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Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types
Taylor Russo1,2, Markus Riessland1,2
1Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, USA.
Aging Cell
|August 15, 2026
Summary
Cellular senescence spreads through the brain via the senescence-associated secretory phenotype (SASP). Researchers identified specific SASP targets that could be therapeutically modulated to treat age-related brain dysfunction and neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Cellular senescence, characterized by the senescence-associated secretory phenotype (SASP), can propagate senescence in neighboring cells.
- The SASP influences immune cell recruitment and is linked to age-related neurodegenerative conditions and brain inflammation.
- Understanding cell-type-specific SASP and senescence spreading in the brain is crucial.
Purpose of the Study:
- To profile cell-type-specific SASP features in the brain.
- To characterize the directionality of paracrine senescence spreading between major brain cell types.
- To identify therapeutic targets for modulating senescence spreading in the brain.
Main Methods:
- Profiling of cell-type-specific SASP.
- Characterization of paracrine senescence spreading directionality.
- Identification of SASP ligand-receptor pairs.
- Inhibition of selected SASP factors.
Main Results:
- Identified key SASP ligand-receptor pairs driving paracrine senescence dissemination in the brain.
- Demonstrated that targeting specific SASP factors can ameliorate senescence spreading in a cell-type-dependent manner.
- Provided insights into the SASP-dependent reaction of immune cells and age-related tissue dysfunction.
Conclusions:
- Specific SASP targets were identified for therapeutic intervention in human brain cells.
- Findings inform potential strategies for addressing normal aging and neurodegenerative diseases.
- The study highlights the role of SASP in cell-type-specific senescence spreading and its implications for brain health.
