Autophagy, a cellular process that degrades and recycles proteins and organelles, plays a key role in the transition from mitotic proliferation to senescence. This study shows that autophagy is activated during senescence and is involved in the acquisition of the senescent phenotype. Autophagy is regulated by the PI3K-mTOR pathway, and its activation is associated with negative feedback in this pathway. A subset of autophagy-related genes is up-regulated during senescence, and overexpression of one of these genes, ULK3, induces autophagy and senescence. Inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. The study also shows that autophagy contributes to the efficient transition from a proliferative to a senescent state by facilitating rapid protein turnover. Autophagy is activated during oncogene-induced senescence (OIS), a tumor-suppressive process that prevents cancer development. The study demonstrates that autophagy is involved in the regulation of OIS through the mTORC1 and mTORC2 pathways. Autophagy is also involved in the regulation of senescence-associated secreted factors, which are important for the functional activity of senescent cells. The study shows that autophagy contributes to the establishment of senescence arrest and that its inhibition delays the senescence phenotype. The findings suggest that autophagy is a key effector mechanism of senescence and that it plays a critical role in the transition from mitotic proliferation to senescence.Autophagy, a cellular process that degrades and recycles proteins and organelles, plays a key role in the transition from mitotic proliferation to senescence. This study shows that autophagy is activated during senescence and is involved in the acquisition of the senescent phenotype. Autophagy is regulated by the PI3K-mTOR pathway, and its activation is associated with negative feedback in this pathway. A subset of autophagy-related genes is up-regulated during senescence, and overexpression of one of these genes, ULK3, induces autophagy and senescence. Inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. The study also shows that autophagy contributes to the efficient transition from a proliferative to a senescent state by facilitating rapid protein turnover. Autophagy is activated during oncogene-induced senescence (OIS), a tumor-suppressive process that prevents cancer development. The study demonstrates that autophagy is involved in the regulation of OIS through the mTORC1 and mTORC2 pathways. Autophagy is also involved in the regulation of senescence-associated secreted factors, which are important for the functional activity of senescent cells. The study shows that autophagy contributes to the establishment of senescence arrest and that its inhibition delays the senescence phenotype. The findings suggest that autophagy is a key effector mechanism of senescence and that it plays a critical role in the transition from mitotic proliferation to senescence.