What to Eat & When to Eat for Longevity: New Science | Lifespan with Dr. David Sinclair - S2, Ep. 3

25:02And it does that from amino acids and glycerol. That's the green line on the graph here, for those of you who are watching. Between 12 and 18 hours after your meal, fat burning ramps up even more. Now you're running mostly on free fatty acids, or FFAs. Ketosis begins around 16 hours, and for most people, it doesn't fully kick in till about 24 hours. That's also when autophagy starts to really switch on. That's the protein recycling. Ketosis is when your body produces ketone bodies for fuel. These are molecules like acetone. They tend to give you a bit of bad breath, but your brain really loves to consume them.

25:42They're called ketone bodies because biochemists many decades ago isolated them as separate substances or bodies from urine in diabetic patients. Then from 18 to 24 hours, with all those ketones in your system, something fascinating happens. Your alertness actually rises. And I actually feel this when I take a shot of the ketones. Besides ketones, certain hormones rise like adrenaline and noradrenaline. Evolutionarily, this was probably the time you needed to be sharp and motivated to go find food. At this stage of fasting, from 18 to 24 hours, thanks to more fat breakdown and some more gluconeogenesis, your brain and body get steady energy.

26:22By 24 to 36 hours, your liver is now producing even more ketones. These aren't just fuel. They're actually signaling molecules that turn on antioxidant defenses, improve mitochondrial efficiency, and even protect neurons. This is why many people report the fasting high, which is sort of a calm clarity that they get. Also at this stage, catecholamines like adrenaline rise even further mobilizing your fat stores growth hormone surges as well preserving lean muscle repairing tissues and supporting fat burning many people even notice their skin looks healthier after a prolonged fast by 36 to 48 hours you're in even deeper ketosis autophagy is probably at its peak the body is now running almost entirely on ketones and fat After 48 hours, ketones now dominate over glucose in the blood, and the brain relies on them for its fuel, sparing muscle from being broken down.

27:18If you go three days, what turns on is what's called chaperone-mediated autophagy, the really deep cleansing of misfolded and damaged proteins. That's about the limit that I've ever done. Some people go even further. They can go for a whole week without eating. I've never done that, but I'm sure that that has other benefits as well, including the real deep cleanse and of course weight loss if that's what you're looking for. But now let's talk about the opposite, what happens when we don't ever give the body a break from food. And that's how most people these days live. With frequent meals, blood glucose stays high and the pancreas is constantly pumping out more and more insulin.

27:55Over years, cells stop responding to that hormone and we get insulin resistance. The pancreas shouts louder, pumping out even more insulin, leading to chronic hyperinsulinemia, which just means too much insulin, all the time in the blood. Left unchecked, this drives type 2 diabetes, weight gain, and for men, erectile dysfunction. This constant high insulin increases inflammation, it reduces fat burning, and suppresses autophagy. So instead of steady energy, you get crashes, brain fog, and cravings. This is the standard lifestyle of today, with those constant meals and snacks in between. That excess sugar and fat, they don't just collect around the waist.

28:37They get stored in the liver, your pancreas, muscles, and even the heart. That's ectopic fat, and that's the most dangerous type of fat. Constant grazing, three meals a day plus snacking, it also disrupts circadian rhythms. Your sleep suffers, and hormones become imbalanced. And that, in turn, makes insulin resistance even worse. Over time, the cycle just accelerates aging and makes you in later life susceptible to diseases, not just diabetes, but even heart disease and Alzheimer's. And that's why fasting done correctly is really important. It breaks the cycle. It restores autophagy. It improves insulin sensitivity, and it reactivates the body's built-in longevity systems.

29:20Okay, let's take a moment to bust some myths. Because like most things in health, fasting is nuanced, and it's easy for the science to get buried under the internet hype and misinterpretations. Okay, myth number one, fasting will make you lose muscle. I hear this all the time. It's a common fear and it sounds quite reasonable, but if you fast wisely, not only can you preserve muscle, you can actually improve your body composition. In fact, a 2025 meta-analysis of 15 studies showed that healthy adults who practice time-restricted eating and they exercised regularly, lost more fat than those who exercised alone and importantly they also preserved their fat-free muscle mass.

30:03The key here is to make sure you're getting enough high quality protein, whether that comes from animal or plant sources. The current recommendation is 1.2 to 2 grams of protein per kilogram of your body weight every day, of course depending on your age and activity levels. This is 0.5 to 0.9 grams per pound of body weight for those in the US. But more is not always better. Too little protein can contribute to muscle loss and frailty.

