 It's great that scientists are learning more about aging than finding potential therapeutic targets, but you're probably more interested in things that can help now. Has all this research produced any tools that we can already use to live longer? The bad news is that we haven't found the fountain of youth, or discovered a drug that can stop us from getting old. But there is a simple change that does the trick in lots of different creatures. Chloric restriction. Let's dig in and find out what it's all about. 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. This is part of a series of videos on diet and longevity. In this episode, we're going to talk about caloric restriction. Caloric restriction is basically just what it sounds like, a diet containing fewer calories than normal. In experiments with rats and mice, fewer has generally meant something like half to three quarters of the unrestricted diet. It's important to point out that caloric restriction isn't the same thing as intermittent fasting, which you may have heard about. Intermittent fasting is the practice of fasting for long periods between meals, but not necessarily changing the amount of calories consumed. So, caloric restriction is about how much you eat, while intermittent fasting is about how often you eat. It's also important to be clear that caloric restriction is still supposed to be a balanced diet. The idea is to reduce the number of calories while still providing all the necessary nutrients in the correct proportions. So, what happens if you pull that off? We know that caloric restriction makes lots of animals live longer. It's been reported to extend lifespan in yeast, mice, rats, monkeys, and other organisms, but it doesn't always work. In a study using house flies, caloric restriction actually shortened lifespan, and another study found that caloric restriction decreased the lifespan of mice when it was started at an older age. That's a bit of a mixed bag. From what we know, it's hard to say how useful caloric restriction is for humans. There are some studies showing that it provides health benefits, but there isn't enough data at the moment to draw strong conclusions. We also don't yet fully understand how caloric restriction affects lifespan. There's evidence that it works through several different genetic pathways, which is just a fancy way of saying it's complicated and scientists are still working out all of the details. One of the pathways affected by caloric restriction is genes related to the tor signaling pathway, which responds to nutrient status. To find out more about tor and nutrient signaling, check out our video on the deregulated nutrient sensing hallmark here. Work in yeast showed that caloric restriction reduced the level of tor signaling genes. This made the yeast live longer, but that life extension depended on the activity of several stress response genes. By deleting some of the genes in these pathways and putting the yeast on a caloric restriction diet, researchers managed to increase the yeast lifespan by 10 times. Caloric restriction also causes epigenetic changes. Studies in rats, fruit flies and other organisms have found changes in DNA methylation and histone modifications as a result of caloric restriction. If you'd like to know more about how epigenetics is linked with aging, check out our epigenetics series. The idea here is that caloric restriction somehow helps prevent epigenetic changes that cause our genes to be expressed incorrectly as we age. As though that weren't enough, a couple of recent studies have linked caloric restriction with DNA repair. A 2014 study in yeast found that caloric restriction requires the ISW2 gene in order to extend lifespan. They showed that caloric restriction reduces the level of ISW2, which leads to higher levels of a gene called rad51. Rad51 is involved in DNA repair, leading the team to hypothesize that caloric restriction improves the response to genotoxic stress. That's consistent with a more recent paper, which reported that a brief period of caloric restriction in mice improved their cells ability to repair DNA breaks. So, should you restrict your caloric intake to live longer? Well, the evidence isn't really clear at this point. For example, the NIH webpage says there is insufficient evidence to recommend any type of caloric restriction or fasting diet. It also highlights the importance of getting enough nutrients and talking with a health care professional if you're tempted to try this anyway. That's it for our overview of caloric restriction and aging. Check in again next time to learn about intermittent fasting. If you'd like to get notified about that and stay on top of new X10 videos, subscribe to our channel and remember to click the bell icon. You can also like the video and share it with your friends if you learned something new. And finally, a big thanks to the Lifespan Heroes who make this show possible through their crowdfunding support. If you'd like to become a Lifespan Hero to support X10 and Lifespan.io, head over to Lifespan.io slash hero and make a pledge.