From questions about protein intake to the effectiveness of certain drugs on circadian rhythms, DOC 2025 Faculty members Dr. Tony Masri and Dr. Valter Longo explored the bedrock of longevity during their session “Fueling Longevity: Nutrition and Sleep,” moderated by Nora LaTorre, CEO of EatReal.
After their individual talks, Dr. Masri on optimal sleep habits and Dr. Longo on fasting and caloric intake, DOC participants dove deeper into their research, with questions pointed at how to apply their guidance with patients.
For example, despite the current social media hype about increasing dietary protein, Dr. Longo, the Edna M. Jones Professor of Gerontology and Biological Sciences and the Director of the Longevity Institute at the University of Southern California-Leonard David School of Gerontology, reiterated that protein-restriction, more so than calories, can “extend the lifespan of any organism,” he said. Dr. Masri, neurologist and co-founder and CEO of Helyx Health, addressed queries on how to combat jet lag, including melatonin, modafinil, and particularly, magnesium.
“Placebo effect is a real thing,” he says. “If it helps you feel better, great. But it doesn’t solve any medical problems like insomnia and such.”
You can hear more from the full session in our video, or read our lightly edited transcript below.
TRANSCRIPT:
Nora La Torre
This morning we’re going to be talking about fueling longevity, nutrition and sleep. These are two of my favorite topics. As you know, I am deeply passionate about nutrition. I’m obsessed with sleep. I’m so excited. And these are two of the most cornerstone topics for longevity. We are so lucky today to have two of the top experts on sleep and nutrition with us. I want to just dive in. If you could come to the stage, do you want to if you could each take a seat here, please? Let’s welcome them.
First we’re going to eat and then we’re going to sleep. Wwith that we have, D. Valter Longo who’s going to be sharing about nutrition specifically about, the effects of nutrition on aging. We have, Dr. Tony Masri, who is going to be talking to us about the fountain of youth is in the bedroom. More conversation about the bedroom, as you heard from his colleague yesterday, in the I think we’re now calling the, Sex, Rock and roll. Part two of that talk, but more cornerstone of the bedroom. We’re going to do is do just two quick lightning talks, and then we’ll have a dialog. We’re going to try something a little bit different in this dialog. We’re actually going to have the speakers ask each other questions. I think that will be really fun. I have been so excited about this. I have my own Nora questions. We’ll do a quick round of that, and then we’ll open for some Q&A for all of you.
As the questions come up, think of them, then we’ll ask you to go to the mics afterwards. So, let’s eat. If you want to start with your presentation that would be incredible.
Dr. Valter Longo
If you look at 100 years of longevity research, calorie restriction, which is something very simple, it’s actually if you take a normal calorie diet, and restricted by 25%, the calorie station turns out to be the most successful intervention, I will argue ever to slow down aging but also, combat diseases. The first study on human calorie restriction was done by Dr. Roy Walford, the bold guy at the bottom of the picture. Roy was a medical doctor at UCLA. He was my boss, back in 1992, 93. Roy decided to do the first clinical trial on human calorie restriction.
He locked himself up in this Biosphere 2 area in the desert of Arizona near Tucson. For two years they did a calorie restriction study. So they just reduced calorie intake by 25%. They also had a very healthy diet. But that’s not the ideal of caloric restriction, right? If you look at systolic blood pressure, they’re fairly healthy. A group of eight people, systolic blood pressure drops from 110 to 90. Glucose from 95 to 70. Cholesterol from 185 to 125. You can look at this, and if you’re a cardiologist or a doctor, you say this is great. Then you look at Walford on the left when he came out of Biosphere 2, and you say, if you’re a doctor, this is not so good.
It’s being pushed to the limit. The question is, how do you keep all these incredible effects of calorie restriction really revolutionized medicine, right. If you could change cholesterol, blood pressure and not just inflammation. This calorie restriction really goes after almost anything that you can think of that is bad for you. But it comes with a big cost, including lean body mass loss, bone density loss, potentially immune system. Certainly, dampening of certain functions of the immune system.
Back then, I start thinking how do we keep the good effects of calorie selection without the bad that I just mentioned. So first, I started thinking, can you intervene for just five days, let’s say a fasting once every month or two months or three months and that’s it and then let the person go back to their normal diet. Then can we do it now with water-only fasting. Can you do it with a fasting mimicking diet. That’s where I, thanks to the funding by the NIH, develop a low calorie, low sugar, low protein, high fat, vegan, five day long fasting mimicking diet and without going through the markers.
We are looking for fasting response or response to four markers IGF one, IGF, VP1, glucose and ketone bodies.
