Mechanotransduction is the Janus-faced regulator of cell aging

Abstract Aging is inevitable during development, and we still lack methods to rejuvenate it due to the poor understanding. A wealth of studies focused on the biochemical signaling pathways for inducing cell senescence, whereas the role of mechanotransduction during the process had been ignored. Here, we clarified how cell mechanosensing was involved and played functional roles in cellular senescence. The intracellular traction force and mechanotransduction could reduce in response to mesenchymal stem/stromal cell aging. Compensating the cell traction force via physical or chemical stimulation seems an attractive strategy for temporarily reversing aging markers, however, mechanical overstimulation triggers accelerated cellular senescence shortly afterwards. We further clarified that DNA damage results in the reduction of cellular mechanotransduction, which is a self-protective mechanism as it endows cells with resistance to further DNA damage, although it inhibits cell proliferation and many other functions. Taken together, we have disclosed the interplay between DNA damage, cellular mechanics, and senescence, confirming the two-side effects of the mechanical cues in the aging process.