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Aging and the loss of telomere sequences.
Description of the project:
- no english description available -
Eucaryotic DNA is organized linearly and is replicated when a cell proliferates. The replication mechanism is not perfect in that telomeres are shortened by each round of DNA replication. This mechanism has been suggested to play a role in cellular aging: if the length of the telomere falls below the "Hayflick constant" the cell loses its ability to replicate, a phenomenon known as "replicative senescence".
Several quantitative models have been suggested to describe replicative senescence. An important process is the evolution of the frequency of proliferating cells. The approach of Levy et al. (Telomere end-replication problem and cell aging. J. Mol. Biol., 225(4):951-960, 1992) who use a complete binary tree has been extended by Arino et al. (Mathematical modeling of the loss of telomere sequences. J. Theor. Biol., 177(1):45-57, 1995) by using branching processes.
In this project, we use the model of Aldous and Shields (A diffusion limit for a class of randomly-growing binary trees. Prob. Theo. Rel. Fields, 79(4):509-542, 1988) to study cellular ageing and senescence. Here, the proliferation rate decreases when a cell replicates, a phenomenon shown to hold true in empirical data in Portugal et al. (A computational model for telomere-dependent cell-replicative aging. BioSystems, 91(1):262-267, 2008).
Additional information: http://www.stochastik.uni-freiburg.de
Phone: 0761/203-5667
Email: peter.pfaffelhuber@stochastik.uni-freiburg.de
Runtime:
Start of project: 01.04.2008 End of project: 31.12.2009
Project Management:
Albert-Ludwigs-University Freiburg
Prof. Dr. Peter Pfaffelhuber Abteilung für Mathematische Stochastik Prof. Dr. Peter Pfaffelhuber Ernst-Zermelo-Straße 1 79104 Freiburg Germany
Phone: 0761/203-5664 Fax: 0761/203-5661 Email: sekretariat@stochastik.uni-freiburg.de
http://www.stochastik.uni-freiburg.de/pfaffelhuber
Actual Research Report
Financing:
project-related publications:
- Best K, Pfaffelhuber P: The Aldous-Shields model revisited (with application to cellular ageing). Electron Commun Prob, 2010; 15 (43): 475-488. : http://arxiv.org/abs/1004.1581
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