Nutrition, Exercise, Genetics, and Longevity: Key Points for Health

Nutrition 0:28 0
“I don't think a week goes by that we aren't exchanging an email about some aspect of the relationship or the interspace between nutrition and longevity.”

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Nutrition 0:56 0
“I think the biology of nutrition is equally complicated and you know when you get at the interface of those two, it's really hard I think sometimes to draw a definitive conclusion.”

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Environment 3:00 0
“The big piece that gets lost with the animal models on top of all that complexity is the environment.”

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Nutrition 6:12 0
“are you over nourished or undernourished”

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Body weight 6:16 0
“are you under-muscled or adequately muscled”

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Metabolic health 6:24 0
“are you metabolically healthy or not”

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Nutrition 7:18 0
“what's your protein intake need to be to achieve that in combination with your calorie needs”

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Nutrition 11:02 0
“if you can be you know somewhere close to optimal nutritional intake right just say total calories regardless of composition, body composition is somewhere close to where it should be, that's a big chunk of what you need to give yourself the best chance of being healthy going forward.”

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Nutrition 12:38 0
“you can just get 80 of this right by focusing on exactly what we've talked about and the details the complete optimization are not worth it.”

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Exercise 12:55 0
“it's instead better to put that effort into exercise that's where i think if you're going to really go down the rabbit hole and put more of your mental energy more of your time and more of your focus into something you have far more of an roi on the exercise front than eking out incremental value on the nutrition front.”

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Nutrition 14:49 0
“caloric restriction seems to reproducibly improve lifespan.”

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Nutrition 16:53 0
“if you restrict nutrients by a whole variety of different methods, you can increase lifespan and apparently increase health span proportionally.”

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Nutrition 17:30 0
“caloric restriction can slow aging in laboratory animals pretty much everywhere where it's been studied.”

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Nutrition 20:16 0
“could it be the case that really what caloric restriction is doing is preventing cancer and that's why you see these big increases in lifespan?”

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Nutrition 20:59 0
“caloric restriction seems to delay, prevent those declines as well.”

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Genetics 22:45 0
“you could use an epigenetic clock for that reason um you know in in in my world as part of the dog aging project there are many dogs you know that are rescued an owner might want to know their age so i think that is a that is a real use and clearly the clocks will work for that”

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Genetics 22:58 0
“i think really what you're asking though is can i convince you that the epigenetic clocks and potentially other types of clocks are actually measuring biological aging correct and that's a harder in my mind that's a harder thing to prove and personally i have no interest in convincing you of that because i'm not convinced”

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Genetics 24:06 0
“what they've done comes close i guess so what has been done is to look at longitudinal studies in people where we have samples from people 10 20 30 years ago measured the epigenetic profiles of those people 10 20 30 years ago and ask how well does that correlate with mortality outcomes for example in the future”

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Genetics 25:58 0
“reversing the epigenome is reversing aging is at best an exaggeration at worst an outright lie i mean it's just not true”

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Genetics 28:14 0
“the experiment to do would be to express these reprogramming factors in an old mouse and make that mouse young again.”

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Genetics 29:06 0
“nobody has ever taken an old mouse and and turned it into a young mouse.”

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Genetics 31:42 0
“what these epigenetic changes the methyl groups that you were talking about do primarily we think is affect expression of the genes.”

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Genetics 34:13 0
“those are called mutations and those accumulate as we age and that's honestly what drives a lot of cancer right yeah so we've known this for a long time”

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Genetics 34:24 0
“the epigenetic changes are sort of on top of that right yeah and while it more regulates expression right”

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Inflammation 34:50 0
“inflammation is a huge driver of our loss of ability to recover as we get older”

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Genetics 36:03 0
“you will not fix mutations by fixing the epigenome”

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Genetics 38:22 0
“changing the epigenome which is the nuclear genome isn't going to fix anything that's wrong with your mitochondria directly but maybe by fixing the epigenome you restore the homeostatic mechanisms that then maintain mitochondria in a healthy state”

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Substances 39:13 0
“we see that short-term treatment with rapamycin in mice makes an old heart function functionally to some extent more like a young heart”

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Cognitive stimulation 40:03 0
“how do you ensure that you can reprogram somebody's brain in a way that isn't going to change that”

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Exercise 42:13 0
“nobody's sort of paying attention to what they eat or how much exercise they do because i don't need to this is going to be worked out”

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Exercise 47:55 0
“you get most of the benefit going from you get i would say literally 50 of the benefit based on at least the the so-so epidemiologic data about 50 of the full benefit of exercise is captured going from nothing to about 15 met hours per week”

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Exercise 48:46 0
“15 met hours per week is but by extension i do about a hundred met hours per week of exercise”

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Disease prevention 50:26 0
“people have done pathogen challenges on cr animals and they respond better at least the old animals respond better than than age-matched ad libitum fed control.”

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Disease prevention 50:45 0
“the sepsis experiments are pretty clear with the cr animals compared to controls when you induce sepsis in them the cr animals die much more quickly.”

