Why wait for mice? If I understand correctly, a lot of the symptoms common to aging also showup in Saccharomyces cerevisiae. The goal of the synthetic yeast project 2.0 was among other things creating chromosomes without retrotransposons, and they recently finished synthesising all 16 chromosomes, so all that is left should be assembling them? If those synthetic cells do or don’t show typical signs of aging, that should be a strong sign either way, right?
I am less excited about doing this in yeast than when I wrote this comment, but overall would still find it interesting. I find it more likely now the bottlenecks in Saccharomyces cerevisiae are sufficiently different from multicellular eukaryotes that things might not translate (even if transposons were the root cause in mice and humans). Most importantly, in yeast since they are single celled, we are mostly talking about aging of the mother cells, that split asymetrically from their daughter cells. Evolution then found weird tradeoffs that lead to bugs in mother cells with improved results in daughter cells:
For example Extrachromosomal rDNA circles (ERC) accumulates in mother cells and shortens their lifespan, but somehow this mostly doesn’t end up in the daughter cells. From my shallow investigation it seems relatively well established that deleting Fob1 significantly improves the lifetime of mother cells. The story being Fob1 is involved in the repair of rDNA, which improves growth potential of the daughter cells, but creates these ERCs that accumulate in the mother sometimes accidentally. There might be many similar examples like this, but none of these problems really translates to multicellular organisms, where this gets solved the same way as in yeast colonies through selection.
If transposons were the root cause, for aging in mother cells, then just going through gametogenesis should not reset the life-span of yeast, but it does (note though that I couldn’t quickly find a replication of this paper). When yeast perform meiosis, they split their nuclei into 4 spores and a fifth dumpster compartment leaving behind ERCs and other things that would hurt the spores.
Why wait for mice? If I understand correctly, a lot of the symptoms common to aging also show up in Saccharomyces cerevisiae. The goal of the synthetic yeast project 2.0 was among other things creating chromosomes without retrotransposons, and they recently finished synthesising all 16 chromosomes, so all that is left should be assembling them? If those synthetic cells do or don’t show typical signs of aging, that should be a strong sign either way, right?
Artificial Yeast exist now! So someone might want to run the experiment!
I am less excited about doing this in yeast than when I wrote this comment, but overall would still find it interesting. I find it more likely now the bottlenecks in Saccharomyces cerevisiae are sufficiently different from multicellular eukaryotes that things might not translate (even if transposons were the root cause in mice and humans). Most importantly, in yeast since they are single celled, we are mostly talking about aging of the mother cells, that split asymetrically from their daughter cells. Evolution then found weird tradeoffs that lead to bugs in mother cells with improved results in daughter cells:
For example Extrachromosomal rDNA circles (ERC) accumulates in mother cells and shortens their lifespan, but somehow this mostly doesn’t end up in the daughter cells. From my shallow investigation it seems relatively well established that deleting Fob1 significantly improves the lifetime of mother cells. The story being Fob1 is involved in the repair of rDNA, which improves growth potential of the daughter cells, but creates these ERCs that accumulate in the mother sometimes accidentally. There might be many similar examples like this, but none of these problems really translates to multicellular organisms, where this gets solved the same way as in yeast colonies through selection.
If transposons were the root cause, for aging in mother cells, then just going through gametogenesis should not reset the life-span of yeast, but it does (note though that I couldn’t quickly find a replication of this paper). When yeast perform meiosis, they split their nuclei into 4 spores and a fifth dumpster compartment leaving behind ERCs and other things that would hurt the spores.