Autophagy mediates the mitotic senescence transition.
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.
Young
Andrew R J
AR
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
Narita
Masako
M
Ferreira
Manuela
M
Kirschner
Kristina
K
Sadaie
Mahito
M
Darot
Jeremy F J
JF
Tavaré
Simon
S
Arakawa
Satoko
S
Shimizu
Shigeomi
S
Watt
Fiona M
FM
Narita
Masashi
M
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
D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases