The researchers were able to refine their scrutiny of the gene's effect even more by exploiting the Dicer enzyme required in the RNAi process. They were able to turn off the "off" switch of RNAi using it against itself to turn genes back on. Dicer normally acts to cut up the double-stranded RNAi into small pieces that bind to the host's RNA. But Kenyon's group realized they could introduce double stranded RNA corresponding to the Dicer gene as well and inhibit RNAi itself. When they did this, the effectiveness of RNAi was reduced, and the worm's RNAi-silenced genes were turned back on. By knocking down daf-2 during early life stages, but restoring it in adults, they were able to show that the worms gained no increased lifespan protection, and that therefore the gene's life extension powers act only in the adult.
Kenyon and UCSF have applied for a patent for the use of the Dicer gene to turn off RNAi, which may be therapeutically useful. Genes could be turned off when their activity causes disease, but turned back on when the suppression is no longer needed.
The team found that daf-2-deficient worms are both longer-lived and resistant to oxidative stress damage to cells caused by charged, oxygen-bearing molecules. This supports the view that vulnerability to oxidative stress is a key -- if not the key -- cause of aging, the researchers state. Oxidative damage disrupts normal cellular function and leads to cell death. Many people take antioxidant supplements in a strategy -- still unproven -- to stave off the aging effects of oxidative damage.