Abstract
Replicative aging has been demonstrated in asymmetrically dividing unicellular organisms, seemingly caused by unequal damage partitioning. Although asymmetric segregation and inheritance of potential aging factors also occur in symmetrically dividing species, it nevertheless remains controversial whether this results in aging. Based on large-scale single-cell lineage data obtained by time-lapse microscopy with a microfluidic device, in this report, we demonstrate the absence of replicative aging in old-pole cell lineages of Schizosaccharomyces pombe cultured under constant favorable conditions. By monitoring more than 1,500 cell lineages in 7 different culture conditions, we showed that both cell division and death rates are remarkably constant for at least 50–80 generations. Our measurements revealed that the death rate per cellular generation increases with the division rate, pointing to a physiological trade-off with fast growth under balanced growth conditions. We also observed the formation and inheritance of Hsp104-associated protein aggregates, which are a potential aging factor in old-pole cell lineages, and found that these aggregates exhibited a tendency to preferentially remain at the old poles for several generations. However, the aggregates were eventually segregated from old-pole cells upon cell division and probabilistically allocated to new-pole cells. We found that cell deaths were typically preceded by sudden acceleration of protein aggregation; thus, a relatively large amount of protein aggregates existed at the very ends of the dead cell lineages. Our lineage tracking analyses, however, revealed that the quantity and inheritance of protein aggregates increased neither cellular generation time nor cell death initiation rates. Furthermore, our results demonstrated that unusually large amounts of protein aggregates induced by oxidative stress exposure did not result in aging; old-pole cells resumed normal growth upon stress removal, despite the fact that most of them inherited significant quantities of aggregates. These results collectively indicate that protein aggregates are not a major determinant of triggering cell death in S. pombe and thus cannot be an appropriate molecular marker or index for replicative aging under both favorable and stressful environmental conditions.
Highlights
Replicative aging in unicellular organisms is defined by a gradual increase in generation time and probability of death as cell divisions increase
Similar age-related deterioration in physiological functions and reproduction is found in unicellular organisms that divide asymmetrically to produce morphologically distinct aged and younger cells, it has been unclear whether symmetrically dividing microbes—such as fission yeast—exhibit the same traits
Using long-term live-cell microscopy combined with a microfluidic device, we monitor the growth and death of a large number of fission yeast cells and demonstrate the existence of aging-free lineages
Summary
Replicative aging in unicellular organisms is defined by a gradual increase in generation time and probability of death as cell divisions increase. For the symmetrically dividing fission yeast S. pombe, earlier studies suggested replicative aging by observation of asymmetry in cell volume at divisions followed by the deaths of the larger cells and asymmetric segregation of carbonylated proteins (one of the biomarkers of oxidative stress). In a more recent study, Coelho et al showed that potential aging factors such as an old pole, a new spindle pole body, and protein aggregates did not correlate with generation time, suggesting that S. pombe does not age, at least under favorable conditions [11]
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