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Nutrition 51:10 0
“optimal cr with optimal nutrition so you might sometimes you'll see this cron c-r-o-n right caloric restriction with optimal nutrition or cran caloric restriction with adequate nutrition.”

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Disease prevention 52:13 0
“you may affect some aspects of the biology of aging in a way that you're aging biologically more slowly that doesn't matter if you get influenza and die.”

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Body weight 55:28 0
“this depending on the change in lean body mass yeah this is just a complication of the cr studies”

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Body weight 56:45 0
“the exercise driven weight loss group did not experience a reduction in bmd but the cr group did”

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Body weight 57:20 0
“we know if you go on cr you're going to lose weight”

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Body weight 58:55 0
“what are the risks associated with significant caloric restriction in people as a therapeutic strategy”

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Body weight 1:00:46 0
“the cr animals the calorically restricted animals were fed 25 of what the control animals were fed”

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Nutrition 1:01:55 0
“the diets were different so that's maybe a good contrast these animals were actually fed the closest diet that could mimic their real diet um so it didn't have any you know sugar in it really i think it was like about three percent sucrose um you know it was almost kind of like a vegetarian pescetarian sort of diet uh fish was the dominant source of protein but it it was a high quality diet relative to the wisconsin air quality for sure”

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Metabolic health 1:06:03 0
“the question though in my mind is between these two studies do they suggest that caloric restriction you know slows aging and let's just start relative to the typical american diet right somebody is moderately obese and they're eating terrible is it caloric restriction or is it just returning to i think maybe what you would call like an optimal body weight right optimal uh uh body mass and i don't think we know the answer right i think from these studies you can't draw many conclusions”

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Nutrition 1:07:04 0
“if you see the same molecular changes it's suggestive that caloric restriction is having the same molecular changes in people certainly in primates and in fact that seems to be the case a lot of what we see in terms of you know changes in mTOR signaling and mitochondrial function and other metabolic pathways is in fact shared between mice and monkeys.”

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Nutrition 1:08:17 0
“what the wisconsin experiment suggests is if you have an awful diet reducing the amount of awful food you eat is a good thing.”

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Metabolic health 1:11:01 0
“you might argue that they're still getting metabolically sick right just as humans when you're over fed the real metabolic sickness comes not with the inflation of your subcutaneous fat it's when that spills out into the viscera into the liver into the peripancreatic space into the perinephric space into the pericardial space it's that fat that escapes the normal depot of sub-q fat that is truly inflammatory and truly metabolically disturbing.”

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Nutrition 1:12:51 0
“when you get 28 and a half percent of your calories from sugar, it's probably going to impair your metabolism.”

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Nutrition 1:13:59 0
“our evolution necessitated the most flexibility from a nutritional standpoint.”

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Nutrition 1:14:49 0
“people seem to be able to tolerate a wide variety of different diets some of which are pretty darn bad for them for many many years before you start to really see the significant consequences.”

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Nutrition 1:15:17 0
“you can look at somebody eating a really well formulated strict vegan diet where they're not getting any animal protein which clearly our ancestors all had animal protein whenever they could, they're often protein a little protein malnourished but they're very healthy.”

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Nutrition 1:18:39 0
“eating a carrot is inherently less risky than eating a protein bar with 14 ingredients in it.”

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Nutrition 1:19:46 0
“I've been thinking a lot about caloric restriction and particularly other nutritional strategies that people have been studying in the field like ketogenic diet, protein restriction, time restricted feeding, intermittent fasting.”

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Nutrition 1:24:24 0
“the experimental group ate less calories than the right so it's time restricted feeding but it's really caloric restriction in a narrower window”

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Circadian rhythm 1:25:25 0
“there's evidence that it's not only about how big the window is but where in the day the window is and that's actually one of the things that that you know came out of our our review of the literature is there is this clear connection between how much we eat and when we eat that ties into circadian rhythms”

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Nutrition 1:26:13 0
“fasting mimicking diets are diets that have been engineered to some extent to induce the same metabolic changes as caloric restriction usually very low sugar relatively low protein high fat but also very low calorie”

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Metabolic health 1:29:05 0
“a mouse will go into ketosis relatively quickly within 24 hours right and a human can go into ketosis that quickly depending on their incoming diet.”

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Metabolic health 1:30:47 0
“those mice are fed a calorically restricted diet they're also fed three times a week so they are in fact that's insane it's like they're they're basically doing a two-week fast between their meals.”

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Metabolic health 1:31:58 0
“two-thirds of the benefit came from the reduction in calories and a third of it came from the additional fast.”

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Metabolic health 1:34:50 0
“early feeding produces an overall lower average glucose for sure because even if you get the same spike, let's say with an early like if you're doing the same meal early in the day versus late in the day, there's something about how long it takes to come down.”

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Nutrition 1:36:20 0
“I'm very very hesitant to suggest that people should adopt any of these diets based on the rodent literature where it's at today.”

