Cellular senescence in ischemic stroke: Cell-type specificity, temporal dynamics, and response to therapeutic...

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• Stroke triggers cellular programs resembling senescence and the senescence-associated secretory phenotype (SASP).
• Distinguishing true senescence from acute stress responses in injured brain tissue is challenging due to overlapping features.
• Existing research lacks a unified, cell-type-resolved framework across different stroke phases.

Purpose of the Study:

• To synthesize current literature on post-stroke senescence using a cell-type-resolved framework.
• To conceptualize post-stroke senescence-associated biology as a dynamic continuum rather than a binary state.
• To discuss translational implications of targeting senescence after stroke.

Main Methods:

• Literature synthesis using a cell-type-resolved framework.
• Analysis across acute, subacute, and chronic stroke phases.
• Examination of neurovascular and immune compartments.

Main Results:

• Post-stroke senescence is presented as a dynamic continuum where stress engages multiple senescence-related domains.
• Only a subset of these domains may stabilize into durable cell senescence.
• Convergent multi-domain evidence with spatial and cell identity resolution is emphasized.

Conclusions:

• Cautious use of the term "senescence-like" is advised during early injury.
• Modulating maladaptive secretory outputs may be more beneficial than cell elimination in early post-stroke windows.
• Key uncertainties include blood-brain barrier dynamics, risks of hemorrhage/infection, and interference with repair for senescence-targeting strategies.