Exploring Diet, Genes, and Aging for Longevity and Health

Nutrition 0:53 0
“So maybe we could start a little bit with what are you eating, then, to try to delay the aging process like what is...so diet obviously plays a very important role in aging and I'm trying to figure out exactly the best diet to eat and talk a little bit about what I think, but I'd love to get some of your thoughts.”

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Nutrition 1:19 0
“So I mean think the short answer is we don't know definitively, and I don't think we're going to know definitively if you define 'definitively' as a randomized clinical trial of longevity in humans.”

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Nutrition 2:24 0
“Then what we do in humans is we kind of rely on our best proxy biomarkers that we think reflect the systems that drive aging and we can measure those things over time and sort of estimate what we think is the effective this dietary change or that dietary change or this lifestyle change or that drug change on those things.”

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Nutrition 6:27 0
“I mean that's, sort of, my biggest obsession, I think, is probably around those topics. So it's complicated. I think we have probably a better understanding of mTOR. I mean I think it's very clear that mTOR is amino acid driven.”

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Substances 7:02 0
“Why do bodybuilders or people who love lifting weights, want to take Branched-Chain Amino Acids while they're exercising? The reason is largely through this empirical observation that it enhances muscles growth and/or prevents muscle degradation during exercise.”

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Substances 7:29 0
“It's pretty much all leucine. And what's really clever just from an evolutionary perspective is that mTORC in muscle has a much higher affinity for leucine than mTORC1 in fat or in hepatocytes.”

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Substances 8:31 0
“5 grams of leucine during a workout, probably not harmful.”

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Substances 9:19 0
“One camp says IGF-1 is driven exclusively by amino acids. The other camp says, no, it's actually driven by amino acids and carbohydrates.”

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Nutrition 17:11 0
“The conceptual way to do it, at least the way I do it, is you consume more or less the least amount of protein you can consume to maintain and grow muscle mass. But you don't need any more than that.”

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Nutrition 17:43 0
“Carbohydrate, we are basically lowering it until we reach the highest point...or pardon me, the lowest point that we can tolerate where we can maintain, and again, this is the lowest possible fasting insulin.”

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Nutrition 19:19 0
“And then basically, fat becomes the fill. And so the point here is that that becomes a highly different diet for different people. For some people that's 40% carbohydrate and 20% protein, and the remainder of fat.”

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Gut health 20:12 0
“I mean that's you've got more immune cells in your gut than you do in any other organ of your body and your gut bacteria, the interaction between your gut bacteria and your gut are also, you know regulating the types of immune cells that you're making, regulatory T cells being put in that.”

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Gut health 20:39 0
“So eating things that are good for your gut like fiber and avoiding things that are going to cause a lot of gut damage.”

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Nutrition 20:53 0
“Micronutrients are cofactors for a variety of enzymes and proteins in the body. It makes sure they're functioning proteins that are involved in these processes we're talking about, keeping cancer cells in check.”

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Gut health 23:16 0
“So I started working with her. It became pretty clear to me that there was something in her diet that was creating an inflammatory environment that wasn't a structural problem.”

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Gut health 26:25 0
“I've become more convinced that the endotoxin released from the gut which is a constant...I mean, really the major source of inflammation in the body is coming from the...”

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Gut health 27:32 0
“There is some interesting work coming out of, like, Justin and Erica Sonnenburg Lab over at Stanford. I recently had a discussion with them on looking at the role of fiber and certain types of fiber in fueling different species of bacteria in the gut and how those are generating short-chain fatty acids and other signaling molecules which are regulating hematopoiesis, they're regulating the number of Tregs that we're making.”

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Nutrition 27:57 0
“So it is very interesting that feeding our gut certain types of fiber which are present in vegetables and a variety of fruits even, do have a positive effect on the immune system via the signaling molecules that are being made in the gut.”

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Genetics 30:07 0
“I've actually got one ApoE4 allele, so I'm very interested in ApoE and I'm actually writing a paper on ApoE4 and its role in Alzheimer's right now.”

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Genetics 32:01 0
“So when they measured the serum level of ApoE it turned out to be more predictive of Alzheimer's disease than the genotype.”

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Genetics 33:01 0
“I'd be happy to show you the paper because that's... Yeah, that's interesting because from my understanding, you make ApoE in the liver and you make it in the astrocytes.”

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Genetics 34:12 0
“The 4/4 was really viewed as, 'Boy, you're guaranteed to have an MI before 60.' And I think the evidence today suggests that once you normalize and correct for LDL particle number or ApoB, it stops mattering.”

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Genetics 35:28 0
“Between 65% and 80% of all the Alzheimer's cases, so... The majority even have at least one allele. Yeah. 3/4s.”

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Nutrition 37:04 0
“Looking at epidemiology, you see certain lifestyle factors for example, drinking. If you're drinking in your ApoE4 because you're inducing damage that you can't repair as well, you're going to fare worse.”

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Disease prevention 39:49 0
“And we definitely know that diet and lifestyle play a major role in your risk for cardiovascular disease.”

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Disease prevention 40:38 0
“The three things that have, I think, allowed cardiac disease to remain...in fact, it's actually come down. If you look at the death rate from cardiac disease, it's come down.”

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Disease prevention 41:00 0
“The data are really clear that if you could only make one behavioral change to reduce your risk of heart disease, it's don't smoke.”

