title: Stressing the cell cycle in senescence and aging.
abstract: Senescence represents a permanent exit from the cell cycle and its role in curtailing the proliferation of damaged and potentially oncogenic cells has relevance both as a front-line defense against cancer and as an underlying cause of aging. The retinoblastoma protein (RB) and p53 tumor suppressors are central to the process and the growth arrest is primarily implemented by the cyclin-dependent kinase (CDK) inhibitors, p16INK4a and p21CIP1. In contrast to terminal differentiation, senescence is a general response to a diverse range of cellular stresses and is typically accompanied by a characteristic set of phenotypic changes. Of particular note is a secretory program whose autocrine and paracrine effects can advertize the presence of senescent cells within a tissue and promote their clearance by the immune system. In this short review, we will highlight recent advances in understanding the relationship between senescence and aging and the distinction between senescence and terminal differentiation, from a cell cycle perspective.
authors.affiliation: CRUK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Hollie
authors.initials: H
authors.lastname: Chandler
authors.forename: Gordon
authors.initials: G
authors.lastname: Peters
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D050684:E2F Transcription Factors / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53