30:30Dr. David Sinclair:While too much protein, especially if you're eating very high amounts, like 2 to 3 grams per kilogram of body weight, can also have downsides, especially in the long run, like high risk of type 2 diabetes, and especially if that protein is from red or processed meat. branched-chain amino acids leucine isoleucine and valine which are found more in meat than plants they actually activate mTOR which we've talked a bit about before which is good in the short term for the body it helps you heal grow but in the long term the goal is actually to keep the activity of mTOR low so actually I prefer to eat plant protein much more than meat so let's talk a bit about this it's a common argument on social media there are the protein folks and the meat folks and the plant folks.

31:15They're often debating which is best. What do I do based on the science? Well personally I tend to work out first of all to maintain my muscle mass as best I can, though it is hard when I travel. I tend to focus on plants much more than animals. In fact I try to be as vegan as I possibly can and I try to stay closer to the lower end of the recommended range range of daily protein intake. And just to be clear it's a personal choice. It's not necessarily a recommendation and I'm not trying to be Mr. Universe of course and my profession definitely doesn't depend on having a lot of muscle. But I do things that really count.

31:52I take the stairs when I can. I have weights in my TV room and I also have a standing desk every day. With my doctor I monitor my amino intake and nutrients and my blood levels. Every few months I go and have that tested to ensure I'm not deficient in any of these. And one reason I do this is because of great work by my ex-student Dudley Lamming, who's now an associate professor. His studies in mice have shown that reducing certain amino acids, the branched chain ones, especially isoleucine, can greatly improve metabolic health and even extend the lifespan of those animals, even when total calorie intake is the same.

32:32And I know I'm not a mouse, but the fundamental biology is the same between those animals and us. So now, that doesn't mean we should all just slash our protein intake in the hopes of living longer. Humans are not mice, and as we age, muscle is very important for other things, like stability, independence, avoiding falls, fractures, and even maintaining hormone levels. But for now, the practical point is simple. If you're fasting, make sure that when you do eat, you get enough high-quality protein to preserve muscle, and of course, all of the nutrients that you need. And remember, to prevent muscle loss in general, you do need to move and lift things.

33:09There's no way around it. Strength training is the signal to your body to keep building muscle. We know from being in space or just sitting in a chair your muscles are just going to degrade. You need to counteract that. So get up off your chair and walk, move and if you can lift weights. Let's remember that muscle is a longevity tissue. Building skeletal muscle helps reduce fat mass, it improves glucose control and it supports insulin sensitivity. Another reason you want to preserve your muscle mass is because muscles secrete what are called myokines. These are little molecules, sometimes just little peptides, that move around your body and help keep other organs healthy.

33:50Dr. David Sinclair:One of the things that we've talked about in this episode is that longevity really comes down to daily habits. Things like when you eat, how often you eat, and how much you move. and the good news is that even small changes when you stick with them over time can have a big impact on your health and your lifespan which brings me to a wearable that I'm particularly fond of partly because of its scientific foundation at Harvard where I work but also the founder's own research and scientific rigor. I'm talking about the whoop band which is the one that I rarely take off my wrist. This wearable is a health and fitness coach that gives me insights into my sleep recovery, and my body's strain.

34:30Dr. David Sinclair:Researchers have studied how accurate the device is, and in a 2022 study, they compared six wearable devices, including Whoop, against clinical-grade ECGs and sleep recording devices. Whoop showed strong accuracy for heart rate and heart rate variability, two measurements that are really important. Wearing the Whoop over the last two months, I've seen dramatic improvements in my personal biomarkers. For example, my resting heart rate has gone down to 45 which is quite a low number for me and my heart rate variability which you want to be high has shot up to 90 putting me in the top few percent for my age.

35:06Dr. David Sinclair:If you want to get a free Whoop 5.0 smart band and a month off membership go to join.whoop.com slash lifespan or at checkout use the code lifespan. All right let's talk about myth number two that fasting destroys your sex drive and your reproductive hormones. Let's start with a mouse study that's fairly recent. And in fact, I posted about this on X back in May 2025. In a recent cell metabolism study, old mice on intermittent fasting had better libido. They were very horny in this study and they had more frequent reproduction. And this is probably because the fasting reduced brain tryptophan, which lowered their serotonin and released the break on the libido.