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Disease prevention 41:47 0
“Think of the litany of drugs we have for controlling hypertension and think about the litany of drugs we have to bring down ApoB.”

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Disease prevention 42:27 0
“We know that in the last 50 years, the prevalence of Alzheimer's disease has gone up about 2.5%...per year, by the way.”

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Disease prevention 44:06 0
“I sort of view Alzheimer's disease as brain diabetes, and I think if the ApoE genotype as basically just a susceptibility.”

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Metabolic health 46:04 0
“I firmly believe that if you can be as insulin-sensitive as possible, for you as an individual you reduce your risk.”

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Disease prevention 46:24 0
“I know that if I have to choose between being very-insulin-sensitive and not-so-insulin-sensitive I'm going to be better off in this camp.”

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Substances 46:44 0
“Amgen had a drug that was an IGF-receptor antibody. It went into clinical trials, phase two trials in pancreatic cancer, advanced pancreatic cancer, and it failed.”

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Nutrition 47:30 0
“There is ongoing research, it's all in animals at this point in time, that's looking at giving a diet that actually increases IGF but giving it in the presence of this IGF-receptor antibody.”

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Disease prevention 53:29 0
“people with TBI are much more likely to get Alzheimer's especially if they have ApoE4. You know, up to 10 times, 20 times, depending on how many alleles they have, but...”

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Disease prevention 53:50 0
“I would advise somebody who's an ApoE 3/4 entering the NFL that your number of concussions should be fewer than what is recommended.”

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Disease prevention 54:31 0
“George Brooks, a friend of mine, he's working now with some other physicians at UCLA looking at the effects of actually exogenous lactate on helping treat TBI.”

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Disease prevention 55:13 0
“They're both thermodynamically favorable, they allow glucose sparing, they allow glucose to then be used to make glutathione, which is important in the brain when you have damage.”

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Disease prevention 59:23 0
“Cancer cells are primed to die in the sense that our body has increased the amount of all these pro-death signals, pro-apoptotic proteins to say, 'Die, die, die.'”

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Disease prevention 1:00:03 0
“And I think that is one of the main reasons why giving DCA, activating the pyruvate dehydrogenase complex, can kill cancer cells.”

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Nutrition 1:00:16 0
“I think that's why ketogenic diets, which are basically forcing the cell to use oxidized fats which require a mitochondria, I think that's also why they're very effective at...”

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Disease prevention 1:01:53 0
“It's also why taking supplemental dietary antioxidants when you have cancer is very dangerous because you're blunting that whole signaling pathway, right?”

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Most important takeaways of the video

  1. Diet is crucial in delaying the aging process, but the best diet for aging is still a topic of exploration and discussion.
  2. Definitive answers on the best diet for longevity are unlikely due to the impracticality of conducting long-term randomized clinical trials in humans.
  3. In human studies, researchers use proxy biomarkers to estimate the effects of dietary and lifestyle changes on aging, helping infer potential longevity benefits.
  4. Leucine is the most significant among Branched-Chain Amino Acids for muscle growth, with mTORC in muscle having a higher affinity for leucine.
  5. Consuming fiber-rich foods is beneficial for gut health, while avoiding harmful substances can prevent gut damage.

Introduction to Aging and Nutrition

Diet is a pivotal factor in the aging process, yet defining the best dietary strategy to delay aging remains uncertain. Conversations suggest that understanding which diet effectively slows aging requires broad discussion and ongoing research.

The Role of Clinical Trials and Biomarkers

The complex nature of aging makes definitive studies through randomized clinical trials infeasible. Instead, researchers rely on proxy biomarkers to estimate the impact of dietary changes on aging and longevity.

Understanding mTOR in Aging

The mechanism of mTOR, particularly how it is activated by amino acids, is a significant focus in aging research. Branched-Chain Amino Acids (BCAAs), like leucine, are noted for their role in muscle growth during exercise, suggesting their importance beyond just muscle-building to general aging.

Optimizing Macronutrient Intake

Strategies discussed for longevity involve moderating protein and carbohydrate intake to minimal levels necessary for maintaining health, while adjusting fat consumption to meet individual dietary needs.

Importance of Gut Health

The gut plays a crucial role in overall health by harboring extensive immune cells and interacting with gut bacteria to regulate immune functions. Dietary fibers support this by fostering beneficial gut bacteria that produce health-promoting short-chain fatty acids.

The Role of Genes in Aging and Disease

Discussions on genetics centered around the ApoE genotype, highlighting its association with Alzheimer’s disease. Differences in how ApoE influences cholesterol handling and repair mechanisms in the brain suggest that lifestyle adjustments, like reducing alcohol intake, can be particularly beneficial for individuals with specific ApoE genotypes.

Prevention and Management of Diseases

Preventive strategies for diseases such as Alzheimer’s and cardiovascular diseases emphasize the importance of lifestyle choices, particularly smoking cessation, insulin sensitivity, and dietary precautions. The interplay between diet, lifestyle changes, and pharmacological interventions continues to be a prime focus in reducing disease risk and managing health.

Current Research and Future Directions

Emerging research includes exploring the effects of diets on IGF levels and treatments like exogenous lactate for conditions like Traumatic Brain Injury (TBI). These studies highlight the evolving understanding of diet and nutrient management in disease prevention and aging.