Researchers at the Salk Institute are resetting the clock of the aging process — in genetically engineered mice:
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. Dr. Yamanaka’s method is now routinely used to change adult tissue cells into cells very similar to the embryonic stem cells produced in the first few divisions of a fertilized egg.
Scientists next began to wonder if the four Yamanaka genes could be applied not just to cells in glassware but to a whole animal. The results were disastrous. As two groups of researchers reported in 2013 and 2014, the animals all died, some because their adult tissue cells had lost their identity and others from cancer. Embryonic cells are primed for rapid growth, which easily becomes uncontrolled.
But at the Salk Institute, Juan Carlos Izpisua Belmonte had been contemplating a different approach. He has long been interested in regeneration, the phenomenon in which certain animals, like lizards and fish, can regenerate lost tails or limbs. The cells near the lost appendage revert to a stage midway between an embryonic cell, which is open to all fates, and an adult cell, which is committed to being a particular type of cell, before rebuilding the missing limb.
This partial reprogramming suggested to him 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.
With Alejandro Ocampo and other Salk researchers, Dr. Izpisua Belmonte has spent five years devising ways to deliver a nonlethal dose of Yamanaka factors to mice. 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.
The Salk team worked first with mice that age prematurely, so as to get quick results. “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.
Isn’t this the plot to one of those incredible hulk movies? Don’t combine with gamma radiation!