35:48And in men and women, what we see during intermittent fasting is that levels of testosterone, estrogen, SHBG, which is sex hormone binding globulin, and other sex hormones, they usually remain stable even after a year of intermittent fasting. And in women with PCOS, which is polycystic ovary syndrome, fasting can even improve hormone balance. So no, besides maybe giving you bad breath from all the ketones and reducing your alcohol consumption, fasting isn't going to ruin your sex life. So now myth number three, will I be hungry all the time? It's true, hunger and cravings are common in the first week or so of fasting with ghrelin rising which is your main hunger hormone.

36:32But it usually adapts, by week two or three the hunger spikes calm down and fasting becomes easier. I usually find in my second week I don't even think about food. All right, now we're up to myth number four. My brain will shut off without food. That's actually completely false. After the second week of fasting, you get really used to it. If you run out of glucose, your body makes ketones. And this is actually really good for your brain. In fact, many people find that they think more clearly when they're fasting. All right, the next one. Myth number five. Fasting spikes cortisol and that's dangerous.

37:08This is kind of true. cortisol can rise during fasting but it's actually temporary it's an adaptive rise much like exercise it's really hormesis what doesn't kill you makes you stronger it's a mild stress that makes the body stronger that's not the same as the chronic harmful type of cortisol rise that you see in people who are stressed or just work out too much so no the rise in cortisol is probably not a problem during intermittent fasting. Next one, myth number six, fasting ruins diet quality. That's also not true. Studies show that whether people eat in a four-hour window or a 10-hour window, their overall diet quality stays about the same, even after a year.

37:54Macronutrient balance, proteins, carbs, fats, they stay stable. The sugar, saturated fat, cholesterol, fiber, and sodium all stay steady. All right, now let's talk about myth number seven. This is a common question I get. Will fasting lead to eating disorders? This one sounds alarming, but the data don't support it. In healthy adults, intermittent fasting has actually been linked to less anxiety around body image and fewer food cravings and even reduced binge eating compared to people who don't fast. In fact, many report feeling more in control of their food, not less. So rather than fueling disordered eating, fasting, when practiced mindfully, actually might help build a healthier relationship with food.

38:44Alright, so we've covered the myths. But like any good story, there's a twist. So let's talk about things that aren't known or agreed upon. Let's start with intermittent fasting versus calorie restriction, which is better. In animals, intermittent fasting extends lifespan, in part by turning on cell defenses similar to calorie restriction. Unlike animals, in humans, we just don't have strong evidence that fasting is equal or superior to calorie restriction for most people. But that said, fasting does have some unique benefits for brain health, cancer therapy, and even sleep that calorie restriction doesn't seem to provide.

39:21Moving on to the next concern. There's a 2024 conference abstract that many people saw. It made headlines at the time. It followed about 20 ,000 people for 15 years. It reported that people eating within an eight-hour window, a short time window, actually had higher cardiovascular mortality compared to those eating over 12 or 16 hours. Time-restricted eating also didn't show any benefit for overall lifespan or mortality risk. Sounds like a death blow for intermittent fasting, right? But here's the problem. The study was observational. It relied on self-reported data, and it also didn't account for diet quality and could reflect reverse causation, and it didn't account for confounding factors like pre-existing illnesses or lifestyle differences.

40:10We know that people, when they answer questions, they always lie, or they at least don't remember correctly. So while the study raised questions, it certainly doesn't outweigh the decades of controlled studies showing that fasting does improve metabolic health and reduces disease risk in humans. So now that we've covered the science, let's get practical. I know many of you have been waiting for this part. I'm going to give you a step-by-step guide on how to safely implement CR or fasting.

40:38Dr. David Sinclair:But before we get into the nuts and bolts of all of it, I need to be clear. First of all, I'm not a medical doctor. I'm a PhD scientist. And this podcast is for educational purposes only. Nothing here should be taken as medical advice, a diagnosis of any condition, or a treatment. And always consult your doctor or physician before making any changes to your diet or your lifestyle or your medications. Well, with that disclaimer out of the way, let's talk about the ins and the outs of fasting and how you might try it. So are you a good candidate? Let's talk about that. So fasting and the more severe calorie restriction are very powerful tools, but of course they're not for everybody.

41:18Dr. David Sinclair:You're probably fine if you're generally healthy, aged between 25 and 70, have a stable weight, and can sleep well, get some exercise in, and manage stress pretty well. Bonus points if you've got social support. But there are red flags, what doctors call contraindications. It's a no-go unless your doctor says it's fine. If you're pregnant, you're breastfeeding, trying to conceive, under 18, underweight, or have a history of eating disorders. Just really be careful and always consult your doctor when doing something major like this. The second thing to consider, step two, is what type of calorie restriction or fasting is better for you and your lifestyle.

