Damage to cell membranes causes cell aging, finds new study

Our cells are surrounded by a delicate membrane that is only 5 nanometers thick, 1/20 of a soap bubble. Cells are easily damaged by physical activity, including muscle contractions and tissue injury. To cope with such damage, cells are equipped with mechanisms that can repair membrane damage to a certain extent.

Mechanical damage to Cell membrane It was previously thought to trigger two simple cellular outcomes: regeneration or death. However, in a new study, researchers have discovered a third result.Cellular senescence. The task appears in Nature Aging.

“When I started this project, I only wanted to understand the mechanism of membrane repair in damaged cells,” recalls Professor Keiko Kono, head of the Okinawa Institute of Science and Technology Membranology Unit and senior author of the study. was.” Unit, including Kojiro Soda, Yohsuke Moriyama, Noorhani Razali and co. “Unexpectedly, we discovered that damage to the cell membrane, in a sense, changes the fate of the cell.”

The key to determining cell fate is the extent of damage and the resulting influx of calcium ions. Damage to the thin cell membrane can be easily repaired, allowing cells to continue cell division without problems. Higher levels of cell membrane damage induce cell death. However, moderate levels of cell membrane damage convert cells to senescent cells after several days, although membrane resealing appears to be successful.

Cancer cells divide indefinitely. In contrast, normal non-cancerous cells have a limited capacity for cell division—about 50 times the first division ceases irreversibly, and cells enter a state known as cellular senescence. Senescent cells are still metabolically active, but unlike young ones Healthy cells, they produce various secreted proteins that enhance immune responses in both nearby tissues and distant organs. These mechanisms can induce both beneficial and harmful changes in our bodies, including accelerated wound healing, cancer promotion, and aging.

Over the past decade, several studies have shown that senescent cells are present in the bodies of animals, including humans, and that removing senescent cells restored body functions in experimental animals. can go. However, the cause of cell senescence in the human body remains a controversial topic.

“Give Gene expression profile And bioinformatics suggested that cell membrane damage explains the origin of senescent cells in our bodies, especially those close to damaged tissues,” explains Professor Kuno.

The best established inducer of cellular senescence is repeat. Cell division. Many other stresses also induce cellular senescence in the laboratory setting, such as DNA damage, oncogene activation, and epigenetic changes. A long-standing belief in the research field was that various stresses ultimately induce cellular senescence by activating the DNA damage response.

However, the authors revealed that cell membrane damage induces cellular senescence through a different mechanism involving calcium ions and the tumor suppressor gene p53. These findings may help in developing strategies to achieve healthy longevity in the future.