I was thinking the other day that someone should do a systematic comparison of longevity genes in yeast and compare to worms/flies/mice/etc. Here's a related thing I was thinking about. Orr and Sohal published some data in flies showing that the redox potential gets less negative as the flies age. Hao Li just published a paper where he looked at the redox potential over time in individual yeast cells, and he found that it was more-or-less constant over time. This led to thinking that maybe yeast aren't a good model for aging (because cellular and organismal aging are conflated, and also because yeast aging is due at least in part to ERC accumulation). But, here's another thought:
Our cells can repair themselves, right? We have transcriptional/translational programs that allows our cells to fix themselves perfectly (i.e. a 20-year-old is just as "well-tuned" as a 10-year-old human). From an evolutionary standpoint, repair gets worse over time because natural selection stops protecting you past your peak reproductive years (more-or-less, ignoring the "grandmother hypothesis", etc.). But, physiologically, what's actually getting worse over time? It seems like the repair programs would by default remain the same (i.e. perfect). So maybe the thing to look for is parts that are "irreplacable" -- that is, things that typically have a useful lifespan longer than the reproductive years of the organism, such as stem cells and neurons.
The thing is, Orr and Sohal's data were collected from whole body homogenates (or tissue homogenates), and stem cells are a small fraction of this. But, what if the aging process has different effects in non-stem somatic cells vs. stem cells? For example, telomerase levels decline with age in stem cells. Telomerase is associated with mitochrondrial biogenesis. Differentiated cells get their mitochrondria from these depleted stem cells, so they're less able to maintain their redox potentials. So, the immediate cause would be the redox potential change, and as Orr and Sohal showed, therapeutic intervention at this level does extend lifespan. But this could be a secondary effect of the changes in stem cells.
Admittedly, this is just conjecture. I guess worms don't have stem cells, so the simplest model organism you could really test this in would be flies. But if this is right, maybe yeast are a good model organism for kind of an unexpected reason -- because stem cells matter, and yeast cells are more like stem cells than ordinary somatic cells.