About
Cellular senescence is classically viewed as a stress response that enforces stable cell-cycle arrest, produces a pro-inflammatory secretory phenotype (SASP), and resists apoptosis. While pathological accumulation of senescent cells drives fibrosis, aging, and cancer, their clearance can delay age-related decline. Yet senescence is not only detrimental, it also positively contributes to embryonic development, limits fibrosis, and promotes tissue repair. How senescent cells achieve these context-dependent beneficial roles remains largely unknown.
Pregnancy and postpartum represent unique physiological windows that remodel multiple organs. In the mammary gland, postpartum involution is a striking example: epithelial structures generated during pregnancy collapse, tissue undergoes profound remodeling and inflammation, and remarkably, the gland is restored without scar formation and ready for the next reproductive cycle. Involution has been proposed as a model of scar-less wound healing, but its regulatory mechanisms are poorly understood. Importantly, dysregulated involution is linked to postpartum breast cancer, a particularly aggressive and understudied breast cancer subgroup.
Interestingly, we found that senescence is induced during postpartum mammary gland involution. Our findings reveal a dual role for senescence in postpartum involution: essential for physiological tissue remodelling yet exploitable by cancer. This establishes a critical link between physiological senescence and tumour progression, providing new insights into how senescence contributes to cancer in an age- and context-dependent manner https://doi.org/10.1101/2024.12.29.630686.
This opens up several fundamental questions:
- What are the molecular programs that define involution-induced senescence?
- What are the signals trigger involution-induced senescence?
- How do senescent cells orchestrate tissue remodeling?
- What are the systemic and long-term consequences of IIS for regeneration, fibrosis, and cancer risk?
