Rejuvenation of Senescent Cells, in vitro and in vivo, by Low-frequency Ultrasound without Senolysis

Abstract

Accumulation of senescent cells in tissue and organs leads to aging abnormalities. Rejuvenating senescent cells provides a strategy to ameliorate aging. We report here that low frequency ultrasound (LFU) rejuvenates senescent cells causing growth and loss of senescence markers. With fibroblasts and mesenchymal stem cells, LFU can enable increased cell expansion without altering phenotype. At a subcellular level, LFU causes mitochondrial fission and loss of lysosome staining that is enhanced by rapamycin or Rho kinase inhibition and blocked by Sirtuin1 inhibition, consistent with the hypothesis that LFU activates autophagy. In vivo, older mice are rejuvenated by LFU as measured by increased physical performance and decreased levels of senescent cells in kidney and pancreas measured by three markers. Thus, we suggest that LFU alone increases aged cell and whole animal performance.