Cellular senescence: unravelling complexity
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Cellular senescence might be a tumour suppressing mechanism as well as a contributor to age-related loss of tissue function. It has been characterised classically as the result of the loss of DNA sequences called telomeres at the end of chromosomes. However, recent studies have revealed that senescence is in fact an intricate process, involving the sequential activation of multiple cellular processes, which have proven necessary for the establishment and maintenance of the phenotype. Here, we review some of these processes, namely, the role of mitochondrial function and reactive oxygen species, senescence-associated secreted proteins and chromatin remodelling. Finally, we illustrate the use of systems biology to address the mechanistic, functional and biochemical complexity of senescence.
KeywordsSenescence Oxidative stress Mitochondria Secretory phenotype Systems biology Interactomes
Work leading to this paper was supported by BBSRC (CISBAN) and Research into Ageing UK.
- Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E, Gil J (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:1006–1018CrossRefPubMedGoogle Scholar
- Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495Google Scholar
- Choudhury AR, Ju Z, Djojosubroto MW, Schienke A, Lechel A, Schaetzlein S, Jiang H, Stepczynska A, Wang C, Buer J, Lee HW, von Zglinicki T, Ganser A, Schirmacher P, Nakauchi H, Rudolph KL (2007) Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet 39:99–105CrossRefPubMedGoogle Scholar
- Debacq-Chainiaux F, Borlon C, Pascal T, Royer V, Eliaers F, Ninane N, Carrard G, Friguet B, de Longueville F, Boffe S, Remacle J, Toussaint O (2005) Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-β1 signaling pathway. J Cell Sci 118:743–758CrossRefPubMedGoogle Scholar
- Jeyapalan JC, Ferreiraa M, Sedivya JM, Herbig U (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev 128:36–44Google Scholar
- Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H (2007) IntAct—open source resource for molecular interaction data. Nucleic Acids Res 35:D561–D565CrossRefPubMedGoogle Scholar
- Passos JF, von Zglinicki T (2008) Retrograde response, oxidative stress and cellular senescence. In: Miwa S, Beckman KB, Muller FL (eds) Oxidative stress in aging: from model systems to human diseases. Humana, Totowa, pp 39 52Google Scholar
- Passos JF, Saretzki G, Ahmed S, Nelson G, Richter T, Peters H, Wappler I, Birkett M, Harold G, Schaeuble K, Birch-Machin M, Kirkwood T, von Zglinicki T (2007a) Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol 5:e110CrossRefPubMedGoogle Scholar
- Wang C, Jurk D, Maddick M, Nelson G, Martin-Ruiz C, von Zglinicki T (2009) DNA damage response and cellular senescence in tissues of aging mice. Aging Cell (in press). Published online: Apr 9 2009, doi: 10.1111/j.1474-9726.2009.00481.x