 In our previous two episodes on chromatin remodeling and histone modification, we talked about the age-related changes to your cell's epigenome, the chemical markings that affect which genes are active and which aren't. In this episode, we're going to talk about yet another epigenetic change observed during aging, DNA methylation. 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. If you haven't done so yet, click the red button below to subscribe, and don't forget to hit the bell icon and select all notifications. One epigenetic feature is the presence or absence of methyl groups on DNA, which is known as DNA methylation. Methylation changes how DNA is red, affecting the expression of a gene without changing the DNA itself. It's a bit like using tone or font to affect a word's role in a sentence. For example, saying the doctor is here instead of the doctor is here shifts the meaning a bit, though the sentences use the same words. If you whispered the doctor is here instead, that would carry yet a different shade of meaning. In the same way, methylation can silence or activate a gene even though the DNA stays the same. And methyl groups can be added and removed, just like you can change the font of a word. Methylation is a normal feature of your genome. Many genes and other parts of the genome are methylated and the methylation pattern changes in response to stress and other stimuli over the course of your life. It turns out that the DNA methylation pattern in your genome changes as you age. As early as the 1970s, a study showed that as rats age, the total amount of methylation decreased in some organs stayed the same in others and increased in the kidneys. Modern sequencing technologies have given us a much more detailed picture of what's happening. In fact, scientists can now use the methylation levels of DNA to estimate someone's age. These epigenetic clocks are interesting and potentially useful, but that's a topic that deserves a video of its own. Scientists are trying to figure out what to make of the changes in the methylation that happen with age. There are some options, but there isn't yet a clear picture or a sense of why the changes happen. Studies in humans and mice have detected age-related changes that only a small percentage of methylation sites, known as CPG sites, but even if only a few percent of the CPG sites change, there are still hundreds of thousands of CPGs that get methylated or demethylated with age. Most of the changes seem to be sex-dependent. A study in mice found that 95% of the age-related methylation changes happened only in females or males, but that might not matter. The patterns looked quite similar when researchers compared methylation at the scale of genomic regions instead. So, the same genomic elements are changing in both sexes, but the precise CPG sites differ. It's worth noting that that was the only study so far to have looked at age-related methylation in females. Clearly, there is still work to be done. Scientists have also looked for patterns in the methylation changes, whether they usually in certain genes or parceled genome. No consistent picture has emerged, though it's clear that the changes aren't all random. Another puzzle is figuring out the effects of the change in the methylation pattern. Methylation usually regulates gene expression, so that seemed like a good candidate, but researchers have found only a weak correlation between the changes in methylation and changing gene expression in older mice. There haven't been many studies, so it might just be a question of getting more data or better data. Or it might be that the relationship between gene expression and methylation is more complicated, at least in this context. It's also worth mentioning that interventions that slow aging also affect methylation. For example, caloric restriction is a very reliable way of extending lifespan, and it prevented about 35% of age-related methylation changes in mice. Likewise, the drug rapamycin increases lifespan, and it also prevented some of the methylation changes in aging mice. Of course, this might just be a consequence of these treatments' effect on aging more generally. To sum up, it's clear that DNA methylation changes with age and that the changes aren't just random, but we don't know whether they are a cause or a consequence of aging. So while DNA methylation is definitely a useful tool for measuring age and an intriguing topic for further research, we can't say whether it would be a good target for intervention until we know more. Thanks for watching this episode. If you enjoyed it or learned something, give the like button a click and share it with your friends. 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