Microglia in Brain Aging and Age-Related Diseases: Friends or Foes?

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Population aging presents challenges for preventing age-related neurodegenerative diseases and cognitive frailty.
• Chronic neuroinflammation and impaired cellular debris clearance, regulated by microglia, are linked to aging and neurodegeneration.
• Aging impairs microglial function, leading to reduced surveillance, phagocytosis, and a proinflammatory state, exacerbating neural damage.

Purpose of the Study:

• To review microglial changes in aging, frailty, and neurodegeneration.
• To emphasize the dual roles of microglia in brain health and disease.
• To discuss strategies for modulating microglial function to maintain brain health and prevent age-related conditions.

Main Methods:

• Review of current evidence on microglial changes.
• Analysis of single-cell transcriptomic studies identifying distinct microglial subsets.
• Emphasis on the functional consequences of microglial alterations in aging and disease.

Main Results:

• Aging microglia exhibit reduced surveillance, motility, and phagocytic efficiency, adopting a proinflammatory state.
• Distinct microglial subsets, like CD11c+ microglia, show protective features including enhanced debris clearance and neurotrophic factor expression.
• Even protective microglial phenotypes can become detrimental under chronic inflammation or pathological conditions.

Conclusions:

• Microglia play a critical dual role in brain aging, frailty, and neurodegeneration.
• Modulating microglial function offers potential therapeutic strategies for maintaining brain health.
• Targeting microglial pathways may be key to preventing and treating age-related cognitive decline and neurodegenerative diseases.