The technique is frequently used by laboratories to manufacture stem cells.
Life expectancy has increased more than twofold in the developed world over the past two centuries. Thanks to childhood vaccines, seat belts, and so on, more people than ever reach natural old age. But each generation brings new possibilities, as the epigenome gets reset during reproduction when a new embryo is formed.
Cloning takes advantage of reprogramming, too: a calf cloned from an adult bull contains the same DNA as the parent, just refreshed. If so, then reversing these epigenetic changes through reprogramming may enable us to turn back aging itself. As he sees it, there is no reason to think we cannot extend human life span by another 30 to 50 years, at least. Starting in , Yamanaka demonstrated how adding just four proteins to human adult cells could reprogram them so that they look and act like those in a newly formed embryo.
These proteins, called the Yamanaka factors, function by wiping clean the epigenetic marks in a cell, giving it a fresh start. The artificially reprogrammed cells are called induced pluripotent stem cells, or IPSCs. Like the stem cells in embryos, they can then turn into any kind of body cell—skin, bone, muscle, and so on—if given the right chemical signals. In Japan, researchers began an effort to reprogram cells from a Japanese woman in her 80s with a blinding disease, macular degeneration.
In , the woman became the first person to receive a transplant of such lab-made tissue.
Before then, though, researchers at the Spanish National Cancer Research Centre had already taken the technology in a new direction when they studied mice whose genomes harbored extra copies of the Yamanaka factors. Turning these on, they demonstrated that cell reprogramming could actually occur inside an adult animal body, not only in a laboratory dish. The experiment suggested an entirely new form of medicine. But it also underscored the dangers. It can also become a cancer cell. It proved that cellular reprogramming had indeed occurred inside their bodies, but the results were usually fatal.
He was inspired by salamanders, which can regrow an arm or tail. Researchers have yet to determine exactly how amphibians do this, but one theory is that it happens through a process of epigenetic resetting similar to what the Yamanaka factors achieve, though more limited in scope. Could the same thing be done to an entire animal? Could it be rejuvenated just enough? In , the team devised a way to partially rewind the cells in mice with progeria.
They genetically modified the mice to produce the Yamanaka factors in their bodies, just as the Spanish researchers had done; but this time, the mice would produce those factors only when given an antibiotic, doxycycline. In another experiment, others got it just for two days out of every seven. You can easily turn it on or off.
But the mice that drank a limited dose did not develop tumors. Instead, they became more physically robust, their kidneys and spleens worked better, and their hearts pumped harder. To West, the technology offers the prospect that humans, like salamanders, could regenerate tissues or damaged organs. To others, however, the evidence for rejuvenation is plainly in its infancy.
Progeria is an illness due to a single DNA mutation. Would the rejuvenation technique work in naturally aged animals and in human cells? When the longevity gene was injected in aging mice, they were made to seem young again, with a remarkable reversing of physical decline and degeneration.
In some cases, the protein was found even found to regenerate deteriorated cells — a huge breakthrough in repairing damage caused by aging. Of course, we are a long way from using the longevity gene in our own bodies, but the study is a promising sign that aging can be reversed — a dream not only for scientists but the entire aging population as well.
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