The first trial was a USC, 100 patients randomized crossover. You see the on the right is the result after three monthly cycle of a five-day fasting making diet. It’s a major reduction in weight, abdominal fat, waist circumference. But unlike the GLP-1 receptor agonist drugs, you don’t see the absolute lean body mass loss. You see that muscle is preserved, maybe a minor loss, but muscle is preserved. These cycles of FMD are targeting fat without affecting negatively the muscle mass and the bone density also.
It’s interesting differently from the calorie restriction. If you look at just give you a couple examples, glucose in normal subjects there’s a small reduction in glucose. But in pre-diabetic subjects, most pre-diabetic subjects now go back to the normal range. So it’s differential effects which were not seen by calorie restriction. Same thing with cholesterol, with cholesterol below 200, relatively normal, they have a decline after three cycles. The FMD keeps going forward. And those that have, hypercholesterolemia, they have a much larger, benefit after of the three cycles of the FMD.
Now, Heidelberg did actually a trial that on diabetes patients. They compare five days of a Mediterranean diet with five days of a fasting, diet, thinking maybe it’s just a healthy diet if you do once a month, a healthy diet for six cycles, six months, you’re going to benefit.
But as you can see, no effects of the Mediterranean diet on A1C, but also no effect on insulin resistance. But there is a a major, reduction of B1C 1.4%, also a major reduction in insulin resistance. And the most important is diabetes drugs in hypertension, drugs. The FMD is able to allow 70% of the patients to reduce drug use, either the dose or completely get rid of drugs. This is not seen in the Mediterranean diet where you actually see 30% of patients increase the use of diabetes drugs.
Why do we see these effects on hypertension? As I showed you earlier, with even calorie restriction, lots of effects and lots of different systems. We started looking at cellular reprograming. We knew that there is cellular autophagy occurring after fasting. We had shown the stem cell are increased, but we are also very much interested in this reprograming this is probably the hardest thing in aging research, right? Can you turn on these Yamanaka factors and all these embryonic developmental factors and make an old cell young? This is what is now being done by biohacking, by lots of different methods.
A few years ago, we published this paper where we damaged the pancreas of a mouse. You see, in the left at the bottom, you see that red is insulin producing beta cells. Then you see what is D5, a lot of the red is gone. Day 50, it’s permanently gone. We now damaged the pancreas irreversibly. But now after irreversible damage to the pancreas, we start with the cycles of the fasting making diet. You see that? The right, the pancreas goes back to normal. It’s making the insulin producing beta cells are regenerated, and the insulin is produced, and now the hypoglycemia here, comes down on the left up. Why is that? It turns out that you see those, three columns. The first one is the mice are eating normally. The middle one where it says FMD is at the end of the four-day fasting, mimicking that in this case, for mice. You see all these red, red colors. It means that the embryonic developmental genes have been turned on. Now including Yamanaka factors, in a coordinated way, the fasting feed cycles are turning on these regenerative, embryonic developmental, genes and repairing. Now is this systemic or is it just a few organs? We’ve shown for the gut, we’ve shown and for the kidneys we’ve shown it for the pancreas. In collaboration with Morgan Levine, who is now out of the lab, we looked at biological age, what happens after three cycle of the fasting week, diet monthly FMD. It turns out that, People become two and a half years younger at least according to these blood markers, which include cholesterol, blood pressure, A1C-reactive protein.
To the FMD, which is at the very bottom, let’s say one to three to six cycles or so of FMD a year, depending on who you are. Then I wrote a book called “The Longevity Diet,” based on lots of different, parts of science or fields of science, including epidemiological studies, centenarian studies, mouse studies, you know, areas of the world, where people have record longevity. So it’s mostly plant based, plus fish 3 or 4 times a week, low protein until age 65 to 70 and then moderate after lots of legumes, whole grains, vegetables, healthy fats, no red processed meat, low eggs, low sugar, low refined grains. These up to age 65/70. Then most people need to expand. And we think the Mediterranean diet now becomes maybe a better option, just because it’s safer, it’s more nutrients. And so Longevity Diet into 65 then I mean during and after, wine three a week. Fine. Three glasses a week. High nourishment. Eat within 12 hours a day.
A lot of you have heard about, the 16-hour intermittent fasting. It’s a bad idea. We can discuss it later if there are questions about that. But the 12 hours is certainly a very good idea. Not a negative study I’ve ever seen. It doesn’t work as quickly as 16 hours, but it’s much better option, a much easier option. And then if overweight, we recommend we follow a lot of patients in the foundation clinics. We recommend, two meals, plus a snack until you go back to normal weight, and then you can resume your three meals process snack. Thank you.
La Torre
We’ll dive into questions in a moment. I so appreciate that you’re challenging some of the current crazes to around, protein and intermittent fasting and offering a different path. Now let’s sleep, so let’s hear from Dr. Tony Masri.
