 The epigenetic program, the molecular switches that turn your genes on and off, is an essential feature of your cells that changes during aging. Your epigenetic program isn't set in stone, so scientists think that undoing these changes might be possible, and by doing that we might be able to reverse or at least slow down the damage that aging causes. In this episode we're going to focus on histones and how aging alters 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 when we publish a new video, click on subscribe, and don't forget to ding the little bell icon too. One epigenetic feature is a pattern of chemical modifications on DNA patterning proteins known as histones. In an earlier video in this series we used books as an analogy for how our DNA is wrapped up in a package small enough to fit into our cells. Histones are like the pages of a book. Just as the text of a book is printed in lines across a page, DNA is wound around histones. Of course, the story isn't that simple. Histones can be modified by the addition of different chemical groups. The modifications are called things like methylation, acetylation, or phosphorylation, depending on which chemical group is added. Scientists also use more precise names to specify the histone altered by a modification, as well as where and what the modification was. One way to think about it is to imagine marking the page of a book in different ways. You might fold the corner or add a sticky note if it's a page you want to find easily. You might make notes about something in the margin. Or if you really don't like what's on a page and you're a bit weird, you could add a drop of glue so that it sticks to the previous page and can't be read easily. The chemical modifications of histones do similar things, changing how accessible the DNA is, and affecting how it gets read. We don't really know the functions of all of the different modifications, but at least some of them seem to be linked with aging. For example, take the modification H4K16AC, which is the acetylation of lysine 16 of histone H4. This modification becomes more common as cells age, which leads to genes near it getting expressed more strongly. The H4K16AC modification is removed by one of the CIRT proteins, which are known to be involved in various aspects of aging. Boosting the level of this protein extended the lifespan of yeast, worms, and flies. But in other experiments with flies, knocking out a different gene that also removes H4K16AC shorten their lives. So once again the picture isn't entirely clear. Another example is the modification H3T11PH, or phosphorylation of 30911 on histone H3. The levels of H3T11PH are regulated by the glucose levels from food, and in turn H3T11PH regulates genes involved in nutritional response. Mutations that disable this modification increase the lifespan of yeast, though it's still unclear exactly what the link with aging is. There are lots more examples, but we're not going to list them all. If you want a gateway into the nitty-gritty of histone modifications, and who doesn't, check out the review paper listed in the description. The review doesn't just summarize over a decade of research linking histone modifications and aging. It also suggests a framework for how the two might be connected. The idea is that histone modifications integrate signals from environmental stimuli, such as diet or stress, in order to control gene expression. In other words, histone modifications are like a communication channel between the changing environment and the static genome. Aspects of our environment that affect aging, diet is a great example, do so in part by changing the pattern of histone modifications. This means that we could potentially increase our lifespan or health span by stopping those changes or finding other ways to control the histone modification pattern. Drugs that affect histone modification are one avenue, but other, easier tools are available now. Regulating diet and other lifestyle habits can affect your histones, changing how genes are expressed, and lengthening your lifespan. Longevity isn't just about treatments to push up maximum lifespan, it's also about the changes you can already make to live longer and healthier. Thanks for watching! If you enjoyed this, why not share it with your friends, and click the like button below. And finally, a big thank you to all of the Lifespan Heroes, whose contributions make this show possible. To support X10 and its parent organization, Lifespan.io, head over to Lifespan.io slash hero and make a pledge.