41:58Dr. David Sinclair:Calorie restriction is more severe. You're eating less. You're also eating more often, whereas fasting is skipping meals or even skipping whole days of eating. There's also fasting mimicking diets that you might want to consider. Choose what supports your lifestyle and your other good habits like sleep, exercise, and relationships. If you prefer flexibility, time-restricted eating could be easier for you, or maybe the 5-2 method, which is five days of eating normally and two days of eating low amounts of calories, perhaps one meal a day or even skipping all the meals. If you're interested in calorie restriction, the sweet spot might be about 10 % fewer calories than normal, or maybe even 25 % if you want to go even more extreme.

42:41Dr. David Sinclair:But definitely not starvation. I want to be clear. You do not want to enter a period where you've got not enough nutrition. That's not what this is about. It's all about adequate nutrition, just enough reduction to trigger the health benefits while still fueling your body with enough protein, fiber, nutrients, and hydration. All right, the next step, step three, get a health check. You need to know what the baseline level is. First of all, to know if you're healthy enough, but also to know if what you're doing is actually working. I'll talk more about the specifics next, but you want to get a baseline set of labs, your vitals, even your physical performance, and of course record things like sleep and stress.

43:23Dr. David Sinclair:If everything looks good, you want to go for it. So how do you do that? Let's talk about step four. You want to ease into it. Don't go monk mode on day one. You'll fail. You want to cut back slowly. Start with about 5 % fewer calories than normal. Then start to shorten your eating window. Gradually drink plenty of water, tea, coffee. These help with satiety. You want to note down your energy levels, how hungry you are, and if your sleep and your mood is affected. All right, let's talk about the things that actually make fasting or calorie restriction possible. Rule number one, food and drink quality matter.

44:01Dr. David Sinclair:This is why some studies of fasting and plant-based diets don't show huge effects because not everyone eats quality food. You can be vegan and still eat potato chips every night or french fries. That's not healthy vegan. That won't work. You want to go for high satiety foods. These are foods that reduce your hunger and satisfy you. Also go for nutrient-dense foods and whole, unprocessed foods. These are things that you'll want because you're not eating as much typically, certainly not as often. Things that your grandmother would recognize. Eat foods that keep you full, like nuts, almonds and walnuts are great, soups, oatmeal, yogurts, I choose vegan yogurts, boiled potatoes are great, pulses and legumes like chickpeas, beans and hummus.

44:45Dr. David Sinclair:I love baba ganoush too. Choose foods with volume and nutrients without piling on the calories. Think leafy greens. Those are great because they fill you up, but they also have a lot of vitamins as well. Make sure you maintain enough protein intake. It's important for maintaining muscle mass. You'll be exercising. You also want to support your metabolism, and they also help reduce cravings. Protein's the best way to prevent hunger. Use herbs and spices instead of heavy sauces. Turns out spicy food actually can help with metabolism and reduce consumption of food. If you're doing calorie restriction or CR, think like a strategist.

45:21Dr. David Sinclair:Learn how to read food labels. There are apps like FoodUKate, Open Food Facts, and others. The other thing you need to do is eat slowly. It takes 20 minutes for your brain to register fullness. What I like to do is I put my knife and fork down. I talk to people. I chew slowly. Makes a big difference to how much you eat. And often you don't end up finishing the meal. You feel full by the time you get through it. And whatever you do, don't eat while distracted. There's nothing worse than eating while watching TV or doing your emails or doom scrolling. These are appetite amplifiers. Personally, I try to leave about 30 % of meals on the plate and put it in the fridge for later or take it home from a restaurant.

46:04Dr. David Sinclair:I've also spent many a night watching TV while eating and I go to bed feeling full and that is the last thing you want to do. And if you're fasting, stay hydrated. I've mentioned this a few times, but it's so important. Make sure you drink a glass or two of water before meals. It helps you feel fuller and it slows down how quickly you eat. So now let's talk about what to avoid. You don't need to be militant, but watch the usual suspects. Alcohol, I've given up, especially cocktails and mocktails, full of sugar. Avoid any sugary drinks if you can. Generally, all processed drinks and foods are bad.

46:40Dr. David Sinclair:Other things to avoid, of course, deep fried foods, calorie bombs hidden in sauces, dressings, mayonnaise and dips. Even though they taste great, you really want to avoid those. And especially those, if you look on the label, and they contain a lot of high fructose corn syrup. Sometimes even a little bit of dressing can add more calories than the salad itself. So be careful. And finally, you need to surround yourself with social support. You'll have slip ups. Take breaks when needed. Manage stress. and if your partner isn't supportive, in fact sometimes it's worse, they encourage you to eat, talk to them, explain why this matters and why this support is so important to you.