Dr. Tony Masri
Sleep. The fountain of youth is in the bedroom. This is actually a quote from, Bill Damon at Stanford, who discovered REM sleep and started the first sleep clinic. Does anyone know this artist. No art history majors here? It’s kind of obscure. On the right, this is, William Blake, “Jacob’s Ladder.” from 1800s, depicting Jacob lying down, sleeping, and then the angels going up and down stairs. Then we go back to the other one on the left. This is very much the oldest, painting or the oldest cave art that we know from humans back 44,000 years ago in Indonesia. What it depicts is, depicts a creature that’s part human, part animal chasing wild pigs. What anthropologists tell us that the first time humans really started thinking or realizing that they can be outside of their body and look at themselves in a 3D fashion, was through dreams.
When we sleep, we discover things about ourselves. Sleep has been teaching us things about ourselves, from the spiritual to our physical well-being, to our mental health, etc. and the extent that sleep tells us about our state, our wellness, our disease process, what’s happening with us is the extent that we can measure it, and to the extent we can be curious about it and our tools and technology.
Over the years, we we’ve been observing people sleep ever since the dawn of humanity. We start out with observation. Clinically we know, for example, that, Cheyne-stokes, discovered by watching patients who have heart failure, in the middle of their sleep and seeing these agonal breathing. Then we fast forward after that in 1924, Hans Berger was a German psychiatrist, used the first EEG on humans and saw the squiggly lines and scribed them as alpha waves and beta waves. Interestingly was a psychiatrist. Then about ten years later, another researcher Nathaniel Kleitman, who was very influenced by the work of, Freud, decided to study sleep as a way of understanding human consciousness, and then came to New York and later on to the University of Chicago, and became the first full time researcher dedicated to the understanding of sleep, sleep, physiology, etc., and was very much into it.
He spent a month in a cave underground. He fasted for several days. He kept meticulous notes of his daughter from the time she was an infant until she was 20. He was super dedicated to that and he was using basically, he took that EEG from Hans Berger and then he would record patients’ EEG throughout the night. For every night, it would be about a half a mile of paper recording for all these squiggly lines, almost as long as a CVS receipt. So then came Bill Dement, who was one of his mentees, and they worked together and they discovered REM sleep. Bill Dement went on to Stanford to establish the first, sleep clinic. And then we start understanding sleep quality. We first start looking at sleep quantity, then sleep quality. That probably some engram showed up. Then we started looking at what happens when we sleep. We discovering diseases like sleep apnea. We understood the impact of sleep apnea and cardiac disease. And as our technology improved, then we started unraveling ideas and understanding the timing of sleep. We fast forward to data population in the last, 10, 20 years, which tells us a lot about timing.
First I’ll start with quantity of sleep. Everyone asks, What’s the exact time I need to sleep. What’s more important is are you sleep deprived? How many people here use an alarm to wake up in the morning? Less than I thought. If you’re using an alarm in the morning, you’re not getting enough sleep. That’s a better way to ask that question. If you’re sleeping in on the weekend for more than an hour, you’re not getting enough sleep. So what does the data show us? When we look at a meta analysis, for example, from 2010, they looked at 1.3 million people and looked at, longevity. If you sleep less than seven hours, your long term risk of mortality goes up by about 12%. If you sleep more than nine hours, then your, longevity is impacted by all risk mortality goes up by 30%. You know, I said 24% last, it was actually 30%. So sleep. As much as we want to sleep to be better and have better longevity sleep, it also can tell us as a sign about what’s happening.
This is a sleep wake cycle. This is what we call that a hypnogram. Before anyone pulls their, wearables starts comparing, no one looks exactly like that, the same way no one is exactly at 120 over 70 pressure all the time. So there are variations, that are normal variations. But what that tells us is primarily that you get more deep sleep the first half of the night, you get more REM sleep the second half of the night. We used to think that you only dream during REM, but you also dream during deep sleep.Instead of having vivid, colorful video like dreams, you know it’s black and white and pictures.
What happens when we have poor quality sleep? Looking at a large data set of about 300,000 people, with a group of 150,000 of them where we were able to match, primary care data, whether there are other diagnoses, patients who reported poor quality sleep, they just felt that they’re not refreshed, they scored high on sleepiness scale, they were had two years less of cardiovascular free years. Some of these cardiovascular events, about 20% of them, led to death. Those who had sleep apnea had about seven years less of cardiovascular disease free years. So it’s not just a matter of mortality. It’s a quality of life and complications. For insomnia, four years. The data was mostly consistent between men and women. So it’s very important.
