We've come leaps and bounds, but many of the intricate details of cellular aging remain a mystery to us. Yeast are a great organism to study because they replicate quickly and you can quickly evaluate many generations. Results on yeast don't necessarily translate to large, multi-cellular organisms like humans, but they're usually a good starting point. Understanding what makes yeast age reveals key areas and genes to look for in ourselves; after all many essential genes are conserved down the line. These may have been changed through evolution, but many remain strikingly similar.
What genes regulate a cell's lifespan?
A 10 year study using yeast at the Buck Institute has discovered 238 genes that hinder longevity. The exhaustive study looked at 4,698 yeast strains in which one gene had been deleted, and counted how many times these cells could divide through careful microscopic analysis.
We already know a few genes that have an effect on lifespans, at least in model organisms. Examples include mTOR, AMPK, insulin/IGF-1 signalling pathways and the Sirtuin gene family. These revolve around cellular energy, construction, and gene repair. This study revealed 189 extra 'aging' genes that we didn't know about before.
One of the strongest results in the study was deletion of LOS1, which helps build proteins. LOS1 is again connected to mTOR, a control switch that regulates cell growth. LOS1 also had effects on a gene Gcn4 which deals with DNA damage.
“Calorie restriction has been known to extend lifespan for a long time. The DNA damage response is linked to aging as well. LOS1 may be connecting these different processes.”
Before we get carried away
Although the study was expansive, it looked at single deletions which doesn't reveal enough information about how different networks connect and influence each other. Working out exactly what each gene does is also important, and whether it can be applied to humans or not. Trying to understand genes is often a slow process, and we're learning more all the time. Aging obviously effects different species in dramatically different ways and speeds, but it's likely results on yeast are a gateway to further research. How many times a cell can divide also doesn't necessarily indicate overall lifespan, as multi-cellular organisms operate on a very different level to single celled ones.
“Almost half of the genes we found that affect aging are conserved in mammals. In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure out which ones are amenable to targeting.”
Read more at The Buck Institute