47:19Dr. David Sinclair:And lastly, be realistic. Nobody eats perfectly all the time. You'll have slip-ups. They happen, that's normal. I call myself a struggling vegan because I also sometimes have french fries, sometimes I overeat, but that's okay. You want to break your fast gently. You want to monitor your health, especially if you're doing prolonged fasts. And don't fast if you get sick. You need to recover. So eat well during those times. So let's talk about how you actually know if your fasting or calorie restriction is actually working. Is it doing you any good? So that's where tracking comes in. So if you want to do this right and safely, get your baseline labs before you begin.

47:58Dr. David Sinclair:Emphasis on before you begin. Then we'll retest every few months, especially if you're making big changes. Even before you get your labs, you can start simply. I would start by weighing yourself first thing in the morning. And, you know, don't worry if you fluctuate daily. You really want to just track your weekly average. It's much more reliable than daily fluctuations. I step on an electronic scale that records my weight, actually, and even tells me my body fat. It's a withing scale, and I love it, and I use it all the time. One of the big themes in this episode is that calorie restriction and fasting can improve metabolic health and support healthier weight loss over time.

48:36Dr. David Sinclair:But one thing I always say is you cannot optimize what you don't measure. Many people only measure their total body weight, if anything, but this only tells a small part of the story. When losing weight, you don't know if you're losing fat or muscle or even where the fat is being lost from. For instance, let's talk about visceral fat, the evil fat that sits around your organs. It's associated with increased risk of cardiovascular disease, diabetes, and even death. So getting rid of visceral fat in particular, or at least minimizing it, can have a strong impact on your long-term health and longevity.

49:11Dr. David Sinclair:How do you measure visceral fat? Well, it turns out that Withings, one of Lifespan's partners, makes some of the coolest devices that you can measure yourself with. Watches, a blood pressure monitor, and advanced bathroom scales. I've actually been using Withings devices for over 13 years since they first came out with their Wi-Fi scales. The Withings body scan scale can help estimate muscle mass, fat mass and even visceral fat. So let me show you what my body looks like in 3D. My digital twin on the Withings app, here it is on the screen here, shows changes in lean mass, visceral fat and even bone mass.

49:50Dr. David Sinclair:What you can see on my arms is 11.3 % fat and 14 % on my torso and visceral fat is pretty low at 2.7. I'm happy with these numbers. You can also look at muscle. The Withings scale is also the only smart scale that comes with an FDA-cleared ECG, which is really important for monitoring your heart health. And I measure that every morning when I stand on it. So we at Lifespan, we're partnering with Withings in part because we really believe in their product, but also because we share a common commitment to preventative health and also supporting medical research and young students. Learn more about Withings or get a scale or one of their other really cool smart devices at withings.com slash lifespan or for a 10 % off discount, use the code lifespan.

50:38Dr. David Sinclair:The other thing you can do is measure your waist circumference and your waist to hip ratio if you're brave. Sometimes I just use my belt to tell, but it's much more accurate if you get a measuring tape. It turns out the waist to hip ratio is an excellent predictor of your metabolic risk. It's even better than your body mass index or BMI. Some people like to get what's called a DEXA scan, which stands for dual energy x-ray absorbed geometry. These are mild x-rays that look inside your body. Personally, I don't really like them. X-ray exposure should be minimal because they break your DNA. And my lab has shown that actually accelerates aging.

51:13Dr. David Sinclair:So what about blood tests? Let's go through them now. You can get these tests from your own doctor or online these days. By the way, these are all in the show notes, so you don't need to take notes. One of the most important things to measure in any blood test, and especially when you're fasting or calories restricted, is fasting glucose. This is how much blood sugar you have after an overnight fast. You also want to measure what's called HbA1c, which many of you will know is when glucose gets attached to your hemoglobin. That's a more long-term measure of your blood glucose levels. You want to just make sure that you're not too low on those things.

51:47Dr. David Sinclair:And of course, not too high either. Another thing you want to measure is your hemoglobin, also your red blood cells and your hematocrit. The reason is that it often was low in the calorie study. So definitely monitor that. And if it gets too low, discuss this with your doctor. Now, the third thing that you want to measure, third group of things, is your lipid profile. Generally, you'll see improvements in these with fasting and calorie restriction. So you want to know where you're starting from. So that'll include so-called good cholesterol, HDL, bad cholesterol, LDL, ApoB, Lp little a, and triglycerides, and probably more.

