microglia, the primary immune cells in the CNS, are susceptible to senescence and play a role in brain aging.
• Current understanding of human microglia aging is limited due to challenges in accessing primary cells and adequate aging models.

Purpose of the Study:

• To investigate the impact of cellular senescence on human microglia.
• To establish a model for studying age-related changes in human microglia.
• To explore the functional consequences of senescence in microglia.

Main Methods:

• Chemically induced senescence in a human immortalized microglia cell line using a cocktail of senescence-inducing molecules.
• Assessed proinflammatory phenotype, phagocytic activity, and calcium signaling in senescent microglia.

Main Results:

• Chemically induced senescent microglia displayed a proinflammatory phenotype.
• Phagocytic activity was reduced in senescent microglia.
• Impaired calcium activity was observed in senescent microglia.

Conclusions:

• Chemically induced senescence effectively models key features of cellular aging in human microglia.
• Senescent microglia exhibit detrimental functional changes relevant to brain aging and neuroinflammation.
• This model provides valuable insights into the role of cellular senescence in human microglia aging.