Cellular senescence in skeletal muscle regeneration

Area of Science:

• Muscle Biology
• Cellular Aging
• Regenerative Medicine

Background:

• Skeletal muscle regeneration relies on muscle stem cells and a dynamic niche.
• Cellular senescence, a state of stable cell-cycle arrest, paradoxically influences this process.
• The senescence-associated secretory phenotype (SASP) from senescent cells impacts the regenerative microenvironment.

Purpose of the Study:

• To synthesize the complex and contradictory roles of cellular senescence in skeletal muscle regeneration.
• To differentiate between beneficial transient senescence and detrimental persistent senescence.
• To emphasize cell-type-specific contributions and the need for precise characterization of senescent cell dynamics.

Main Methods:

• Literature review and synthesis of existing research on cellular senescence and muscle regeneration.
• Analysis of studies investigating the impact of transient versus persistent senescence in various muscle injury models.
• Examination of cell-type-specific roles of senescent cells, including fibro-adipogenic progenitors (FAPs) and macrophages.

Main Results:

• Transient senescence in niche cells (e.g., FAPs, macrophages) supports acute muscle regeneration by promoting plasticity, differentiation, and debris clearance via SASP.
• Persistent senescence, particularly in aged or dystrophic muscle, can impair regeneration by creating a pro-inflammatory and pro-fibrotic niche.
• Conflicting findings highlight the context-dependent and cell-type-specific nature of senescence's effects.

Conclusions:

• Cellular senescence is a critical regulator of skeletal muscle regeneration with both beneficial and detrimental effects.
• Distinguishing between transient and persistent senescence is crucial for understanding its impact.
• Targeted senotherapeutic strategies are needed to harness beneficial senescence and mitigate detrimental effects for treating muscle aging and degenerative diseases.