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. 2011 Jun 24;332(6037):1554-7.
doi: 10.1126/science.1204349.

Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast

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Free PMC article

Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast

Elçin Unal et al. Science. .
Free PMC article

Abstract

Eukaryotic organisms age, yet detrimental age-associated traits are not passed on to progeny. How life span is reset from one generation to the next is not known. We show that in budding yeast resetting of life span occurs during gametogenesis. Gametes (spores) generated by aged cells show the same replicative potential as gametes generated by young cells. Age-associated damage is no longer detectable in mature gametes. Furthermore, transient induction of a transcription factor essential for later stages of gametogenesis extends the replicative life span of aged cells. Our results indicate that gamete formation brings about rejuvenation by eliminating age-induced cellular damage.

Figures

Figure 1
Figure 1. Gametogenesis resets RLS
The average number of cell divisions of the starting cell population is indicated in the graph legend. The median lifespan is written next to each curve. Error bars denote S.D. A) RLS of young and aged wild-type A702 cells directly after sorting. B) Post-sporulation RLS of spores from young and aged A702 cells. C) Age distribution of spores from A702 in individual tetrads from young and aged progenitors, n=10. The lifespan of spores from each tetrad is compared to the mean lifespan of young spores to obtain a P-value. The average P-value from 10 tetrads is 0.303 for young and 0.642 for aged spores (t-test), indicating no statistically significant difference in replicative age among spores from a given tetrad.
Figure 2
Figure 2. Sporulation eliminates age-induced cellular damage
A) Analysis of Hsp104-eGFP aggregates in aged sporulating A25825 cells. B) Quantification of Hsp104-eGFP foci in young and aged A25825 cells prior to meiosisI (mononuc), after meiosisI (binuc), after meiosisII (tetranuc) and in tetrads. C) rDNA and ERCs in young and aged A26370 cells. D) Nucleolar morphology in young and aged A26271 cells.
Figure 3
Figure 3. IME1 and NDT80 but not the meiotic nuclear divisions are required for lifespan resetting
A) RLS of young and aged A23998 (ime1Δ) cells. B) RLS of young and aged A24074 (ndt80Δ) cells. The median lifespan of the aged cells is 0. Therefore, the average is shown. C) The lifespans of young and aged A27377 (spo12Δ) cells. D) The lifespans of young and aged A24142 (cdc5-mn) spores.
Figure 4
Figure 4. Transient NDT80 expression extends the lifespan of vegetatively growing aged cells
A) Lifespan of young and aged cells from A25823 (GAL4.ER, NDT80) and A25824 (GAL4.ER, GAL-NDT80). B) Top; description of the experiment, bottom; aged cells from A27507 (GAL4.ER, NDT80) and A27484 (GAL4.ER, GAL-NDT80) labeled before and after β-estradiol. C) The number of cell divisions after β-estradiol treatment was calculated by the difference between the green- and red-labeled bud scars. The distribution of n=60 cells is shown for A27507 (GAL4.ER, NDT80) and n=100 cells for A27484 (GAL4.ER, GAL-NDT80). D) Fob1-GFP in young and aged cells from strains A27507 (GAL4.ER, NDT80) and A27484 (GAL4.ER, GAL-NDT80) after 6th β-estradiol treatment. E) Percentage of cells with enlarged Fob1-GFP from A27507 (GAL4.ER, NDT80) and A27484 (GAL4.ER, GAL-NDT80) following β-estradiol treatment. The average of two independent experiments is shown. 100 – 200 cells were counted for each time point; error bars display the range.

Comment in

  • Ageing: recapturing youth.
    Wrighton KH. Wrighton KH. Nat Rev Mol Cell Biol. 2011 Jul 22;12(8):466. doi: 10.1038/nrm3160. Nat Rev Mol Cell Biol. 2011. PMID: 21779021 No abstract available.

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