 As we explained in another episode, one of the hallmarks of aging is changes in the epigenetic program. That is, the molecular features of DNA that affect which genes get expressed. Because the epigenome is dynamic by its very nature, it might be possible to undo these changes, delaying or even reversing the damage caused by aging. This is the first in a series of videos we're making about the different kinds of epigenetic features, how they change during aging and how scientists hope to reverse those changes. Today's topic is chromatin remodeling. 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 notified about new videos from X10, click on subscribe and don't forget to ding the little bell icon. One of the epigenetic features is how DNA is packaged into a structure known as chromatin. An easy way to understand it is to think about books. Depending on which book you have in mind, the text would stretch for somewhere between several hundred meters and a couple of kilometers if it were printed in a single straight line. That would be pretty inconvenient and impractical, so we invented things like books and scrolls. And then we arranged the books on bookshelves, which we collect into libraries, storing vast amounts of text and knowledge in a pretty compact form. In the same way, the DNA inside your cells is wrapped around proteins known as histones to make a structure known as a nucleosome. Think of it as a page in a book. Nucleosomes are folded into more complex structures which are wound together to make chromatin. There are still higher levels of organization, such as chromatin loops and chromosome territories, but we're going to stick with chromatin for now. There are basically two types of chromatin. Heterochromatin is more tightly packed, making genes relatively inaccessible while you chromatin is looser so genes are easier to reach. It's a bit like the difference between a book being open on a library table or stored somewhere on a shelf. You can read the book either way, but it takes more effort if you have to find it, take it down, and flip to the right chapter. So, the distribution of u-chromatin and heterochromatin influences which of your genes are switched on and which are inactive. The problem is that this pattern changes as we age. The loss of heterochromatin model of aging was proposed in the late 1990s. The idea is that the heterochromatin pattern degrades during aging, so genes that should be silent become active and wreak havoc. We've since discovered that the picture is a bit more complicated. Heterochromatin doesn't just disappear as we age. It also shows up in new places, so-called senescence associated heterochromatin foci. This leads to instability and means that some genes get switched off when they should be switched on. To go back to our analogy, the library is becoming difficult to use or even getting damaged because it hasn't been maintained. Books that should be easily accessible, maybe dictionaries, for example, have been packed up and put away, and books that should be harder to reach, such as first editions or rare manuscripts, are scattered open on tables. Lots of different factors affect chromatin structure, and one of the things they respond to is DNA damage. If chromatin remodeling factors move to sites where DNA is damaged, but then don't always return to their original location, it might partly explain why the heterochromatin pattern changes with age. In 2009, researchers discovered a link between chromatin remodeling and Hutchison-Gilford-Progeria syndrome. It turns out that the gene mutated in HGPS is involved in organizing the nucleosome. The protein it encodes interacts with other proteins that regulate chromatin, and the mutation somehow causes these other proteins to get broken down. This results in misregulation of the chromatin, leading to changes in its structure and causing premature aging. Another premature aging disorder, Werner syndrome, also seems to be linked to changes in chromatin. A 2015 study found that the Werner protein associates with several proteins that control and modify chromatin. The prematurely aged cells had lower heterochromatin levels and other epigenetic changes. The researchers also confirmed that the Werner protein is lower in normally aged cells, suggesting that the same changes might occur during normal aging. If we could reverse these changes, that is, tidy up the library, or find a way to prevent them, we might be able to delay or even undo some of the damage caused by aging. Experiments with a group of genes called the Yamanaka factors hold out hope that this might be possible, but that's the subject of another video. To get notified about that and other X10 videos, subscribe to our channel and don't forget to click the little bell icon. Thanks for watching, and if you enjoyed this, then please share it with your friends and click the like button below. And finally, a big thank you to all of the Lifespan Heroes, whose crowdfunding support makes this show possible. If you'd like to support X10 and its parent organization, lifespan.io, head over to lifespan.io slash hero and make a pledge.