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bioRxiv · 10.1101/628669

Stochastic modeling of aging cells reveals how damage accumulation, repair, and cell-division asymmetry affect clonal senescence and population fitness

Song, R.·Acar, M.
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Abstract

BackgroundAsymmetry during cellular division, both in the uneven partitioning of damaged cellular components and of cell volume, is a cell biological phenomenon experienced by many unicellular organisms. Previous work based on a deterministic model claimed that such asymmetry in the partitioning of cell volume and of aging-associated damage confers a fitness benefit in avoiding clonal senescence, primarily by diversifying the cellular population. However, clonal populations of unicellular organisms are already naturally diversified due to the inherent stochasticity of biological processes.\n\nResultsApplying a model of aging cells that accounts for natural cell-to-cell variations across a broad range of parameter values, here we show that the parameters directly controlling the accumulation and repair of damage are the most important factors affecting fitness and clonal senescence, while the effects of both segregation of damaged components and division asymmetry are frequently minimal and generally context-dependent.\n\nConclusionsWe conclude that damage segregation and division asymmetry, perhaps counterintuitively, are not necessarily beneficial from an evolutionary perspective.

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Song, R., Acar, M.. 2019-05-05. Stochastic modeling of aging cells reveals how damage accumulation, repair, and cell-division asymmetry affect clonal senescence and population fitness. https://doi.org/10.1101/628669

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