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#102: Cellular Reprogramming

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This is an excerpt from the book Lifespan: Why We Age – and Why We Don’t Have To about cellular reprogramming.

In 2006, the Japanese stem cell researcher Shinya Yamanaka announced to the world that after testing dozens of combinations of genes, he had discovered that a set of four ——Oct4, Klf4, Sox2, and c-Myc—— could induce adult cells to become pluripotent stem cells, or iPSCs, which are immature cells that can be coaxed into becoming any other cell type. These four genes code for powerful transcription factors that each controls entire sets of other genes that moce cells around on the Waddington landscape during embryonic development. these genes are found in most multicellular species, including chimpanzees, monkeys, dogs, cows, mice, rats, chickens, fish, and frogs. For his discovery in petri dish, Yamanaka won the Nobel Prize in Physiology or Medicine along with John Gurdon in 2012. We now call these four genes Yamanaka factors… - Lifespan: Why We Age – and Why We Don’t Have To

…I predict that cellular reprogramming in the body will first be used to treat age-related diseases in the eye, such as glaucoma and macular degeneration (the eye is the organ of choice to trial gene therapies because it is immunologically isolated). But if the therapy is sage enough to deliver into the entire body——as the long-term mouse studies in my lab suggest they might one day be—— this may be in our future: At age 30, you would get a week’s course of three injections that introduce a specially engineered adeno-associated virus, or AAV, which causes a very mild immune response, less even than what is commonly caused by a flu shot. The virus, which has been known to scientists since the 1960s, has been modified so it doesn’t spread or cause illness. What this theoretical version of the virus would carry would be a small number of genes——some combination of Yamanaka factors, perhaps——and a fail-safe switch that could be turned on with a well-tolerated molecule such as doxycycline, an antibiotic that can be taken as a tablet, or, even better, once that’s completly inert. Nothing, at that point, would change the way your genes work. But when you began to see and feel the effects of aging, likely sometime in you mid-40s, you would be prescribed a month’s course of doxycycline. With that, the reprogramming genes would be switched on. During the process, you’d likely place a drop of blood in a home biotracker or pay a visit to the doctor to make sure the system was working as expected, but that’s about it. Over the next month, your body would undergo a rejuvenation process as Waddington’s marbles were sent back to where they once were when you were young. Gray hair would disappear. Wound would heal faster, hear higher-pitched sounds, and no longer need glasses to read a menu. Your body would feel young again. Like Benjamin Button, you would feel 35 again. Then 30. Then 25. But unlike Benjamin Button, that’s where you would stop. The prescription would be discontinued. The AAV would switch off. The Yamanaka factors would fall silent. Biologically, physically, and mentally, you would be a couple of decades younger, but you’d retain all your knowledge, wisdom, and memories. You would be young again, not just looking young but actually young, free to spend the next few decades of your life without the aches and pains of middle age, untroubled by the prospects of cancer and heart disease. Then, a few more decades down the road, when those gray hairs begin showing up again, you’d start another cycle of the prescribed trigger. What’s more, with the pace at which biotech is adcancing, and as we learn how to manipulate the factors that reset our cells, we may be able to move away from using viruses and simply take a month’s course of pills. Does that sound like science fiction? Somethng that is very far out in the future? Let me be clear: it’s not.- Lifespan: Why We Age – and Why We Don’t Have To