The other data set is from Emmanuel Mignot, he looked at probably one of the largest data sets of patients who come in, get a blood lab, does a detailed questionnaire. He shows that about 5% reduction of REM sleep increases, mortality by about 13%.
This is one of my favorite, slides here, and it shows I know if you have the last slide said, but this is from, Brian Murray in Toronto, where they did something interesting. They went and looked at normal controls. We used to think that when patients get older, basically, you start having poorer sleep, you wake up more often, your sleep actually is reduced. But in reality, what they did in this interesting study, they went and looked at all the normal controls from various studies, They were able to pull 5000 normal PSGs (polysomnography), which are actually rare to find. They said, how does our sleep change? What I love about this study is it changed our thinking in the last ten years. We actually found out that on average, we sleep about ten minutes less every decade, starting from our 20s. So when you’re when you’re 40, sleepy about 20 minutes less. When you’re 60, it’s about 40 minutes less. However, at the same time, you’re amount of deep sleep and REM sleep as a percentage, which is usually about 20 to 25%, does not change very much.
As physicians, it’s important for us to ask the question if our patient is sleeping, or not sleeping as well as they get older, it doesn’t mean that they’re just older and we ignore it. We need to look for underlying causes that can cause them to have less sleep. We really pay attention. Where I look first is I look for typically sleep related diseases like sleep apnea, periodic movement, restless legs, insomnia, etc. The next thing we look at in non-directly sleep related conditions like depression, mental health, chronic pain for example, hormone changes in women. Then you look after that for wellness. Is your patient exercising enough? Are they eating well? Is their sleep wake cycle consistent?
The next study here. So I told the importance of quantity, qualities. Even more important than quality. This is a very interesting study looking at, about 60,000 patients or 10 hypnographies. Now we’ve gone from observations and not population data, and they looked on average about a week. Regularity, having a regular sleep wake cycle is actually just important., not just as important, more important than getting enough sleep. If you look here, the white the three white boxes, if you are the most, if you have the most irregular sleep wake cycle. Now you can actually look at your wearables. So at the bottom of the X axis is the timing in each of these black bars is this day. If you’re going about a different times at different days, the more irregular that is you can increase all-risk mortality can go up by as much as 40%.
Speaking of AI, I asked AI to make a basically an art piece. Summary slides. I took the slide from the previous study, fed it in it, and I was like, make me a slide. You can see the art here. I actually tried several of them. Not exactly the best art. So can AI really tell the story?
Take homes. We cannot achieve optimal, health span in lifespan. Obviously, without optimal sleep. Problems are common. Universal, more or less. But the solutions are unique and tailored. You can have apnea, insomnia, you can have disrupted sleep like everyone else. But the solutions should be individual and personalized for every for every patient. And then best sleep is organic. Your bedroom should look the same as it looked hundreds of years ago, and then you have to be very deliberate about what you bring back in, whether it’s technology, TVs, obviously we’ve determined that’s not good in the bedroom. Having, natural fabrics, seeing the temperature change naturally, that ultimately will lead to, best sleep.
La Torre
I love the DOC community. I am already counting down to 2026. I’m sure many of you are. I love the brilliance in this room. I love the extreme generosity that you have with one another, and I especially love the curiosity. So right now we’re going to get curious about these two topics and these lightning talks that we just heard. But first, I’m going to ask our speakers to get curious with one another and ask each other questions about your talks.
Longo
I’ll start. So I am curious for all the patients that we follow, about temperature in the room and light in the room, there was an article that just came out that said even a little bit of light can disrupt your sleep. Is that what you have experience and seen?
Masri
That goes back to my last notion about organic sleep and organic setting. If it’s bright, if it’s not an organic light, you have light in the room. Obviously you want to be safe. If you were to have a light, you want to have something on the red spectrum in the room. As far as temperature, typically lower is better. We quote a lot in like, low 60s, mid 60s. But what’s really more interesting too, we’re finding out, is the changes in temperature is also important. It’s coolest in the middle of the night, and then as the morning rises temperature can get warmer. So ideally if you’re in the Bay Area you’re lucky, you really don’t need heat or air conditioning most of the time, and then you get this opportunity to see the changes in temperature.
La Torre
Do you have questions about nutrition?
Masri
I have a couple. We hear about the Mediterranean diet. And sometimes it’s hard to define it. I see you have dark chocolate there which I love. Fantastic. That’s great. But what’s your advice when people talk about Mediterranean diet. And then how do narrow it down a little bit, as a busy clinician, you want to give a couple recommendations for patients.
Longo
This is why I came up with the Longevity Diet, which of course learns from the Mediterranean Diet, from the Okinawa Diet, from the Loma Linda Diet and from lots of other things, and puts it all together in the common denominator.
