A new study has found that mechanical damage to the cell membrane in human cells can trigger cellular senescence
Our cells are surrounded by a fragile membrane that is only 5 nanometers thick, one-twentieth the thickness of a soap bubble. Physiological activities such as muscle contractions and tissue injuries easily damage cells. To cope with this damage, cells are equipped with mechanisms that can repair membrane damage to some extent.
Previously, it was assumed that mechanical damage to the cell membrane triggers two simple cellular consequences: recovery or death. However, in this study, researchers discovered a third finding: cellular aging.
“When I started this project, my goal was simply to understand the repair mechanisms of damaged cell membranes,” recalls Professor Keiko Kono, head of the Membranology Department and lead author of this study. “Unexpectedly, we discovered that damage to the cell membrane somehow changes the fate of the cells.”
The key to determining cell fate is the extent of damage and the subsequent influx of calcium ions. Subtle damage to the cell membrane can be easily repaired, allowing cells to continue dividing smoothly. The greatest damage to the cell membrane leads to cell death. However, with moderate damage to the cell membrane, the cells become senescent cells a few days later, even if the resealing of the membrane appears to be successful.
Cells are not immortal
Cancer cells divide indefinitely. In contrast, normal, noncancerous cells have a limited ability to divide: about 50 times before division stops irreversibly and the cells enter a state known as cellular senescence. Senescent cells remain metabolically active but, unlike young, healthy cells, produce various secretory proteins that enhance the immune response in both nearby tissues and distant organs. This mechanism can cause positive and harmful changes in our body, such as: B. Accelerating wound healing, promoting cancer and aging.
Over the last decade, numerous studies have reported the existence of senescent cells in the bodies of animals, including humans, and that removal of senescent cells can restore body functions in laboratory animals. However, the cause of cell aging in the human body remains a controversial topic. “Gene expression profiling and bioinformatics suggested that damage to the cell membrane explains the origin of senescent cells in our body, particularly those located near damaged tissue,” explains Professor Kono.
The best established trigger of cellular senescence is repeated cell division. Many other stressors also induce cellular senescence in the laboratory, such as DNA damage, oncogene activation, and epigenetic changes. For a long time, the dogma in research was that various types of stress ultimately induce cell senescence by activating the DNA damage response. However, the authors discovered that cell membrane damage induces cell senescence through a different mechanism involving calcium ions and the tumor suppressor gene p53. These findings can help develop a strategy to achieve healthy longevity in the future.
REFERENCE
Damage to the plasma membrane limits replication lifespan in yeast and induces premature senescence in human fibroblasts