Comparison of the mtDNA Molecule Level Model and the Cell Level Model

When you are preparing to build a simulation model of mtDNA in aging, how do you choose the level of detail for the model? The ability to follow individual mtDNA molecules in the mtDNA Molecule Level model makes this approach flexible. It is easier to add new mechanisms to this model, and it is easier to make the characteristics of the mtDNA molecules variable, such as including a replicative advantage to a deletion mutation but not for a point mutation, for example. The price is that the mtDNA Molecule Level simulations require more computation resources than the Cell Level simulations. The mtDNA Molecule Level models are practically limited to simulating a few thousand cells over 100 years.

The Cell Level simulations can model up to a million cells over a time span of a century. This ability to model large numbers of cells is their main advantage. The disadvantage is that adding lower level detail, such as distinguishing between different mtDNA mutants, significantly increases the computational time required and is also difficult to implement. In my experience this type of model is less flexible than the mtDNA Molecule Level models. Also, the presentation of this type of model generally involves more mathematics, and that can be a barrier to communication with the intended biomedical audience.

The choice between the two levels of model often boils down to a practical consideration. Do you have enough computational power available to use the simple and flexible mtDNA Molecular Level model, or do you need the efficiency of the Cell Level simulations? As a guide in making this choice, we present some measurements of the computational time requirements of both models, as a function of the number of simulated cells and the average number of mtDNA molecules per cell. The simulation times were measured on a 2 GHz Pentium 4 CPU with 512 MB RAM running LINUX. Each simulation was run for 100 years, with approximately 1,000 mtDNA molecules in each cell (average value). For both simulation methods the computational time rises linearly with the number of simulated cells (see Figure 48.2).

However, the mtDNA Molecule Level simulation requires 54 seconds per cell per century, whereas the Cell Level model requires only 1.3 seconds per cell per century, a factor of 40 difference.

5,000 10,000 15,000 20,000

Number of Simulated Cells

Figure 48.2 Computational time required as a function of the number of compartments simulated for the two simulation methods. Each simulated cell containing approximately 1,000 mtDNA molecules. Simulations were run for 100 years, with a time step of one hour.

5,000 10,000 15,000 20,000

Number of Simulated Cells

Figure 48.2 Computational time required as a function of the number of compartments simulated for the two simulation methods. Each simulated cell containing approximately 1,000 mtDNA molecules. Simulations were run for 100 years, with a time step of one hour.

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