doi: 10.1016/j.cub.2013.07.084. Epub 2013 Sep 12.
Fission yeast does not age under favorable conditions, but does so after stress
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- PMID:24035542
- PMCID: PMC4620659
- DOI: 10.1016/j.cub.2013.07.084
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Fission yeast does not age under favorable conditions, but does so after stress
Miguel Coelho et al. Curr Biol..
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Abstract
Background: Many unicellular organisms age: as time passes, they divide more slowly and ultimately die. In budding yeast, asymmetric segregation of cellular damage results in aging mother cells and rejuvenated daughters. We hypothesize that the organisms in which this asymmetry is lacking, or can be modulated, may not undergo aging.
Results: We performed a complete pedigree analysis of microcolonies of the fission yeast Schizosaccharomyces pombe growing from a single cell. When cells were grown under favorable conditions, none of the lineages exhibited aging, which is defined as a consecutive increase in division time and increased death probability. Under favorable conditions, few cells died, and their death was random and sudden rather than following a gradual increase in division time. Cell death correlated with the inheritance of Hsp104-associated protein aggregates. After stress, the cells that inherited large aggregates aged, showing a consecutive increase in division time and an increased death probability. Their sisters, who inherited little or no aggregates, did not age.
Conclusions: We conclude that S. pombe does not age under favorable growth conditions, but does so under stress. This transition appears to be passive rather than active and results from the formation of a single large aggregate, which segregates asymmetrically at the subsequent cell division. We argue that this damage-induced asymmetric segregation has evolved to sacrifice some cells so that others may survive unscathed after severe environmental stresses.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Figures
(A) Left: the pole identity in the founder cell is not known (white arcs at 0′). After the first division (generation 1), the old (magenta arc) and new (green arc) pole segregate asymmetrically (generation 2). Right: pedigree tree of 52 microcolonies (NCYC132) representing average division times (length of vertical lines) of new pole (left branch, green) and old pole (right branch, magenta) cells. The bifurcations represent cell divisions. Horizontal lines (gray) mark the first division in each generation (gen). The scale bar represents 5 μm. (B) Cells that consecutively inherit the old pole (magenta) or the new pole (green) do not exhibit an increase in division time (strain NCYC132; n = 52 cell lineages; Movie S1). For comparison, we show the division times forE. coli (estimated for old-pole cells from Figure 3A in [7]) andS. cerevisiae (estimated from a linear fit for mother cells of age two to ten generations from Figure 2 in [19], normalized by the division time of the cells of the second generation). (C–E) Cells that consecutively inherit the old spindle pole body (magenta) or the new spindle pole body (green, labeled with Cdc7-GFP, strain IH1106; n = 13 cell lineages; Movie S2) (C) or inherit a higher amount of protein aggregates (magenta) or a lower amount of protein aggregates (green, strain MC19; n = 30 cell lineages; Movie S2) (D) or are born smaller (orange) and larger (blue) in asymmetrically dividing cells (pom1Δ strain JB107; n = 32 cell lineages; Movie S2) (E) do not show an increase in division time with an increasing division number. Data are mean ± SEM; the number of cells is given in the graphs. (F) Average division time of cells that consecutively inherit the old pole (thick magenta line, n = 10 spores) or the new pole (thick green line, n = 32 spores, T = 23°C ± 2°C; thin lines represent the SEM) from micromanipulation experiments (inset). Death events related to the old/new pole inheritance were not observed. For comparison, we show division times forS. cerevisiae (estimated for mothers cells from Figure 1 in [19], multiplied by 3.6 to match the scale). See also Figure S1 and Movies S1 and S2.
