In the first attempt to reverse aging by reprogramming the genome, they have rejuvenated the organs of mice and lengthened their life spans by 30 percent. The technique, which requires genetic engineering, cannot be applied directly to people, but the achievement points toward better understanding of human aging and the possibility of rejuvenating human tissues by other means.
The aging process is clocklike in the sense that a steady accumulation of changes eventually degrades the efficiency of the body’s cells. In one of the deepest mysteries of biology, the clock’s hands are always set back to zero at conception...Ten years ago, the Japanese biologist Shinya Yamanaka amazed researchers by identifying four critical genes that reset the clock of the fertilized egg. The four genes are so powerful that they will reprogram even the genome of skin or intestinal cells back to the embryonic state.The Salk Inst. researchers, using whole animals, tested the idea:
...that reprogramming is a stepwise process, and that a small dose of the Yamanaka factors might rejuvenate cells without the total reprogramming that converts cells to the embryonic state...The solution his team developed was to genetically engineer mice with extra copies of the four Yamanaka genes, and to have the genes activated only when the mice received a certain drug in their drinking water, applied just two days a week...“What we saw is that the animal has fewer signs of aging, healthier organs, and at the end of the experiment we could see they had lived 30 percent longer than control mice,” Dr. Izpisua Belmonte said.
Dr. Izpisua Belmonte believes these beneficial effects have been obtained by resetting the clock of the aging process. The clock is created by the epigenome, the system of proteins that clads the cell’s DNA and controls which genes are active and which are suppressed...He sees the epigenome as being like a manuscript that is continually edited. “At the end of life there are many marks and it is difficult for the cell to read them,” he said...What the Yamanaka genes are doing in his mice, he believes, is eliminating the extra marks, thus reverting the cell to a more youthful state.
Dr. Izpisua Belmonte said he was testing drugs to see if he could achieve the same rejuvenation as with the Yamanaka factors. The use of chemicals “will be more translatable to human therapies and clinical applications.”