Low frequency ultrasound rejuvenates senescent cells by enrichment of nuclear YAP1

Recent findings show that senescent cells are rejuvenated for growth by low frequency ultrasound (LFU) pressure waves. However, the mechanism(s) responsible for the LFU induced rejuvenation of senescent cells is not known. A number of cell components correlate with senescence but one factor that is consistently depleted with senescence and is mechanosensitive is YAP1. LFU rejuvenation of senescent cells shows an optimal power dependence such that above or below the optimal power, less rejuvenation occurs. Previous studies of mechanosensitive growth found that YAP1 nuclear localization correlated with growth. In this case, the concentration of YAP1 in the nucleus correlated with the optimal LFU power for rejuvenation for growth and autophagy. In response to LFU, YAP1 concentration in the nucleus depended upon Sirtuin1 activity and translocation of Sirtuin1 from the nucleus to the cytoplasm. Overexpression of YAP1 alone was insufficient to restore growth of senescent cells, however, the addition of cytochalasin D activated YAP1 and restored growth. When YAP1 was inactivated by verteporfin or depleted, senescent cells could no longer be rejuvenated by LFU. In a cell line with YAP-K265R mutation, induced senescent cells were not rejuvenated by LFU but expression of native YAP or YAP-K265Q enabled rejuvenation by LFU. Nuclear YAP1 was largely immobile, associated with TEAD1 on chromatin sites, and correlated with expression of cell cycle proteins. Activation of cell motility in senescent cells by cytochalasin D enhanced the concentration of YAP1 in the nucleus. We conclude that mechanical activation of YAP1 by LFU is a key mechanism underlying the rejuvenation of senescent cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.