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

Life

Bin Zhang¹  MirandaE. Orr²  Eric Sah²  Sudarshan Krishnamurthy²  MohamedY. Ahmidouch²  GregoryJ. Gillispie² 

[1] Department of Genetics and Genomic Sciences, Department of Pharmacological Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston‐Salem, NC 27157, USA;

关键词: cellular senescence;    Alzheimer’s disease;    biology of aging;    neurodegeneration;    brain;    geroscience;   

DOI  :  10.3390/life11020153

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown