Dietary restriction and caloric restriction. Is there a difference between dietary restriction and caloric restriction? Yeah, that's a very good point. Because early on in that field, it was always called dietary restriction, it was called dietary restriction. Because they didn't worry about the composition of the diet, they just fed rats and mice less food. Mice lived longer, and stayed healthy longer. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. There was a little bit of early research trying to figure out whether it mattered if we restrict protein or carbohydrates, or lipids. And the conclusions were that it didn't matter, that it was calories that counted. So dietary restrictions evolved to become called calorie restrictions. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. Recently, however, that's been reinvestigated. It's quite clear now that the composition of the restriction counts. We know of cases where even restricting a single amino acid will have a life-extending effect, at least in rats and mice. So now, we're in an entirely new phase where we know dietary composition counts. We now don't even know, we're not even sure of the effect of calories. And I say that because you can feed these animals less. I've been down there in the animal rooms where we have an animal on a calorie-restricted diet. And it turns out that, of course, they're hungry all the time, the animals that are restricted. When you go down there to feed them, they're there, they're just waiting for you. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. And they gobble their food up in a few minutes. And it's only been in recent years that we started thinking about this. What if it's not the calories or the dietary composition? What if this is the fact that these animals are fasting for 23 and a half hours every day, whereas our ad-lib-fed animals are sort of nibbling at their food all the time. And it's sort of refocusing attention on the timing of when we eat. And so there's a whole new area of investigation to investigate the timing of eating. There is now all of these time-restricted feeding paradigms where people will try to telescope their eating into a small period of the day, say eight hours. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. They will fast for the other 16 hours a day in the hope that we can get the same kind of health benefits that our rodents are getting from restricting their diet chronically. Because one of the things we know, the public health community has been telling us for 50 years to eat less. And people clearly can't do that because obesity keeps going up and up and up. And I think a lot more people could do all of their eating within an eight-hour time frame and then fast for 16 hours. I think a lot of people could do that. So to the extent that this works out, and there are lots of variations on this. Should you take your food within 10 hours, six hours? Should you eat just one time a day? What about the timing of eating? Does it matter if you eat in the morning versus at night? These are all active research questions that are being worked out. They're being worked out in humans because laboratory mice are just not very good at this for a whole variety of reasons. For one thing, they're active at night. For another thing, they are laboratory mice that have lost a lot of the rhythms, the body rhythms that we have. They don't make, for instance, melatonin in their pineal glands like we do. And so this is a really exciting new area o research. It could be that dietary timing patterns that are being discovered now will continue to be refined in the coming years. They will say, you can eat what you want, but you have to do it on this schedule. That's something that could revolutionize health. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. And in a way, we don't have to wait for drugs, and it could be implemented almost immediately. You also showed that 10% caloric restriction leads to almost as much of a lifespan extension as 40% caloric restriction, but it does not apparently lower cancer risks. So there is a dissociation probably between cancer as a 'standby' for other diseases. But at least if we talk about tumors and the age span. What does it tell you as far as the application in humans? Well, that's an interesting point. And it does bring up a very interesting point that comes from one study of one sex of one genetic strain of rat. Now, whether that's a more general phenomenon or not, we don't know yet. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. The thing that makes it of interest is now they've tried several different dietary restriction studies in humans. They've tried to restrict humans 25% of their caloric intake. They have failed at that. Even with a lot of counseling, all people cannot do that long term. People could only restrict their diet by about 10%. So if you can get the health benefits by restricting the diet by 10%, many more people could do that, potentially. However, we don't know if this is a general phenomenon. We also don't know what to make of this. Are we talking about obese people eating 10% less and then becoming less obese? Or people who have a normal healthy body weight, should be eating 10% less, and becoming exceptionally lean? Don't we know which of those two paradigms is the most consistent with what we've learned from the rodent work? Oh, this is very interesting. These are the practical questions for people. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. And I hope we'll be able to learn more about them as time goes along, and hopefully soon That's a big difference in how one's lifestyle and food consumption and patterns of life influence aging. Right! You're right. Dr. Steven Austad, PhD. Dr. Anton Titov, MD. I think the public, the general public, is starting to understand this because a signature event of the 21st century will be the unprecedented aging of the human population. And we want the aging human population to be as healthy as possible. So these things are very important at every level of society.