Multimodal label-free imaging reveals increased nuclear hydration and apparent stiffening during cellular senescence

Cellular senescence is accompanied by complex changes in nuclear mechanics. Here, integrated Raman, Brillouin, and refractive index imaging quantitatively revealed that senescent nuclei exhibit an increased high-frequency viscoelastic response, despite the increase in nuclear water content and volume and the decrease in biomolecular density. This discrepancy indicates that the nuclear mechanical alteration in senescent cells is not simply due to molecular condensation, as discussed in the context of chromatin reorganization.