52:23Dr. David Sinclair:Just talk to your doctor about that. When you're fasting and you're on calorie restriction, you need to make sure that you're not deficient in vitamins and minerals. So the vitamins that are important would include the B vitamins and vitamin D, among others, and also minerals, especially iron, and also magnesium, zinc, calcium, and phosphorus. You also might want to measure your omega-3 index. Make sure you're getting enough omega-3s. If you're not eating fish or taking a supplement, you might be deficient. You want to measure your liver and kidney function. I typically measure inflammation markers as well just to see them come down with my fasting regime.

52:56Dr. David Sinclair:These include CRP, AL6, TNF-alpha. These are also good predictors of longevity. And also, it's really important to measure your hormones, especially if you're female. That includes IGF-1, which is a longevity hormone, you want to have low levels of that. T3, T4, these are the thyroid hormones. And for men, especially testosterone levels. Also consider taking a DNA methylation age test. You can get these online and they actually measure the chemical changes on your DNA and they estimate your biological age. And that way you can see if you're actually getting younger by doing this. Just a word about biological age tests.

53:31Dr. David Sinclair:I like them so much and they're also based partly on our research. The reason I like them is that they're really encouraging. If I see a consistent dip over a matter of years, I really know that what I'm doing is working. I recently chaired a session at a conference at Harvard on the biomarkers of aging. And while the clocks aren't perfect, they're certainly getting better all the time. You also may want to use or try a continuous glucose monitor or a CGM. You also may want to track ketones. These go up, of course, as you're fasting. and the more you get into ketosis, as it's called, the more you'll see those rise.

54:05Dr. David Sinclair:And that's actually a good indicator if you're doing well. Tracking your vital signs is also really valuable. Your resting heart rate is good, heart rate variability, respiratory rate, and your sleep. If you don't already use a wearable, like a wrist strap, a watch, or a ring, I highly recommend one. Okay, let's move into some common questions I get all the time about fasting. Is there anything I can eat during my fast? I get this question all the time. But here's how I think about it. If you want to be strict about it, you really shouldn't be eating. I try not to eat and drink a lot, but a tiny bit of food is fine.

54:39Dr. David Sinclair:So personally, I have a teaspoon of yogurt in the morning with my supplements, and I might eat some nuts during the day if I feel peckish. I don't regard this as a fasting break, and it sure doesn't increase my glucose levels, and it doesn't lower my ketone levels. So, you know, I'm hitting my goals, so I'm not really worried about that. So water, some black coffee, unsweetened tea, herbal infusions, these are all fine. Just don't overdo it, especially on an empty stomach or you risk reflux or even gut irritation. And for those longer fasts over a day, make sure you're keeping up your electrolytes.

55:12Dr. David Sinclair:You can get the salts that you add to your water or drink coconut water. Another question I get pretty often is what medications and supplements can I take on a fast? And how do I take them if I'm not even eating? Always take your medications as prescribed. and if they need to be taken with food, you can still do that within a fasting framework. And while most supplements are fine while fasting, skip those protein shakes and especially those branched chain amino acid supplements. And as I said earlier, I often take my supplements, especially the fat soluble ones with a spoonful of yogurt in the morning.

55:44Dr. David Sinclair:So another question I get is, how often should I eat? Well, actually the science says there's a whole variety of things that can work depends on you. For most people, especially beginners, eating two solid meals works best. I prefer to eat one meal a day if I can. That works well for me. But in the beginning, it's a little tough. Over the first few weeks, you'll feel a bit hungry. And that's why two meals is a good start. When you start fasting, you'll find that it helps with your circadian biology. So you might even sleep better. It'll stabilize your energy and it'll even improve your metabolic health.

56:18Dr. David Sinclair:Focus though on quality food consumed twice or once a day. And then naturally people ask, should I skip breakfast? Is it important to eat in the morning? Well, it depends. Some scientific studies show that early eating aligns with better metabolism. Your body handles food better early in the day. And many people, especially women, around their menstrual cycle, they feel better eating before a morning workout. But if you're not hungry in the morning like me, don't force it. Most people's hunger hormone, ghrelin, is at its lowest around 8am anyway. I often skip breakfast, and it helps me fast longer.

56:55Dr. David Sinclair:Just don't let skipping breakfast turn into binging late at night. I often do that, and I regret it the next day. Make sure you still hit your protein and fiber targets too. Another question I get really often is, can I just work off the calories? Is that enough? Well, I still get the benefit. Well, exercise is similar in how it affects the body compared to calorie restriction. First of all, both of them signal scarcity. They put the body in adversity mode, forcing the body to become more efficient and more youthful at the cellular level. But there are big differences. Exercise is not the same as fasting or calorie restriction.

