After spending a decade tweaking the genomes of yeast and laboriously counting resulting cells, scientists from the Buck Institute for Research on Aging and the University of Washington have found close to 250 genes that increased the lifespan of these microbes. Importantly, a significant number of these – 189 – hadn’t been reported to be linked with aging before.
“This study looks at aging in the context of the whole genome and gives us a more complete picture of what aging is,” lead author and Buck Institute CEO and president Brian Kennedy said in a statement. “It also sets up a framework to define the entire network that influences aging in this organism.”
For the study, the team kick-started their investigation with the onerous, to put it lightly, task of probing almost 4,700 different strains of the budding yeast Saccharomyces cerevisiae. Each one had a single gene deletion, and the scientists were interested in finding out which ones imparted an effect on aging, a process typically assayed by one of two methods: chronological lifespan or replicative lifespan (RLS). The team settled on the second, which involves counting how many daughter cells are produced by a mother cell before it stops dividing.
They found that 238 of these genes were linked with longevity as determined by mother cells displaying an increased number of divisions in their absence. While the researchers generated a trove of data, published in Cell Metabolism, one gene in particular stood out. Called LOS1, the protein produced by this gene helps in the process of protein synthesis, and when deleted the RLS of the yeast was extended by an impressive 60%.
Interestingly, previous research has found that dietary restriction – demonstrated to extend the healthy lifespan of numerous simple organisms – prevents this protein from getting to its place of action in the cell. Additionally, they found that LOS1 deletion activates a gene called Gcn4 which is involved in a cellular response pathway to DNA damage.
“Calorie restriction has been known to extend lifespan for a long time,” said Kennedy in a statement. “The DNA damage response is linked to aging as well. LOS1 may be connecting these different processes.”
You may think that there is a limited amount we can learn from basic organisms like yeast, but some of these genes have also been found in the roundworm C. elegans, a model organism that has a number of genes with shared functionality to those in higher organisms, including humans. This suggests that these genes are likely not unique to yeast, but are part of conserved longevity pathways in animals.
“Almost half of the genes we found that affect aging are conserved in mammals,” said Kennedy. “In theory, any of these factors could be therapeutic targets to extend lifespan. What we have to do now is figure out which ones are amenable to targeting.”