Network of extracellular vesicles surrounding senescent cells.

Extracellular vesicles (EVs) are small lipid bilayers released from cells that contain cellular components such as proteins, nucleic acids, lipids, and metabolites. Biological information is transmitted between cells via the EV content. Cancer and senescent cells secrete more EVs than normal cells, delivering more information to the surrounding recipient cells. Cellular senescence is a state of irreversible cell cycle arrest caused by the accumulation of DNA damage. Senescent cells secrete various inflammatory proteins known as the senescence-associated secretory phenotype (SASP). Inflammatory SASP factors, including small EVs, induce chronic inflammation and lead to various age-related pathologies. Recently, senolytic drugs that selectively induce cell death in senescent cells have been developed to suppress the pathogenesis of age-related diseases. This review describes the characteristics of senescent cells, the functions of EVs released from senescent cells, and the therapeutic effects of EVs on age-related diseases. Understanding the biology of EVs secreted from senescent cells will provide valuable insights for achieving healthy longevity in an aging society.

YBX1 Regulates Satellite II RNA Loading into Small Extracellular Vesicles and Promotes the Senescent Phenotype.

Senescent cells secrete inflammatory proteins and small extracellular vesicles (sEVs), collectively termed senescence-associated secretory phenotype (SASP), and promote age-related diseases. Epigenetic alteration in senescent cells induces the expression of satellite II (SATII) RNA, non-coding RNA transcribed from pericentromeric repetitive sequences in the genome, leading to the expression of inflammatory SASP genes. SATII RNA is contained in sEVs and functions as an SASP factor in recipient cells. However, the molecular mechanism of SATII RNA loading into sEVs is unclear. In this study, we identified Y-box binding protein 1 (YBX1) as a carrier of SATII RNA via mass spectrometry analysis after RNA pull-down. sEVs containing SATII RNA induced cellular senescence and promoted the expression of inflammatory SASP genes in recipient cells. YBX1 knockdown significantly reduced SATII RNA levels in sEVs and inhibited the propagation of SASP in recipient cells. The analysis of the clinical dataset revealed that YBX1 expression is higher in cancer stroma than in normal stroma of breast and ovarian cancer tissues. Furthermore, high YBX1 expression was correlated with poor prognosis in breast and ovarian cancers. This study demonstrated that SATII RNA loading into sEVs is regulated via YBX1 and that YBX1 is a promising target in novel cancer therapy.