The Hidden Link Between Cell Membrane Damage and Cellular Senescence Revealed

Researchers from the Okinawa Institute of Science and Technology (OIST) and researchers from University of Tokyo, Nagoya University, and Nagoya City University, found that disruption to the cell membrane accelerates cellular senescence or cell aging.

The story was published in the journal Nature Aging.

The thin membrane that encircles the cells is barely 5 nm thick, 1/20 of the thickness of a soap bubble. Physiological activity such as muscular contraction and tissue injury can easily destroy cells. Cells have mechanisms built in to heal some degree of membrane damage to deal with such damage.

It was often thought that mechanical injury to the cell membrane resulted in one of two straightforward biological outcomes: recuperation or death. Cellular senescence, however, was the third result the researchers found in their investigation.

When I started this project, I simply aimed to understand the repair mechanisms of the damaged cell membrane, and unexpectedly, we ended up discovering that cell membrane damage, in a sense, switches cell fate.”

Keiko Kono, Study Senior Author, Professor, and Head, Membranology Unit, Okinawa Institute of Science and Technology

Professor Keiko Kono headed the Unit at OIST, which involved multiple members from the unit, including Kojiro Suda, Yohsuke Moriyama, Nurhanani Razali, and colleagues.

The degree of damage and the following influx of calcium ions are critical in deciding the destiny of the cells. The damage to the thin cell membrane can be readily repaired, enabling the cells to divide without any issues.

Cell death is induced by the highest degree of damage to the cell membrane. Even if membrane resealing appears to be successful, a moderate degree of cell membrane damage causes the cells to become senescent cells several days later.

Cancer cells proliferate indefinitely. On the other hand, normal, non-cancerous cells have a limited ability to divide; they can only do so up to 50 times before division is irrevocably halted, and they enter a condition called cellular senescence.

Even though they still have a metabolism, senescent cells secrete different proteins that trigger immunological responses in neighboring tissues and distant organs. This is in contrast to youthful, healthy cells.

This process can cause both positive and negative changes in human bodies, such as aging, the promotion of cancer, and the acceleration of wound healing. Numerous investigations conducted over the past ten years have revealed the existence of senescent cells in animal bodies, including human bodies.

And the ability to restore bodily functioning in experimental animals by removing these cells. However, the reason behind the human body's cellular senescence is still unknown.

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.”

Keiko Kono, Study Senior Author, Professor, and Head, Membranology Unit, Okinawa Institute of Science and Technology

Repeated cell division is the most well-established inducer of cellular senescence. In a lab setting, a variety of other stressors, including DNA damage, oncogene activation, and epigenetic modifications, also cause cellular senescence.

In the realm of science, it has long been accepted wisdom that different stimuli eventually cause cellular senescence by triggering the DNA damage response.

The authors did discover, however, that a distinct mechanism involving calcium ions and the tumor suppressor gene p53 causes cellular senescence in response to damage to the cell membrane. These results could aid in the formulation of a plan for future healthy longevity.