Tissue turnover and rejuvenation through mechanics.

Tissue turnover depends on the efficient removal of damaged cells to maintain structural and functional integrity. Cells respond to damage across a spectrum of outcomes, ranging from repair and recovery to senescence, apoptosis, and malignant transformation. This review focuses on apoptosis and senescence in epithelia as two outcomes with profound consequences for tissue homeostasis, one ensuring swift mechanical removal of damaged cells and the other driving persistent tissue disruption. While apoptotic cells are efficiently eliminated through coordinated mechanical processes, senescent cells resist elimination and progressively impair tissue function through chronic inflammation and mechanical remodeling of the tissue microenvironment. Restoring tissue function therefore requires strategies to efficiently clear or reverse the senescent state. Immune-mediated clearance and senolytic drugs can reduce senescent cell burden, yet their efficacy and selectivity remain limited. Emerging mechanobiological strategies, including low-frequency ultrasound and geometric confinement, offer a complementary approach by directly reversing the senescent phenotype through physical cues. Ultimately, harnessing these mechanical forces offers a promising avenue toward restoring tissue function.