New insights into aging microglia and their link to neurological disorders
Researchers at the Institute of Environmental Medicine, Karolinska Institutet have taken an important step toward understanding how microglia, the brain's immune cells, change with age and how these changes may contribute to age-related neurological diseases.
Using a novel method of long-term cultivation in a controlled environment, scientists were able to study the effects of aging on microglia without external interference.
The study revealed that aged microglia exhibit altered gene expression and a weakened immune response compared to their younger counterparts. While both young and aged microglia respond to inflammation, the intensity of the response is significantly reduced in older cells. This suggests a diminished capacity to address threats in the brain, potentially contributing to conditions like Alzheimer’s, Parkinson’s diseases or adult brain tumors.
The researchers identified 13 key genes that could serve as markers of microglial aging, including SLC16A3 and P2RY13, which showed consistent changes in both mouse and human brains from aged individuals. These findings enhance our understanding of how microglia are affected by aging and pave the way for future therapies to slow down or reprogram these changes.
“Aging is a widely recognized risk factor for numerous brain diseases, including neurodegenerative disorders and brain tumors”, said Martin Škandík, lead researcher of the study and researcher at the Institute of Environmental Medicine. “Our findings reveal that aging significantly alters microglia, the resident immune cells of the brain, impairing their ability to respond effectively and protect the brain from challenges. This discovery is of interest for our understanding of how these brain diseases develop and identifying potential strategies to combat them.”
The study also highlights the importance of developing better models to study aging processes and brings hope for new breakthroughs in the fight against age-related diseases.
Publication
Age-associated microglial transcriptome leads to diminished immunogenicity and dysregulation of MCT4 and P2RY12/P2RY13 related functions. Škandík M, Friess L, Vázquez-Cabrera G, Keane L, Grabert K, Cruz De Los Santos M, Posada-Pérez M, Baleviciute A, Cheray M, Joseph B. Cell Death Discov. 2025 Jan;11(1):16, doi: 10.1038/s41420-025-02295-1.