title: Senescence and apoptosis: dueling or complementary cell fates?
abstract: In response to a variety of stresses, mammalian cells undergo a persistent proliferative arrest known as cellular senescence. Many senescence-inducing stressors are potentially oncogenic, strengthening the notion that senescence evolved alongside apoptosis to suppress tumorigenesis. In contrast to apoptosis, senescent cells are stably viable and have the potential to influence neighboring cells through secreted soluble factors, which are collectively known as the senescence-associated secretory phenotype (SASP). However, the SASP has been associated with structural and functional tissue and organ deterioration and may even have tumor-promoting effects, raising the interesting evolutionary question of why apoptosis failed to outcompete senescence as a superior cell fate option. Here, we discuss the advantages that the senescence program may have over apoptosis as a tumor protective mechanism, as well as non-neoplastic functions that may have contributed to its evolution. We also review emerging evidence for the idea that senescent cells are present transiently early in life and are largely beneficial for development, regeneration and homeostasis, and only in advanced age do senescent cells accumulate to an organism's detriment.
authors.affiliation: Departments of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Bennett G
authors.initials: BG
authors.lastname: Childs
authors.affiliation: Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA baker.darren@mayo.edu vandeursen.jan@mayo.edu.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Baker
authors.affiliation: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
authors.affiliation: Departments of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA baker.darren@mayo.edu vandeursen.jan@mayo.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D016922:Cellular Senescence; D006801:Humans; D015398:Signal Transduction; D013312:Stress, Physiological
keywords: aging; apoptosis; cancer; embryogenesis; senescence