(A) Aging scenarios: (1) one daughter cell (D1) inherits more damage and divides slower than its mother (M), (2) both daughter cells (D1, D2) divide slower than their mother (M), and (3) both daughter cells (D1, D2) divide equally fast or faster than their mother (M), hence there is no aging. Green trash bins represent aging factors. (B) Identification of anS. pombe lineage of putatively aging cells: the slower-dividing mothers (green) and the slower-dividing daughters (magenta) that divide later than their siblings. The scale bar represents 5 μm. The time is given in minutes. (C)S. pombe mother cells with a long division time (1 SD above the average, n = 107) generated daughters with a shorter division time. A histogram of division times normalized by the mother’s division time is shown. The mean value of the daughter division time was significantly smaller than 1 (p = 10−21). In cells that exhibit aging, the average normalized daughter division time was greater than 1 (S. cerevisiae, [19]; human fibroblasts, [33]). (D) The division time of the cells with a higher division time than their sibling (slower-dividing sibling) decreased by 0.0099 per division (r = −0.96, 95% confidence interval for r = [−1.00, −0.71], p = 0.002, the number of cells is shown). See also Figure S2.
(A) A cell (yellow) divided (100 min) and one of the daughter cells died (magenta at 105 min). Cell death was recognized by a distinct cell morphology [38] (shrinkage of cell volume and surface irregularities), as well as by the absence of growth. The morphology, growth, and division of the cell before death (yellow), as well as of the surviving sister cell (green), were normal (Movie S1). (B) Normalized division time as a function of the number of divisions before death decreased on average by 0.7% ± 0.6% per division; p = 0.2, n = 36 cells (34 dead cells with surviving sisters and two dead sister cells; 174 cell divisions in total). For comparison, division time forS. cerevisiae is shown (taken from Figure 2 and the text in [19]). (C) Time lapse of the last division before cell death after inheritance of a putative aging factor (OP, old cell pole; NP, new cell pole; OS, old SPB; NS, new SPB; MAgg, more aggregates; LAgg, less aggregates; L, larger cell; S, smaller cell). The percentage of cell deaths associated with the inheritance of a factor is shown on the right; strains are shown on the left; BF, bright field. White lines encircle cells. (D) The probability of death in the next cell cycle after inheritance of a putative aging factor is shown (n > 5,000 cell divisions, the number of cells is given in the graph). Data are means ± SEM; scale bars represent 5 μm. See also Figure S3.
(A) Bright-field (BF) and fluorescence images of a strain expressing Hsp104-GFP, and the corresponding schemes. The cell with a large amount of protein aggregates died (magenta edge), while its sister survived (white edge). The scale bar represents 1 μm. The time is given in minutes. (B) Aggregate amount (A, Hsp104-GFP intensity in arbitrary units, a.u.) and puncta number (N) for dead cells (magenta), their sisters (green), and the population (black). (C) Death frequency in cells born with Hsp104-GFP intensity or aggregate number above (magenta) and below (green) the death threshold,d (d=5 a.u. for A, defined as three times the average of the population; or 2 aggregates for N, see B). The data are means ± SEM. The number of cells from more than three independent experiments is given in the graphs. See also Figures S3 and S4 and Movie S3.
(A) Images of cells that inherit large aggregates (Hsp104-GFP, green) after heat (40°C, 1 hr; left) and oxidative (1 mM H2O2; right) stress. Schemes depict aggregate formation and cell death (magenta), which occurred two to five cell divisions after stress. Scale bars represent 5 μm. Time is given in minutes. (B) Normalized division time before death increased for cells inheriting large aggregates (solid lines, Hsp104-GFP intensity I > 5 a.u.), but not for cells clean of aggregates (dashed lines, Hsp104-GFP intensity I< 5 a.u.). (C) Cells inheriting a larger amount of aggregates had a higher probability of death than cells inheriting a smaller amount, indicating that after stress protein aggregates behave as an aging factor. Data are means ± SEM. The number of cells is shown in the graphs. (D) Scheme representing the transition between nonaging and aging inS. pombe. Under favorable growth conditions, aging factors (protein aggregates, depicted as trash bins) distribute equally between both siblings and aging is not present. After stress, a high amount of aging factors is asymmetrically segregated to one cell, giving rise to a clean sibling. The cell that inherits a large amount of aging factors undergoes aging and death. See also Figure S5 and Movie S4.
Comment in
- Cellular aging: symmetry evades senescence.Moseley JB.Moseley JB.Curr Biol. 2013 Oct 7;23(19):R871-3. doi: 10.1016/j.cub.2013.08.013.Curr Biol. 2013.PMID:24112980Free PMC article.
References
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