57:33Dr. David Sinclair:First of all, in multiple species, from yeast to worms, from flies to mice, and even monkeys, calories, calorie restriction extends lifespan up to 50%, but exercise alone only improves healthspan and delays disease. It doesn't significantly extend maximum lifespan in most models. Second, calorie restriction maintains longevity mode continuously, whereas exercise only triggers it intermittently. Thirdly, exercise primarily acts on certain tissues and organs like muscle, liver, and the cardiovascular system. These organs are directly engaged in movement and energy metabolism. In contrast, calorie restriction affects every tissue by persistently lowering anabolic signals and circulating growth factors.

58:18Dr. David Sinclair:Fourthly, calorie restriction uniquely activates aspects of DNA repair, epigenetics, and stem cell function. Exercise induces some of these changes, but not to the same magnitude or duration, especially in non-muscle tissues. So the answer is no, you cannot outrun a bad diet. All right, next question. Will calorie restriction or fasting hurt my exercise performance or gains? I hear this all the time. So let's start with the science. In the calorie study, people who restricted calories for two years without any structured exercise, they didn't lose any aerobic capacity. In fact, their VO2 max adjusted for body weight improved.

58:58Dr. David Sinclair:Their muscle quality went up too, even though absolute strength and lean muscle dropped a little. And a 2019 study of women who who had been resistance training, showed very similar results. An eight-hour eating window still supported muscle growth and performance. And a 12-week-long study of untrained people found that resistance training – oh, Andrew's brought it up on the screen – after a 10-12-hour fast overnight didn't impair their muscle growth or performance at all. But there are some caveats. In older adults, calorie restriction can sap muscle strength and reduce energy for peak performance.

59:31Dr. David Sinclair:So if your grandpa wants to win the Olympics, don't calorie restrict. And a 2025 study led by Andrew Galpin looked at 17 well-trained adults over eight weeks of resistance training four times a week. One group followed a 16-8 time-restricted eating pattern while training fasted in the morning, and the control group ate in a normal spread-out pattern. Both groups built upper and lower body strength and improved their muscular endurance, and both gained similar amounts of fat-free mass. But squat strength gains were slightly smaller in the time-restricted eating group, and they're reported feeling a bit less energized overall.

1:00:10Dr. David Sinclair:So the bottom line is this. Fasting or calorie restriction don't automatically ruin your performance. If you're well hydrated and eating enough protein, you can maintain muscle and strength. The best approach is to monitor how you feel when exercising, fed, or fasted, and track your performance and adjust. Now women often ask me, is fasting the same for us as it is for men? The short answer is no. Women's hormone levels can vary during the month unless the postmenopausal. Okay, let's pull up a graph of this. As you can see, in the first half of the menstrual cycle, when estrogen is higher, many women find they can tolerate longer fasts really well.

1:00:50Dr. David Sinclair:But in the second half of the menstrual cycle, during the luteal phase, when progesterone dominates, cravings, fatigue, and stress often increase, so longer fasts can feel even harder. So you might want to time your fasts for the first half of the menstrual cycle and go easier in the second half. Also, if you're trying to conceive, or if you're pregnant, or even breastfeeding, it's especially important to check in with your doctor before changing your diet. Another common question I get is, I've hit a plateau, now what should I do? We've all been there. Weight stalls, progress slows. So here's how I troubleshoot.

1:01:26Dr. David Sinclair:First, I tighten my eating window. Even an extra hour or two of fasting can make a big difference. Second, I adjust my training with progressive overload, lifting a little bit heavier than usual. I also try moving more, or using my standing desk more often. Even just taking meetings while walking is a great thing to do. So thirdly, I check my food quality. Sometimes I find that bad food has crept into my diet. So ask yourself, am I still getting enough fiber, protein, and water? Fourthly, I check my blood work. If things are really not changing, maybe I'm low on vitamin D, maybe my hormones are out, or I'm deficient in iron.

1:02:05Dr. David Sinclair:Many things can mess with your metabolism. And finally, I check my sleep and stress. Both can block progress, even if everything else is right. So remember, plateaus aren't failure, they're just feedback. So use them to recalibrate. And sometimes people ask me, well, David, isn't this really expensive with your monitors and supplements and scales? Well, that's true. You don't have to use all those things. If you're eating less, you're actually saving money on food. At the end of the day, your health span is always cheaper than disease. And fasting in its simplest form is actually free. So naturally, people wonder, won't calorie restriction or fasting affect my family or my social life?

