RT Journal Article SR Electronic T1 d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800045 DO 10.26508/lsa.201800045 VO 2 IS 1 A1 Taiki Nagano A1 Shunsuke Yamao A1 Anju Terachi A1 Hidetora Yarimizu A1 Haruki Itoh A1 Ryoko Katasho A1 Kosuke Kawai A1 Akio Nakashima A1 Tetsushi Iwasaki A1 Ushio Kikkawa A1 Shinji Kamada YR 2019 UL https://www.life-science-alliance.org/content/2/1/e201800045.abstract AB d-amino acid oxidase (DAO) is a flavin adenine dinucleotide (FAD)–dependent oxidase metabolizing neutral and polar d-amino acids. Unlike l-amino acids, the amounts of d-amino acids in mammalian tissues are extremely low, and therefore, little has been investigated regarding the physiological role of DAO. We have recently identified DAO to be up-regulated in cellular senescence, a permanent cell cycle arrest induced by various stresses, such as persistent DNA damage and oxidative stress. Because DAO produces reactive oxygen species (ROS) as byproducts of substrate oxidation and the accumulation of ROS mediates the senescence induction, we explored the relationship between DAO and senescence. We found that inhibition of DAO impaired senescence induced by DNA damage, and ectopic expression of wild-type DAO, but not enzymatically inactive mutant, enhanced it in an ROS-dependent manner. Furthermore, addition of d-amino acids and riboflavin, a metabolic precursor of FAD, to the medium potentiated the senescence-promoting effect of DAO. These results indicate that DAO promotes senescence through the enzymatic ROS generation, and its activity is regulated by the availability of its substrate and coenzyme.