 Earlier episodes in this series covered how aging involves changes in the epigenome, the molecular features attached to DNA that affect which genes get expressed. This time we're going to focus on what happens to the epigenome when scientists turn back the clock and make cells younger. Welcome to X10, your one stop YouTube show for all things life extension. Learn the science, keep up with new research and live longer and healthier. To get updates from X10, click the red button below to subscribe and don't forget to hit the bell icon and select all notifications. In 2006 researchers in Japan figured out how to turn cells from your body, say muscle cells, back into undifferentiated cells known as stem cells. They accomplished this by expressing four genes known as Yamanaka factors or OSKM factors, an acronym based on the names of the four genes. The resulting cells are called induced pluripotent stem cells or IPSCs. It's a fancy phrase basically meaning that IPSCs have been forced to become cells that can divide forever and produce daughters that can become any type of cell. It turns out that this reprogramming doesn't just turn differentiated cells into IPSCs. It also reverses a lot of the changes normally seen in aging cells. In other words, it basically makes them young again. In a study published in 2011, researchers used the OSKM factors to turn senescent human cells and cells from centenarians back into stem cells. The transformation restored the cell's ability to divide many times and differentiate into new types, but it did more than just that. The process also resets the size of the cells telomeres, making them look like younger cells. This study made IPSCs out of cells from people with progeria, a premature aging disease. The reprogramming changed the epigenetic profile of the cells, giving them a DNA methylation pattern like that of young cells. The IPSCs were also able to divide and stay healthy until they differentiated, at which point the progeria symptoms reappeared. The same findings held when looking at a so-called epigenetic clock. As older cells were transformed into IPSCs, their methylation pattern was no different from that of a normal young stem cell. So are the OSKM factors the fountain of youth? Can we just use them to make our cells young and healthy again? Not so fast. It turns out that transforming mature cells into stem cells can have some… troubling side effects. One of the defining features of stem cells is their ability to divide indefinitely, but that's also true over much less desirable group of cells. Cancer cells. This raises the possibility that the reprogramming processes could overlap with processes that cause cancer, which would be bad. Unfortunately, the evidence seems to suggest that it's true. The experiments we've talked about so far were in sole cultures. When researchers induced IPSC formation in mice, the mice developed tumors after their cells began to proliferate abnormally. The DNA methylation pattern also changed in the tumors, suggesting that epigenetic changes might be involved in cancer development. There wouldn't be much point in making someone's cells younger if that also made them more likely to get cancer. It's just not a good trade-off. But there is still hope. Researchers recently figured out how to give mice the benefits of the OSKM factors without the drastic costs. Instead of turning the OSKM factors on continuously, they cycle them on and off every few days. In human and mouse cell cultures, this reversed many age-related changes, including epigenetic features such as histone modifications. When they did the same thing in mice with progeria, none of the mice ended up with cancer or unusual cell proliferation. However still, the treatment increased the maximum lifespan of the mice by 15% and their muscles became better at regenerating after injury. It will take more research to figure out how useful the OSKM factors could be in alleviating aging. Even if that doesn't prove directly useful, studies using them have already shown the importance of epigenetic reprogramming as a tool to deal with aging. Thanks for watching. If you enjoyed learning about epigenetics and rejuvenate itself, give the like button a click and share this video with your friends. And finally, a big thank you to all of the lifespan heroes who make this show possible. Their contributions help lifespan.io support and promote longevity research. If you want to be a part of that, go to lifespan.io slash hero and make a pledge.