I think this idea that the whole world should eat the same as the Southern Italians did, 50 years ago is probably not a good one. We hardly find somebody that does not have intolerances, allergies, somebody gluten and tomatoes, and lots of things. I think the idea of the Mediterranean diet is an old idea. We learn a lot, and that’s the great thing, is that there are so many clinical trials on the Mediterranean Diet. We can we can use those to then move to the next level more personalized, and it doesn’t have to be complicated because people would think, “Oh, this is very complicated as a manual for eating,” or that’s not the case.
But lots of people have problems. To live to 110 healthy, it’s extremely difficult. A lot of things that we have to follow, and in the Mediterranean diet, we know extend your life by about 10%, but that’s not what we want. We would like from 80 to 88. Probably the Mediterranean diet can achieve that. But, to go to 110, it’s a not a given.
La Torre
I so appreciate that. There are core tenants in both sleep and nutrition that we can all apply at this personalization that’s necessary, and based on where you’re from, your cultural preferences, etc. I see a lot of curiosity in the audience. Let’s dive in with audience questions. Would you like to go first, please?
Audience question
I’ve got so much curiosity that I have one question for each of you, by the way, I thought the sessions are amazing. So my question for Valter [Longo] was one of the things that I think is different in your point of view versus the general literature and the kind of popular opinion right now is about protein, because what you said, low protein up until the age of 65, I think going after that moderate protein. I’d love to know more about that, because if you’re like me and like everyone in my environment, we just talk about how do we get more protein. It’s literally that how many shakes, all that stuff. The next question is for Tony [Masri], we travel a lot. I think everybody in this room, I mean, has traveled to be here, and we were traveling a lot. So given the importance of sleep regularity and how that’s even more important than duration, how do you suggest we handle it when we’re in different time zones. And the body wants to sleep later, even though maybe the circadian rhythm wants us to wake up earlier and our, you know, our regularity is totally off. I’d love to know your point of view.
Longo
Proteins, I should have added sufficient low but sufficient, which is 0.8g/kg per body weight. So about 0.37g per pound of body weight per day. Right. Which is fairly low if you look at all the podcast and all of that is so, it, it comes from the Okinawans had very low protein diet. The Italians now they have record longevity. They have the low protein diet. The Japanese have a low protein diet. The monkeys, they live longer. The mice. The rats. I mean, it doesn’t matter where you look at the one thing that you can the one thing that you can do to extend the lifespan of any organism if it’s not calorie restriction, is protein restriction.
But it has to be sufficient because otherwise you go from one problem to the other. Now you become malnourished. If it’s too low and even if it, it can be 0.8. But if it was mostly legumes, legumes have a very little, essential amino acids, methionine, leucine, etc. This is why it’s good to have a nutritionist, you know, even if it’s once a year or twice a year, then knows what they’re doing because then they can adjust and say, “Okay, this is your diet, you’re vegan, for example. Okay, fine.” But then you need to know certain things and you need to eat a certain way. So three fourths of the proteins can come from legumes. So they can be 0.8. Otherwise they have to be 1.52 per grams per kilogram, because you’re just getting legume, amino acids. Right. So a little complicated. But once, you know, it’s very easy to follow.
Masri
With jet lag, obviously a very common problem I go over that was a lot of my patients. You have to mitigate the impact obviously. In the theme of common problem, there are unique solutions or tailored solutions. What you can do. One is that you can fast. So fasting, because our gut biome is a bidirectional relationship, when we eat we get a signal to our circadian rhythm and vice versa. So you can fast certain times you can usually about 15, 16 hours before your destination. You want to sync, you want to eat basically, at the local time. Our bodies have these signals about resetting our circadian rhythm and eating is one of them.
Light is the strongest trainer of all, strategically get light. The general rule is within 15 minutes of waking up to get about 40, 45 minutes of being outdoor. If you can help it, there are light glasses to kind of expedite that process. Melatonin can be helpful, but when you take melatonin, it’s actually micro dosing melatonin, when you take it compared to when you’ve left to the destination is really important. The best you can do is actually speed up the process of where you are. Social activity is a big contributor, but oftentimes you don’t have any control over that because you’re going to be with other people. So that’s your general idea. Inflammation can be also part of it. So sometimes managing inflammation. Staying hydrated is important.
La Torre
Those are great tips. I also am being Instagram added about more and more protein. And I travel a lot. So I wrote down some of those. Let’s hear from the side of the room.
