Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells.
Level 5 - mechanism / opinion, no new human data
Bench research in a model organism (yeast); Level 5 under Oxford CEBM.
PubMed 28302853 · doi:10.1126/science.aaj2103
What was done
Researchers tested whether the NAD+-dependent deacetylase Sir2 becomes nonfunctional during yeast aging and whether heterochromatin silencing at the HML and HMR loci declines in aging mother cells. They evaluated the mating response initiation and pheromone sensitivity in young versus old yeast cells, and tested the effect of deleting the polyglutamine domain of the RNA-binding cell-cycle regulator Whi3 on pheromone sensitivity in aged cells.
What was found
Heterochromatin silencing at the HML and HMR loci was not lost during aging. Old cells were able to initiate a mating response but were less sensitive to mating pheromone than young cells due to age-dependent aggregation of Whi3. Removal of the Whi3 polyglutamine domain restored pheromone sensitivity in old cells. No numerical values or statistical effect sizes were reported in the abstract.
Why it matters
This study refutes a long-standing model that Sir2-dependent loss of heterochromatin silencing drives replicative sterility in aging yeast, attributing the phenotype instead to protein aggregation of a specific cell-cycle regulator.
Limits
The abstract reports no sample sizes, effect magnitudes, or quantitative metrics. The study is conducted entirely in a unicellular model organism (yeast) mating system, and the findings cannot be directly extrapolated to multicellular organismal or human aging.
Cited by
- context As yeast cells age, they lose their A or alpha mating-type identity and become sterile.