International Business Department           Liu Bojia           Feburary 26, 2023

  Cells are the basic unit of structure and physiological function in our bodies, and animal cells rely on thin cell membranes to separate the interior of the cell from the external environment. As a result, cell membranes are frequently damaged by various external activities, such as mechanical forces generated by muscle or tissue contraction, or attack by pathogens.

  These damages pose a threat to the survival of the cell, so it is important to repair the damage in a timely manner. In the past, research has suggested that plasma membrane damage and repair can lead to two scenarios: one in which the damage is so severe that repair cannot be completed causing apoptosis or pyroptosis, a pattern that has actually been focused on by scientists for the development of cancer-related therapeutic strategies; and the other in which the damage is less severe, and the cells continue to perform their normal functions after repair is completed.

  In the recent Nature Aging, a sub-publication of Nature, scientists discovered a third possibility, when the damage is moderate, the cell membrane can achieve repair and avoid death, but the cell never goes back to a healthy state, but enters a state of senescence (aging). As with senescent cells that arise with age, senescence caused by plasma membrane damage causes the cell to lose its original function and release pro-inflammatory molecules into the periphery, resulting in tissue damage and the onset of broader senescence.

  Of course, the breakthrough of the new study is not limited to this. When studying plasma membrane damage in eukaryotic cells in the past, we still lacked a universal method for damage induction. Plasma membrane damage inducers used in mammalian cells, for example, hardly work in yeast, which possesses a cell wall, making it difficult for scientists to utilise this model organism, which is suitable for studying genetics.

  However, the authors found that while wild-type yeast survived when the medium contained low concentrations of sodium dodecyl sulfate (SDS), yeast with defective plasma membrane damage repair mechanisms died. This suggests to them that SDS may be able to induce plasma membrane damage in yeast.

  The new study verified this using a fluorescent molecule, which they should have been able to observe inside the yeast that survived in SDS-containing medium if plasma membrane damage was associated with SDS. The results were also as expected, with fluorescent molecules appearing in about 10 per cent of the yeast cells, suggesting that damage caused by SDS occasionally allows fluorescent molecules to penetrate, but that most yeast cells prevent the process by repairing the plasma membrane in time. If the plasma membrane repair mechanism of wild-type yeast is artificially disrupted, fluorescent molecules are detected in about 75% of the cells.

  In addition to this, the authors also demonstrated that SDS is capable of disrupting cell walls and forming localised damage. And SDS can also induce plasma membrane damage in human cells.

  However, contrary to expectations, the plasma membrane damage induced by appropriate concentrations of SDS did not kill wild-type yeast, but unexpectedly shortened their lifespan, as well as mechanical force-induced damage. In human fibroblasts, SDS-induced plasma membrane damage caused cellular senescence, and the higher the concentration of SDS, the slower the cell proliferation. Mechanistically, plasma membrane damage caused a rapid increase in the level of p53 protein, which may directly inhibit cell proliferation and trigger the onset of cellular senescence.

  Study corresponding author Professor Keiko Kono said, " In a sense, cell membrane damage changes the fate of the cell. " And this subtype of senescent cells identified in the new study - plasma membrane damage-dependent senescent cells - may have been overlooked in the past. Now this discovery will contribute to future research on aging-related mechanisms as well as life-extension strategies.