[Audience member]
Hi, it’s Michael Castro, oncologist. I wanted to thank Valter for his work because over the last ten years, I’ve seen many patients on chemotherapy use FMD to improve their resilience and tolerance of treatment. It’s palpably different to manage toxicity in the clinic. But I’m concerned about the Yamanaka factors. I have two questions. One is, is there a difference between water fasting and FMT with regard to inducing stem cells? And is there a timing issue with the risk of inducing a cancer stem cell? And the problem is we can’t kill cancer stem cells with any therapy at all. And so, it seems from my podcasting that the stem cells come out around five days, so it should be okay. Right? But on the other hand, we have this worry about what is the timing. How long should people fast if they’re on chemotherapy and that sort of thing?
Longo
I think that, first of all, the fasting alone, we’ve looked at cancer stem cells and they usually decrease.There are rare occasions it is a work at MIT, where you combine the fasting with induction of certain factors for colon cancer and the combination, which is a very rare, situation, increases cancer stem cells.So far we’ve seen cancer stem cells go down. So normally stem cells go up, and cancer stem cells go down.
Water-only fasting. We this is why I developed the FMD because we tried we had the trial and, water-only fasting back in 2011 in the Norris Cancer Center. Nobody wanted to do it, the water-only fast. The cancer patients did not want to do it in. The oncologists were worried. I think we moved away for lots of reasons, safety reasons, hypertension, hypoglycemia, etc. we moved away from where only fasting only do FMD. Now there’s I think about 15 or 20 trials that have done FMD and cancer treatment. The trick is timing it, right with immunotherapy hormone therapy, chemotherapy, radiation. So in each case we time it very differently sort of thinking about the molecular biology and the cell biology behind it.
But we’re happy to talk to you, about those details. Also, I just published, a new book called “Fasting Cancer,” and it talks about all the trials and all the work that has been done by many laboratories on this.
La Torre
Thank you so much for your work on that. We have a few minutes left. If we can kind of go deep and brief on the questions and then debrief on the answers, we can get through as many as possible. Because I want to hear your questions as well. If you could go ahead please.
Audience Member
I’m Rachel Sarnoff, I’m an internist at UCLA and a gut brain specialist. My question is for both of you. I am curious, Valter, I wanted to hear your talk or your take on the shorter fasting windows because 12 hours, which is what you recommend in the slide, seems quite long to me, like 8 a.m. to 8 p.m. of eating throughout the day. I would love to hear how you square that with the research on intermittent fasting with an 8 to 10- hour window. Then also how both of you think of that in terms of eating close to bedtime. Especially in terms of sleep and having our body kind of already have digested our dinner, how important is that to have, the window of time between the last meal and when we go to bed.
Longo
People now eat for an average I think it’s published about nearly 15 hours, eat. That should go back to 12. That’s it, right? It shouldn’t be any less than 12. So people should eat for 12 hours and fast for 12 hours. I would not do the longer. Fasting is not necessary and as I mentioned, is associated. I think I mentioned that we were talking about earlier, but it’s associated with lots of problems. One of the reason is cholesterol keeps increasing in the human body, as you fast past 12 hours. Now data suggest, increase or almost double cardiovascular disease for those that fast for 16 hours, and skip breakfast. About sleep, our recommendation is keep it three hours away from sleep time.
Masri
I agree exactly. You don’t want to go to bed hungry, but you don’t want to go to bed on a full stomach. That’s what I tell patients. But three hours is a pretty good rule, in general.
La Torre
I follow about the 3 to 1 methodology three hours before bed. You stop eating two hours, you stop drinking wine and minimal drinking, especially wine and just drinking water, two. Then, one hour, no screens.
Masri
That seems right, a good way to remember
La Torre
Let’s hear from Mr. Longevity himself. Dr. Verdin.
[Audience Member, Dr. Eric Verdin]
This is a question for, Valter. I agree with you in terms of protein abundance in the diet and the current craze that we see in terms of people, you know, pushing proteins, I really do worry, especially, on the basis of your work on IGF one and risk of cancer and so on that. I don’t know where this craze is coming except that’s the latest one. I also agree that after 65, I mean, there’s recommended for increased protein intake. One of the struggle that I have talking to people about this is how do you actually assess, sort of measuring everything that you eat, which is pretty difficult, although there is software, do you think IGF-1, plasma levels is a good surrogate marker of you average protein intake, or if not, what else would you use? Y
Longo
Knowing about much proteins and where it comes from per day is I think it’s pretty straightforward if you put some effort into it. But otherwise, you know, we publish on our meta analysis 120 to 160 IGF-1 is a good general way. Whenever we see patients that have 65 IGF-1, that’s usually male nourishment of some kind or some disease at the base of it. I think that 120 to 160 IGF-1 is a good way to at least initially assess. But also making sure that somebody has the right type of protein daily. That’s why I would say fish 3 or 4 times a week. If you have a fillet fish 3 or 4 times a week plus plus, it’s difficult to get malnourished. But if you have it instead of once a day you have twice a day, it’s easy to become protein. Have too much proteins in your diet then. This is what happens to children, by the way. And this is probably why children in now may have 2 to 3 times more protein. The recommended by pediatricians. Because they go to school, they eat proteins, they go home, they eat proteins again, they eat meat. So that twice a day meat is probably, contributed into this, phenomenon.
