On a crowded bus, people edge away from the passenger who has taken up too much room. Something similar happens in the body's tissues: when a senescent cell appears among normal cells, one that has stopped dividing but hasn't died, its neighbors start to crowd it. For the first time, scientists have shown that normal cells literally squeeze such a cell, compressing it until it dies.

The authors engineered cells in which they could switch on the production of proterin, a protein that triggers premature senescence. They seeded these cells alongside normal ones and watched. It turned out that cells with proterin die more often than ordinary ones. But only if they are pressed tightly against their neighbors. When cells were grown separately or next to cells with a disrupted protein that helps them stick together, the death rate dropped.

Using tiny beads embedded in the substrate, the scientists measured the forces that cells exert on the surface. It turned out that before a senescent cell dies, its neighbors press down on it. Inside the senescent cell, this pressure activates the JNK and p38-MAPK signaling pathways, which raise the level of the protein p53 and lower the level of the protein p21. p21 normally protects a cell from death, and its decline makes the cell vulnerable. When these pathways were blocked, the cells survived.

But not all senescent cells are equally sensitive. If senescence was caused by another protein, p16, the cells did not die and maintained high levels of p21. So the squeezing mechanism doesn't always work; it depends on the type of senescence. This discovery could help in developing drugs that selectively clear harmful senescent cells in age-related diseases, though clinical use is still a long way off.

Take the whole work

Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.

the paper's page