Rejuvenation of Senescent Cells by Low Frequency Ultrasound without Senolysis

Abstract

It is believed that senescent cells are unable to grow; however, we have treated non-growing senescent cells with low frequency ultrasound (LFU) and they are rejuvenated for growth. Further, the senescent cells are characterized by low levels of motility but LFU treatment significantly increases the level of whole cell and organelle motility. At a mechanistic level, LFU causes Ca2+ entry that precedes dramatic increases in autophagy with the inhibition of mTORC1 and the movement of Sirtuin 1 from the nucleus to cytoplasm. Other characteristics of senescent cells are also reversed including blocking SASP secretion, restoring telomere length, plus nuclear 5mc levels, H3K9me3 levels, γH2AX levels, p53 nuclear staining, ROS and mitoROS levels are all restored to normal levels. Repeated LFU treatments enables expansion of primary cells and stem cells beyond normal replicative limits without altering cell phenotype. Rejuvenation is enhanced by rapamycin and Rho kinase inhibition but inhibited by blocking Sirtuin 1, Piezo1 or TRPV1. Thus, we suggest that mechanical pressure waves similar to those generated by exercise can reverse senescence at the cell level, which provides a way to rejuvenate senescent cells in vivo. One-Sentence Summary Low frequency ultrasound alone rejuvenates senescent cells by activating autophagy. Competing Interest Statement The authors have declared no competing interest.