LaTorre
Interesting. Where we have time for one more question. Oh, I’m getting time. Thank you.There are a lot of folks with questions. Please.
Audience Member
I work in the environmental toxin testing field. And my question for you, Dr. Masri, is, how do you think about what are your perspectives on and what are the data on other possible effects in, factors of sleep around, ppm concentration, VOCs, the material that we sleep on in our mattresses is carbon dioxide. Some of the other things. How would you suggest people weigh the balances between, approaching those and then all of these other things that you’ve talked about to support sleep.
Masri
Kind of the general rule, again, goes back to organic, healthy in terms of synthetic fibers, and what is breathable. There’s a talk yesterday about menopause. And pollution is bad for you in general. Pollution raises the risk of cancer among other things. There are some wearables, in the past that tracks the pollutant in the air. That’s going to be helpful. That’s where you manage your basically the environment, as much as you can, but generally it’s the same thing applies in general, anything else.
La Torre
So don’t sleep on the side of VOCs and formaldehyde and try to answer sheets. These are some of my questions.
Masri
Most synthetic things should be outside the bedroom. Again. Think of it like an organic framework.
La Torre
I know we both have children. So I’m obsessed with like, okay, what’s in their pajamas? What’s in their sheets?
Masri
What’s in there, what’s in their sheets, what’s in them, what’s in their mattress, the temperature, how breathable it is.
La Torre
Thank you.
Audience member
I’m a medical oncologist. First, I’m based in Singapore, so I’m kind of screwed on the jet lag. But your thoughts on Modafinil for jet lag and shift work in general? If they don’t know Modafinil, explain what it is. But the second question, as breast oncologist with lots of hot flashes for our patients, young patients, older patients, classic menopause problems, plus chemo, what’s your advice for managing hot flashes that disrupts sleep without using pharmacology?
Masri
Yeah, that’s a great question. So, first the Modafinil, Provigil is the brand. It’s basically, not a traditional amphetamine-based stimulant. It’s the best way we understand it affects dopamine pathways. It’s fairly safe. It’s been around for a very long time. It’s now generic. It’s FDA-approved for jet lag. And they do use it. It’s actually been used off label for a lot of other things, but it’s a good choice.
You kind of have to, advise patients a little bit about headache. We you should think about Stevens-Johnson as a risk factor, that we don’t really see that very much. So that’s a safe choice. As far as hot flashes, I thought you were gonna ask me not a prescription. That’s an easy answer to that. Because we’ve seen some benefit with Gabapentin, for example. It’s cooling room. It’s cool. Again. Breathable fabric. Temperature being cool in general. If there’s. This is where some areas where, having some technology in the bedroom, keeping it cool because of that or actual mattress can be helpful. Anything that can, mitigate the changes and the hormone therapy, but I guess that’s not my place.
La Torre
What about cold showers or cold before bed if you don’t have temperature regulation. Does that help with that?
Masri
You can. But also we’ve found out that warm temperature, like a hot tub or shower, warm shower, increasing that temperature, then it drops later is actually helpful. That can increase your deep sleep. So there’s an argument for that.
La Torre
Wonderful. Thank you.
Audience Member
You talked a bit about medication right now, but I’m curious to get both of your points of view on supplements. I know there’s a lot of, talking about Instagram crazes. Lots of content out there about melatonin and magnesium, all these things for sleep. Obviously, we’re all hoping to supplemental nutrition and offset all the bad stuff we eat. I’m really curious to get both of your points of view on that.
Longo
My recommendation, most of the trials on supplementation have failed. Very few supplements in any area have shown to even extend the lifespan of a mouse. My recommendation has always been, and deficiency a lot of people are deficient, whether there is vitamin D3 or B12. I think if there is a risk of deficiency or proof of deficiency, then definitely, the supplementation, should be there. And specific uses of melatonin, obviously. And Tony can answer that.
Masri
I agree on the deficiency side, you hear a lot about magnesium. There’s some supplements that B9 like magnesium. Placebo effect is a real thing by the way. Not only it can help us, it can change sleep architecture. If it helps you feel better, great. But it doesn’t solve any medical problems like insomnia and such. Melatonin can be very helpful. I use melatonin quite a bit for resetting the circadian rhythm. It is safer than the hype out there. It’s a lot safer. But like anything else, you have to weigh benefit risk. You don’t want to take it just to kind of feel better. But melatonin has been shown, especially with neurodivergent kids who suffer from anxiety or autism, there’s a really good data on using melatonin in children in long term three milligrams or over several years. If the kid is getting an extra half an hour or even of sleep, then it’s worth it.
