title: Cellular and organismal ageing: Role of the p53 tumor suppressor protein in the induction of transient and terminal senescence.
abstract: In recent years, an impact of the p53 tumor suppressor protein in the processes of cellular and organismal ageing became evident. First hints were found in model organisms like Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster where a clear connection between ageing phenotypes and pathways that are regulated by p53, were found. Interestingly, pathways that are central to the ageing process are usually also involved in energy metabolism and are highly conserved throughout evolution. This also supports the long known empiric finding that caloric restriction has a positive impact on the life span of a wide variety of organisms. Within the last years, on the molecular level, an involvement of the insulin-like growth factor and of the histone deacetylase SRIT1 could be shown. Insight on the impact of p53 on ageing at the organismal level came from mice expressing aberrant forms of the p53 protein. Obviously, the balance of the full length p53 protein and of the shorter p44/DeltaNp53 isomer bear a strong impact on ageing. The shorter isoform regulates full length p53 and in cases where there is too much of the longer isoform, this leads to elevated apoptosis resulting in decreased tumor incidence but also in premature ageing due to exhaustion of the renewal potential. Therefore, modulating the expression of the truncated p53 isoform accordingly, might lead to increased health-span and elevated life-span.
authors.affiliation: Cell Cycle Regulation Group, Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Kramer
authors.forename: Margarita
authors.initials: M
authors.lastname: Maurer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wandl
authors.forename: Józefa
authors.initials: J
authors.lastname: Wesierska-Gadek
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C471981:COP1 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases