title: Autophagy and senescence: a partnership in search of definition.
abstract: Autophagy and senescence share a number of characteristics, which suggests that both responses could serve to collaterally protect the cell from the toxicity of external stress such as radiation and chemotherapy and internal forms of stress such as telomere shortening and oncogene activation. Studies of oncogene activation in normal fibroblasts as well as exposure of tumor cells to chemotherapy have indicated that autophagy and senescence are closely related but not necessarily interdependent responses; specifically, interference with autophagy delays but does not abrogate senescence. The literature relating to this topic is inconclusive, with some reports appearing to be consistent with a direct relationship between autophagy and senescence and others indicative of an inverse relationship. Before this question can be resolved, additional studies will be necessary where autophagy is clearly inhibited by genetic silencing and where the temporal responses of both autophagy and senescence are monitored, preferably in cells that are intrinsically incapable of apoptosis or where apoptosis is suppressed. Understanding the nature of this relationship may provide needed insights relating to cytoprotective as well as potential cytotoxic functions of both autophagy and senescence.
authors: Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. gewirtz@vcu.edu
authors: David A
authors: DA
authors: Gewirtz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species
keywords: autophagy; senescence