Our cells are surrounded by a fragile membrane that's only 5 nanometers thick, 1/20 of a soap bubble. Cells are easily damaged by physiological activities, including muscle contraction and tissue injury. To cope with such damage, cells are equipped with mechanisms that can repair membrane damage to a certain degree. Mechanical damage to the cell membrane was previously believed to trigger two simple cellular outcomes: recovery or death. In this study, however, the researchers uncovered a third outcome -- cellular senescence. When researchers started this project, they simply aimed to understand the repair mechanisms of damaged cell membrane. Unexpectedly, they ended up discovering that cell membrane damage, in a sense, switches cell fate.

 

The key to determining cell fate is the extent of damage and subsequent calcium ion influx. The thin cell membrane damage can be easily repaired, allowing the cells to continue cell division without any trouble. The highest level of cell membrane damage induces cell death. However, a middle level of cell membrane damage turns the cells into senescent cells several days later, even though membrane resealing seems successful. Cancer cells divide unlimitedly. In contrast, non-cancerous normal cells have a limited capacity for cell division -- around 50 times before division is irreversibly stopped, and the cells enter a state known as cellular senescence. The gene expression profile and bioinformatics suggested that cell membrane damage explains the origin of senescent cells in our bodies, specifically the ones near damaged tissues.

 

The best-established inducer of cellular senescence is repeated cell division. Many other stresses also induce cellular senescence in a laboratory setting, such as DNA damage, oncogene activation, and epigenetic changes. The long-standing dogma in the research field was that various stresses induce cellular senescence ultimately via the activation of DNA damage response. However, the authors uncovered that cell membrane damage induces cellular senescence via a different mechanism that involves calcium ions and the tumor suppressor gene p53. These findings may contribute to develop a strategy to achieve healthy longevity in the future.