1:02:47Dr. David Sinclair:And that's fair to ask. I thought that might happen too, but actually, cutting back on calories at a restaurant, not finishing a meal, taking a bit home, it's no big deal. And when it comes to drinking, cutting back on alcohol, initially my friend said, come on David, you got to drink, but if I just choose non-alcoholic beverages, they're totally fine with it. And with calorie restriction, it's often just about eating smaller portions, not skipping meals entirely. So don't be rigid. The goal isn't to emotionally starve yourself. It's to make this work with your life, not against it. And the last question for this episode, and one that I love is, can calorie restriction or fasting help my pet?

1:03:25Dr. David Sinclair:The answer is yes. Just like us, pets benefit from eating a little less. In fact, scientists at Nestle in the 2000s showed that Labrador retrievers on 25 % calorie restriction diets lived much longer. They got arthritis later as well, and they died from cancer much later than those fed normally. So if you're a pet owner, consider feeding your pet a little less often, but of course first talk to your vet to make sure it's okay. All of this is a powerful reminder that biology respects moderation. You want to put you or your pet into survival mode, and the way to do that is to not always be fed. It's true not just in us, but across species.

1:04:05Dr. David Sinclair:So what does the future look like? Well, right now we've got continuous glucose monitors, ketone breath sensors, and even AI powered meal timers. And these are just the beginning. Soon we might be using digital twins for personalized predictive medicine. A digital twin is essentially a virtual version of you, built from your medical history, blood tests, genetics, lifestyle, even your gut microbiome. And one day, these twins will hopefully be able to predict disease and test hypothetical lifestyle changes and design personalized health plans. Imagine going to sleep and waking up to a message from your digital twin.

1:04:44Dr. David Sinclair:Here's your optimal menu for today. Here's when you should eat. Imagine ordering takeout from an app that already knows all your needs. that future is closer than we think. We could also see designer gut bacteria, microbes engineered to release satiety hormones or short-chain fatty acids on demand, sort of like an internal fasting switch built right into your microbiome. Add to that even better epigenetic clocks and devices that can read your health a thousand times a second and predict diseases decades ahead. All of these and more could allow doctors or your AI nutritionist to recommend a fasting or a CR plan that is exactly what you need.

1:05:23Dr. David Sinclair:So we've now walked through the science of CR and fasting. We've talked about how to implement them safely and how to track your progress and even where this field is headed. But always remember, listen to your body and celebrate the wins. More energy, better sleep, cleaner skin, looser clothes. In future episodes, we'll dig deeper into supplements, sleep, wearables, and some of the big debates, including protein intake, red meat, and medications that might mimic CR, just like the GLP-1 weight loss drugs. I'll unpack the science, set the record straight, and help you make sense of it all. Stay tuned.

1:06:03Dr. David Sinclair:It's been great to have you with us. This is a show where science and evidence come first. The team works hundreds of hours to bring you only the facts. To learn more and to join our community, visit Lifespan.com and you'll get early access to future episodes, to the Lifespan magazine, and to detailed episode show notes. You'll also get transcripts and links to the papers that we talked about today. As a member, you'll actually be helping us support medical research to extend all of our healthy lives. If you found this episode valuable, do consider subscribing and also turn on your notifications so you don't miss new episodes.

1:06:41Dr. David Sinclair:It'll also help us make a better show for you. And feel free to share this episode with any family or friends who you think might enjoy it and learn from it. Finally, for the latest discoveries in longevity science, consider following us on Instagram at Lifespan and on X at Join Lifespan. From all of us at Lifespan, thank you for being part of this growing community. And remember, life's short, so let's change that together. Lifespan is produced by Andrew the Wonder Man Ying, Rajiv Geek Me Out Ramesh Marissa Who's On First Volgamore Kathleen TLDR Fitzgerald and our researchers Shivani Just One More Thing Sethi and Adiv Meet Me In The Year 3000 Johnson Also I want to mention our new recruit Daniel Rocketman Salazar who's our new producer and of course Serena My Honeypun I also want to thank Inspiro Studio and Create Ape for making this show possible and finally thanks to our partners for helping us support longevity research.

1:07:42Dr. David Sinclair:We'll see you next time.

1:07:53Dr. David Sinclair:This show is for informational purposes only and is not medical advice. Please consult a qualified healthcare provider as individual results may vary. Views expressed are my own and not those of Harvard University or Harvard Medical School. Full disclaimer is in the show notes.