Asymmetric damage segregation in spatially structured multicellular organisms

A system of spatially ordered cells with symmetric replication accumulates the most damage.

By Charlotte Strandkvist, Jeppe Juul, and Kristian Moss Bendtsen

The asymmetric distribution of damaged cellular components has been observed in species ranging from fission yeast to humans. To study the potential advantages of damage partitioning, we have developed a mathematical model describing a system of mammalian cells that duplicate damage during cell division. In particular, we consider defective mitochondria, which are thought to be a major contributor to the cellular deterioration associated with ageing. We show analytically that the asymmetric distribution of damage reduces the overall damage level of the population and delays the onset of clonal senescence. Motivated by the experimental reports of damage segregation in human embryonic stem cells, we extend the model to consider spatially structured systems of cells. Imposing spatial structure reduces, but does not eliminate, the advantage of asymmetric division over symmetric division. The results suggest that damage partitioning could be a common strategy for reducing the accumulation of damage in a range of cell types.

The article can be found here.