La Torre
Thank you.
We have time for two more questions really quickly.
Audience Member
A really quick question for Tony. And a question for Valter. For Tony, the standard of measurement and time is sleep. Is it consistent? Meaning is it a wearable, time asleep or is it a time you close your eyes to time you wake up? Because there’s a there’s a difference between measured sleep by wearable versus what you used to consider time of sleep. Then for Valter to talk quickly about vitality versus longevity.
Masri
Sleep, that’s a very common thing because there’s such a thing on one extreme called super wake misperception, where people completely cannot fully, assess whether awake or asleep. But for most of the time, I’m fine with subjective reporting, when I give patients sleep diary, especially with insomnia, if you think you are asleep, let’s write that down. We can measure it. Wearables are helpful in some cases to see which direction you’re going, kind of like an accountability partner. But generally speaking, both I used subjective and, and some wearables in my clinic, mostly subjective reporting.
La Torre
I think he was also asking, like, if you recommended 7 to 9 hours
Masri
The recommendation is seven, closer to 7 or and a half.
La Torre
Do you count time to sleep and then or time asleep? A window to be in bed.
Masri
You can give yourself eight and see if you can get seven because it’s not abnormal to take 15 to 20 minutes to fall asleep. It’s not insomnia. If you’re a certain age group, being up in the middle of night for ten minutes is not abnormal. An important tip, and you probably mentioned this later. You only should go to bed when you’re sleepy. That’s the general rule. Not when you’re tired. You want to avoid your spouse and that when you have pain. Not when you solve your problems. You only go to bed sleepy. So if you set off a set wake up time, which is really the key, then you’re going to get sleepy about 7 to 8 hours prior to that. That’s really going to anchor things.
Audience Member
Seven hours at a time. You go to sleep, you’re receiving sleep for seven hours.
Masri
Objectively, I’d love to see seven.
La Torre
With a wearable as measured by one?
Masri
Both to some extent. The wearables are not, I mean, t there’s some that can be off too. If you can use your wearable and it’s telling you you’re sleeping more than 7 hours or 7 hours plus.
Longo
So let me answer is about vitality. So there’s two words. One is health span. So of course, a study by Harvard suggests in only get to 70 healthy. Almost everybody has chronic diseases. So health span is the most important thing. And then I introduce a word which is called juventology and youth span. So can you stay younger, longer. AI think that that we need to treat aging for that. Instead of only treating diseases we need to treat aging and keep the biological age, lower and lower or as low as possible. That’s the only way to, to affect vitality and youth span.
La Torre
Final question, please. Thank you.
Audience Member
On a slightly different topic, so maybe good that it came last. You made a kind of a throwaway comment about the hottest thing and longevity research being partial epigenetic reprograming, which hasn’t been a topic that we’ve really heard much about here. Full disclosure for folks in the audience. I’m at Life Bio. Valter knows that. But, not everyone does. Could you just talk a little bit about what partial epigenetic reprograming is and why it’s the hottest thing in longevity science?
Longo
Yes, the hottest thing. I think there’s entire companies now based on that, I think Altos to a large extent is based on that. The idea is can you take lots of cells and, and make them from whatever age they’re at, can you reset the clock through four Yamanaka factors? Yamanaka Factors, these are factors that are when turned down together they make, normal cell and a pluripotent stem cell. Now that cell is young, but it’s also not what it used to be. Now you have a solution in a problem. And the solution is young. And the problem is like it might not know what to do. This is where you know, things like fasting come in and maybe guide the, the Yamanaka Factors in the right direction. Because fasting itself turns on Yamanaka Factors. But now the companies are forcefully, you know, pushing these in all kinds of systems. It’s working meaning like there are things certain tissues, for example, the Belmonte lab showed that skin wounds, are repaired more quickly with less fibrosis. But of course, again, now you’re turning on these factors in a very, uncoordinated way. That’s going to be the ultimate challenge. How do you coordinate that like it is in a beautiful way in a in, during embryonic development, where at each gene, each step is the result of 3 billion years of evolution. So now how do we how do we match these 3 billion years of evolution? That’s the ultimate immortality goal. So I don’t know that, that, that, you know, we’re anywhere near that. But certainly a lot of people are starting to think about that.
La Torre
Wonderful. Well, thank you so much for everything. You both are truly fueling longevity, and you are caring for the wellness of so many. Thank you for your research. Thank you for your leadership. Thank you for teaching and sharing with all of us.