title: Autophagy mediates the mitotic senescence transition.
abstract: As a stress response, senescence is a dynamic process involving multiple effector mechanisms whose combination determines the phenotypic quality. Here we identify autophagy as a new effector mechanism of senescence. Autophagy is activated during senescence and its activation is correlated with negative feedback in the PI3K-mammalian target of rapamycin (mTOR) pathway. A subset of autophagy-related genes are up-regulated during senescence: Overexpression of one of those genes, ULK3, induces autophagy and senescence. Furthermore, inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. Our data suggest that autophagy, and its consequent protein turnover, mediate the acquisition of the senescence phenotype.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: Andrew R J
authors.initials: AR
authors.lastname: Young
authors.forename: Masako
authors.initials: M
authors.lastname: Narita
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferreira
authors.forename: Kristina
authors.initials: K
authors.lastname: Kirschner
authors.forename: Mahito
authors.initials: M
authors.lastname: Sadaie
authors.forename: Jeremy F J
authors.initials: JF
authors.lastname: Darot
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
authors.forename: Masashi
authors.initials: M
authors.lastname: Narita
mesh_terms: D000375:Aging / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases