Evidence of the Cellular Senescence Stress Response in Mitotically Active Brain Cells-Implications for Cancer and Neurodegeneration

Cellular stress responses influence cell fate decisions. Apoptosis and proliferation represent opposing reactions to cellular stress or damage and may influence distinct health outcomes. Clinical and epidemiological studies consistently report inverse comorbidities between age-associated neurodegenerative diseases and cancer. This review discusses how one particular stress response, cellular senescence, may contribute to this inverse correlation. In mitotically competent cells, senescence is favorable over uncontrolled proliferation, i.e., cancer. However, senescent cells notoriously secrete deleterious molecules that drive disease, dysfunction and degeneration in surrounding tissue. In recent years, senescent cells have emerged as unexpected mediators of neurodegenerative diseases. The present review uses pre-defined criteria to evaluate evidence of cellular senescence in mitotically competent brain cells, highlights the discovery of novel molecular regulators and discusses how this single cell fate decision impacts cancer and degeneration in the brain. We also underscore methodological considerations required to appropriately evaluate the cellular senescence stress response in the brain.

Automated summary

Cellular stress responses play a crucial role in cell fate decisions, with apoptosis and proliferation representing distinct reactions to stress or damage. Studies have shown an inverse relationship between age-related neurodegenerative diseases and cancer, with cellular senescence potentially contributing to this correlation. Senescent cells, while beneficial in preventing cancer in mitotically competent cells, can also secrete harmful molecules that contribute to disease and dysfunction in surrounding tissues, emerging as mediators of neurodegenerative diseases in recent years.