Senescent cells spread senescence to neighbours via tiny vesicles in cell study
Senescent cells are known to push neighbouring cells toward senescence too. But how they do that without classical inflammatory signals was unclear. New research points to tiny membrane-enclosed particles that cells release into their surroundings.
Researchers worked with human fibroblasts, connective tissue cells. They triggered cellular aging by making cells produce too much p16INK4a, a protein that stops cells from dividing. These cells did not release the typical inflammatory signals (such as IL-6 and IL-8) that aging cells are known to send out. Yet they could still pass on aging to neighbouring cells.
Small extracellular vesicles carry the signal
The researchers showed that fibroblasts producing p16INK4a released far more tiny membrane-wrapped particles called small extracellular vesicles than dividing cells do. These particles are released by cells to send signals to their surroundings. The particles from aging cells were biologically active: they stopped cell division in the cells that received them, raised p16INK4a levels, and triggered a DNA damage response, all without setting off the usual chain of inflammation.
Effect seen with cells from aged donors
The same pattern emerged in two additional models of cellular ageing: cells expressing progerin (a protein that mimics aspects of ageing) and cells with dysfunctional telomeres (the protective caps at chromosome ends). Crucially, vesicles isolated from fibroblasts derived from aged human donors induced senescence in fibroblasts from young donors. This suggests that extracellular vesicles represent a mechanism by which senescence can spread between cells during normal biological ageing.
Search terms to explore further: paracrine senescence extracellular vesicles | p16INK4a cell cycle arrest fibroblasts | senescence propagation without inflammation