The researchers used microarrays
to look at what aging does to the expression of the 20,000 or so C. elegans
genes. They found 1254 genes that changed as the animals aged. They confirmed that these genes were significant by looking at different stages of the worm and different mutants that increase or decrease the worm's lifespan.
The next step was to look at the promoters of the genes they identified as changing. Promoters are simply the part of the gene that transcription factors (TFs) stick to or bind.
The researchers found that many of these genes had a binding site for a particular class of TFs called GATA TFs. The next step was to nail down which particular GATA factor was involved in aging.
There are 14 different GATA TFs in C. elegans
. The researchers used a technique called RNA interference (RNAi
) to turn down ten of these TFs in the worm. The researchers saw no effect. But they saw an effect with three of them when they looked at what happened in mutants that lived longer.
This is the expected result if the GATA TFs extend lifespan. Basically what happened in the mutants was that when each of these three TFs was taken away, the worms no longer lived a longer life. In other words, getting rid of each of these three TFs caused the worms to have a normal lifespan.
In this study, the researchers focused on one if these three GATA factors. They focused on elt-3.
The researchers showed that the amount of elt-3 protein decreased as a worm got older. They showed that when they got rid of elt-3, genes were less affected by aging. They also showed that elt-3 is not affected by various kinds of DNA damage.
These results suggest a couple of things. First off, elt-3 is probably involved in the aging of a worm. And second, the aging is not happening because of the wear and tear of every day life. Instead, a decrease in elt-3 is just a natural part of worm aging.
It is unclear whether this research has any direct implications for human aging. A big reason why is that people are not worms.
normally lives about two weeks in the lab. This really isn't enough time to build up much DNA damage. So aging in C. elegans
is mostly programmed into its genes.
Humans on the other hand live 70 years or more. This is plenty of time to build up DNA damage. And there is a lot of data to support that DNA damage is a big part of why humans age.
But even in humans damage probably isn't the whole story. This research can teach researchers how to look for similar pathways in humans. And once scientists find them, they can then invent ways to tweak them to increase human life span.
Next researchers will need to work on preventing or fixing DNA damage. Then maybe we can routinely live past 100. Or even older.