A new review published in Volume 18 of Aging on May 30, 2026, examines the relationship between cellular senescence and stemness.
Led by Angelos Papaspyropoulos and Vassilis G. Gorgoulis from the National and Kapodistrian University of Athens and the Biomedical Research Foundation of the Academy of Athens, Greece, the review explores the complex, context-dependent interaction between two fundamental biological processes.
Cellular senescence is a permanent cell cycle arrest in response to stress, while stemness refers to the ability of stem cells to self-renew and differentiate. The review summarizes evidence that their interaction can be either antagonistic or cooperative.
Key Findings
Under normal physiological conditions, senescence can limit stem cell activity, impairing regeneration in mesenchymal stem cells, muscle satellite cells, dental pulp stem cells, and pancreatic β-cell progenitors.
Reducing senescence in experimental models restored stem cell function and improved tissue regeneration.
"The interaction between senescence and stemness is context-dependent and can be either antagonistic or cooperative."
Molecular pathways involved include p53/p21, p16INK4A/RB, mTOR, Wnt/β-catenin, and the senescence-associated secretory phenotype (SASP).
In cancer, senescent cells can promote the emergence of cancer stem cells via SASP inflammatory signals or through escape from senescence. This has been reported in B-cell lymphoma, liver, colon, lung, and breast cancers.
Clinical Implications
- Eliminating senescent cells may improve tissue repair and reduce age-related diseases.
- Indiscriminate targeting of senescence could interfere with beneficial regenerative processes.
- The authors emphasize the need for evaluating senolytic therapies with validated biomarkers and clinical studies.
The review concludes that understanding the context-dependent relationship between senescence and stemness is important for developing regenerative therapies and cancer treatments.