David Sinclair Podcast 2: “What to Eat and When to Eat for Longevity”

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by Nils Osmar. January 12, 2022

This article has some show notes and a commentary on David Sinclair’s new podcast (and a link to the video).. Some of his key points this time:

  • Eat less often.
  • Don’t snack.
  • Restricting calories “works”
  • Taking pills isn’t sufficient. We need to start with the diet, then add the pills
  • This diet saves money on food, which may help people who struggle with the cost of supplements.
  • Eating less glucose (when feeding yeast) increases their lifespan. The same is true of humans and other organisms. Stevia and other naturally occurring zero calorie sweeteners are fine.
  • Sirtuin genes get triggered by low energy. (They can also be activated by low heat; high heat; certain amino acids; high salt). The role of sirtuins is to extend the lifespan. “Low energy activates PMC1 gene in yeast, which activates the sirtuins because the gene makes more NAD, which the sirtuins use as fuel.”
  • We can mimic low glucose by giving them NAD boosters (NMN or NR).
  • mTOR is activated if we eat a lot of protein. “But this is not a recipe for longevity.” When we’re hungry, autophagy kicks in and recycles old protein fragments.
  • “When you’re hungry, you’ll make more AMPK and make more mitochondria, and you’ll also fight aging.”
  • This has been proven in animals but it may be decades till it’s fully proven in humans. The research comes (so far) from model organisms, not humans.
  • Placebo-controlled, double blind studies are now being conducted in humans. But they’ll take a while to complete. Some people are not waiting; they’re going ahead and applying this information, changing their diets or taking rapamycin or metformin, which gives us some anecdotal evidence. “Anecodotal evidence guides the clinical trials.”
  • People who are obese are more likely to age faster, die younger, and have a variety of health problems. But if they fast (whether or not they lose weight) they can get the same anti-aging benefits as people who are lean. He notes that we don’t fine “giant men who are obese” in nursing homes, but “little women who are skinny”, suggesting that being skinny promotes longevity. I’m not sure though that anyone would want the life those women have.
  • Fasting also has a protective effect against cancer and heart disease.
  • Sinclair also talks about “How should people fast?” His answer: It depends on the individual. We come in different genders and different ages and have different microbiomes. There’s no “one size fits all” when it comes to fasting. He recommends trying different diets and fasting regimens and testing with a __ like Inside Tracker.
  • Sinclair has been skipping breakfast since he was a teenager (though he does take a couple of spoons of yogurt in the morning to make sure his supplements are absorbed).
  • When you do this for a few weeks, your liver will start generating glucose from your liver (gluconeogensis).
  • It’s essential (in his opinion) to avoid eating carbs in the morning which raise your blood glucose and insulin, then leave you feeling like you’re starving. Just skip breakfast instead.
  • Sinclair is not a purist about fasting. It was difficult for him to fast all day till he learned that (for him) filling his body with fluids such as coffee or tea. If he still feels really hungry and feels an urgent need to eat some food, he’ll eat a handful of nuts. “The protein will stop your hunger.” He also drinks a green drink (Athletic Greens) in the morning so as to provide some nutrition to hold him till dinner.
  • We don’t want “the hangries”… mice get angry during a fast and attack each other.
  • He’s a strong advocate of “mostly vegetarian” diets such as Mediterranean diets (plus exercise), which include some fish but comes mostly from plants. He’s also a big fan of the Okinawan diet, though it contains a lot of rice, which does not recommend. “The Okinawans are arguably the longest lived people in the world.”
  • It’s not all about food; exercise and social structure are associated with long lives.
  • “Programming the epigenome for health requires some hunger.” Encouraging children go constantly eat and snack is not setting them up for a lifetime of health and longevity.

Approaches to Fasting

He mentions several approaches to fasting, all of which lower mTOR and activate AMPK. They include

  1. The Prolon Fasting Mimicking Diet advocated by Dr. Valter Longo
  2. Prolonged fasting (3-5 days)
  3. Time restricted feeding (such as trying to not eat till dinner) (At least 16 hours of fasting a day) (16/8).
  4. There are deeper benefits to shorter time frames for eating, such as 20/4).
  5. “Try no breakfast or lunch for two weeks.” It should get easier (your hunger should go away) by the end of the two weeks, as your body adapts.

What Should We Eat (and Avoid)?

  • We should not be eating sugar (glucose or fructose) they’ll get fatty liver disease. Plus, sugar switches off sirtuin genes. Glucose attaching to protein will give increase AGEs. So no fruit juice or sugar in the morning
  • Don’t eat “a big bowl of ice cream every night” (but it’s okay to have a few bites)
  • Avoid super-high protein. Very high levels of protein switch off the sirtuin genes. “mTOR can be activated, but you don’t want it activated all of the time.”
  • “If you’re an athlete or want to. bulk up, you’ll feel better if you eat meat. But (carnivore diets) are not beneficial to longevity.”
  • He’s not a vegan, but is “trying out” a vegetarian diet (which does include some fish and some yogurt in the mornings.) He loves meat and thinks it tastes great. But he’s avoiding it “for now.”
  • High amounts of amino acids such as leucine and isoleucine will switch on mTOR.
  • “If you want to eat meat, go for it. But try to focus on plant-based foods more often (at least part of the week), so there are periods in the week when your leucine and isoleucine aren’t floating around in your bloodstream.”
  • There may be benefits to eating plants that have experienced stress. He looks for plants that are organic, local and colorful. Bright colors indicate that they have survived stress and may be high in compounds that help activate the sirtuin genes.
  • He acknowledges that if we are actively building muscle, we do need more protein, and more leucine and isoleucine. But, again, he encourages people to still take some breaks from protein to turn on autophagy and activate AMPK.


My Thoughts:

  • I love listening to Sinclair and have learned a lot from him. I really like his podcast.
  • The science seems very clear that there are benefits to activating AMPK. But there can also be benefits to activating mTOR periodically to build muscle. So I was glad to hear him acknowledge that in this podcast.
  • In my experience (at least at my age), if we only activate AMPK, we’ll start wasting away. James Clement has written about the importance of doing both, and the dangers of overactivating AMPK and underactivating mTOR. 
  • In this video, Sinclair emphasizes that if you do choose to eat a lot of meat, it’s good to take breaks from doing so frequently. For this reason, he’s not a fan of carnivore diets. (I’d like to hear him at some point address the approach of people like Paul Saladino, who eat nose to tail (not just red meat) and take long breaks in the form of fasting; like Sinclair, Saladino gravitates toward eating one meal a day.)
  • He advocates “reducing the amount of red meat and in particular processed meat.” He mentions that TMAO promotes cancer and cardiovascular disease. However (this is a bit of a contradiction to me), he does eat fish, which is high in TMAO. “Eating meat is not going to kill you, but try to push yourself toward eating more plant based.”

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