Ence, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan. 3 LSI Medience Corporation, Chiyoda-ku, Tokyo 101-8517, Japan. 4 Division of Molecular Microbiology, Investigation Olmesartan impurity Angiotensin Receptor Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka 565-0871, Japan. five Division of Molecular Cell Engineering, Department of Genetics, National Institute of Genetics, ROIS, SOKENDAI, Mishima, Shizuoka 411-8540, Japan. six PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan. 7 CREST, Japan Agency for Healthcare Analysis and Development (AMED), Chiyoda-ku, Tokyo 100-0004, Japan. Correspondence and requests for supplies ought to be addressed to A.T. (e-mail: [email protected]) or to E.H. (e-mail: [email protected]).NATURE COMMUNICATIONS | 8:15287 | DOI: ten.1038/ncomms15287 | nature.com/naturecommunicationsARTICLEigher eukaryotic cells are equipped with many potent self-defence mechanisms to preserve cellular homeostasis. One such mechanism is cellular senescence, which blocks the aberrant proliferation of cells at threat for neoplastic transformation, and is therefore believed to act as an essential tumour suppressive mechanism1. Though irreversible cell-cycle arrest is traditionally thought of because the major function of senescent cells4, current studies have revealed some added functions of senescent cells1. Most noteworthy, however, could be the enhanced secretion of numerous secretory proteins, including inflammatory cytokines, chemokines, growth components and matrix metalloproteinases, in to the surrounding extracellular fluid70. These newly recognised senescent phenotypes, termed the senescence-associated secretory phenotypes9, reportedly contribute to tumour suppression7,eight, wound healing11, embryonic development12,13 and also tumorigenesis promotion9,14. As a result, senescence-associated secretory phenotypes appear to be helpful or deleterious, depending around the biological context15,16. Additionally to secretory proteins, senescent cells also boost the secretion of a class of extracellular vesicles referred to as `exosomes’17. Exosomes are endosomal membrane vesicles with diameters of B4050 nm180. They originate inside the late endosomal compartment in the inward budding of endosomal membranes, which generates intracellular multi-vesicular endosomes (MVEs)18,21. Pools of exosomes are packed in the MVEs and released in to the extracellular space following the fusion of MVEs together with the plasma membrane18,21,22. Emerging proof has indicated that exosomes play critical roles in intercellular communication, by serving as cars for transferring several cellular constituents, for example proteins, lipids and nucleic acids, involving cells237. However, incredibly tiny is recognized about the biological roles of exosome secretion in exosome-secreting cells22. Early hypotheses favoured the notion that exosomes may well function as cellular garbage bags that expel unusable cellular constituents from cells18,19. Nevertheless, this has not been explicitly proven22. Given that exosome secretion is reportedly improved in some senescent cells17, we examined the effects in the inhibition of exosome secretion in senescent cells.