Interesting that Nature (highly competitive journal) is publishing negative data now. Historically it is much easier to show “no difference” in the experiment. Sloppy design or execution of the experiment almost always yields: “there is not difference” answer. The reason I think, is the popularity of Sir2, which lately enjoys lots of media and pharma attention, so Nature might want some of this attention as well.
One might argue that the current work is done with the best possible experimental design, but in reality some data seems of quite a mediocre quality.
The main conclusion from the Burnett et al. paper is that background mutations, which can be weeded out by backcrossing were the main reason, why flies and worms with enforced expression of sir2 lived longer.
Accompanying manuscript from Guarente lab shows that after backcrossing, sir2.1 overexpressing worms still live longer. Not as long as reported before, but none the less, sir2.1 extends longevity in worms.
The comment from the experts (News and Views by Lombard and Pletcher) agrees, that at least 10 generation backcross should be conducted before any meaningful data can be collected. Well… Burnett presents data with 6 generation backcross… If one looks closer at the data presented, one can see that variation in longevity between different control lines of flies is ~50%. Say, Figure 2a (+/+ control lives on average 38 days, while tub-Gal4 control lives 60 days!!!). The fact that sir2 OX flies live ~60 days as well is difficult to interpret. In reality impossible, either backgrounds are mixed up, or we ought to study longevity extending properties of GAL4 and how sir2 interacts with it.
Worm experiments are quite messy as well. During longevity experiments many worms die of unnatural causes, and scientist still debate, whether to sensor those worms or count that they died of aging. To sensor the animal out of study or not impacts data a lot, and this decision completely lies on one person, who most of the time not even blinded (so the personal interest in the data can even subconsciously be imposed onto the experiment). David Gems himself, published an observation before that shows that different strains of wild-type worms have variable longevity (~from 12 to 18 days). So seeing or not seeing some effects of longevity extending mutations can also depend on N2 strain. None of this was investigated in this study.
On the other hand ample data exist that shows that mammalian sirtuins play key roles in metabolism and diseases of aging. None of this data is disputed. And several human studies are on the way. So most likely people will keep studying sirtuins and their roles in numerous processes.
Many news companies jumped on the story (NPR, GLOBE, New York Times), but the agreement is there. Overwhelming body of evidence exist that sirtuins play a key role in many diseases of aging in mammals, it is possible that individual studies will get challenged, which is fine. It is the self-correcting nature of the scientific process. And sirtuins are not going anywhere anytime soon. They are conserved from yeast to humans!
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