Reaching heathy lifespan by adapting damage retention mechanism

During cytokinesis in budding yeast (Saccharomyces cerevisiae) damaged proteins are distributed asymmetrically between the daughter and the mother cell where the retention of damaged proteins plays a crucial role in ensuring a healthy daughter cell with full replicative potential and an ageing mother cell.
In previous computational models, retention of damage is, due to simplicity, assumed to have the same efficiency throughout the cell’s replicative life, thus it is treated as a constant.  Here, based on several experimental evidences reported in yeast, we consider that damage retention, like many other processes, loses its efficiency during the replicative lifespan of the yeast cell.

We propose two strategies named as distance strategy and division strategy, to investigate the efficiency and stability of damage retention during the replicative lifespan of the single cell.  A pedigree model is used to investigate the impact of small variations in the strategies over the whole population. These impacts are based on the altruistic effects of damage retention mechanism and are measured by a cost function whose minimum value provides the optimal health and size of the population.

We speculate that that yeast cell can adjust the timing and capacity of retention mechanism, depending on the amount of damage it is exposed to.

Highlights

  • retaining more damage by a yeast cell during the early divisions increases the number of healthy daughters in the population
  • a rapid decrease in the efficiency of damage retention, at the time when the mother cell is almost exhausted, produces fewer daughters with high levels of damage
  • fluctuations in the cost function allow yeast cell to continuously vary its strategy, suggesting that optimal reproduction success is a local minimum of the cost function