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Nutrition 1:37:58 0
“Intermittent ketogenic diets in mice can increase lifespan and seem to have benefits for health span.”

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Nutrition 1:38:18 0
“There are two nutritional interventions that relatively consistently give big effects on lifespan: one is caloric restriction and one is protein restriction.”

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Nutrition 1:40:36 0
“you know we should we should be realistic and recognize you're never going to get a significant fraction of the population to calorically restrict. It's hard enough to get people to calorically restrict down to a healthy weight, to get them to go 30% beyond that it's just not going to happen.”

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Nutrition 1:41:10 0
“true caloric restriction has real psychological consequences.”

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Nutrition 1:41:28 0
“there's social isolation that you get when you're calorically restricting but then there's the biological changes in the brain and you're hungry all the time.”

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Nutrition 1:42:52 0
“if you do a graded onset of caloric restriction in other words don't go right from ad-lib to 40% restriction the next day if you do sort of a graded onset you can get lifespan benefits from caloric restriction you know 20-22 months of age.”

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Nutrition 1:46:29 0
“so then the big question here is what happens if you start caloric restriction late in life or what this study did that i'm not really aware of anybody you know doing previously is kind of the flip it's almost like a crossover.”

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Nutrition 1:47:30 0
“those animals actually were longer lived than the mice that went on cr late in life.”

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Nutrition 1:49:09 0
“with rapamycin you know the data are pretty clear that you can start rapamycin certainly well into middle age and maybe even a very old age and get most of the benefit.”

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Substances 1:51:25 0
“he nominated rapamycin it got selected it went into the cohort and they typically test five or six interventions or drugs each year so they have a huge number of animals at each of these three sites that are destined for these interventions to be tested in and rapamycin was one of them.”

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Substances 1:52:36 0
“once they finally developed this in what they call e-wrap encapsulated rapamycin it it's basically designed so that it won't break down in the gastric ph once they developed that they were now 18 months into this lifespan experiment”

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Substances 1:54:32 0
“same thing seems to be true in people so you know there are people who are getting their rapamycin from uh from like the rap immune which is the brand name generic or the brand name sarah limus that likes comments comes in these triangle-shaped pills they're also people who are getting it from compounding pharmacies and i've heard of several cases now where the bioavailability is much lower in the the compounded rapamycin in a capsule”

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Nutrition 1:55:43 0
“as you said the protein restriction and i think of all the topics in nutrition this is the one i'm most interested in uh i really don't care that much about fat and carbs don't tell anybody but i care an awful lot about protein”

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Nutrition 1:56:28 0
“if you consume too much protein in one sitting uh and it's typically more than about 0.25 grams per pound is the general thinking you're going to end up oxidizing some of that protein so it's not that it's harmful it's just that you're not getting the amino acids you need for muscle protein synthesis which is of course our objective.”

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Nutrition 1:57:10 0
“the recommended daily allowance of protein is 0.8 grams per kilogram, which is less than half of what I would consume.”

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Nutrition 1:58:50 0
“you can extend lifespan through protein restriction and there are actually again a couple of flavors of protein restriction you can restrict all protein down to some percentage some low percentage um or you can restrict specific amino acids particularly branched chains tryptophan methionine or branched chain amino acids are the ones that have been studied.”

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Nutrition 2:02:34 0
“the branched chain amino acid and methionine restriction studies are pretty clear that those animals are consuming more calories more calories than certainly if you matched a weight then they add little mice and they're living longer.”

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Nutrition 2:04:09 0
“when you consume a protein-rich meal, do we have a sense of how long mtor is being activated in response to that set of amino acids?”

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Nutrition 2:04:42 0
“if you're going to pound branching amino acids during a workout because you want as much anabolic signal as possible, it's going to be very difficult so much so that the idea of using bcaa analogs to treat sarcopenia was going to require drugs that could stay on much longer.”

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Nutrition 1:28:44 0
“what the mice are eating and when they last ate has if anything as as big maybe bigger effect on mtor signaling than rapamycin”

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Nutrition 2:10:34 0
“most of the diets where the mice lived the longest were towards the low end in protein”

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Nutrition 2:11:00 0
“the diet that actually gave the absolute longest lifespan had like i don't know it's like a 40 protein in it”

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Nutrition 2:12:52 0
“our muscles are a sink for glucose they are the single most important sink we have for glucose and our ability to tolerate glucose and maintain glucose homeostasis in the presence of larger more metabolically healthy muscles is the difference between having diabetes and not having diabetes”

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Exercise 2:13:56 0
“just monitor the activity level of people over the once they hit 75 they fall off a cliff so muscle mass dramatically plummets activity levels dramatically plummet”

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Nutrition 2:14:46 0
“how important is dietary protein in that maintenance of muscle or loss of muscle and people who are going to go you know the wrong direction and i think the data is that it is quite important”

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Nutrition 2:15:38 0
“there are data that show just the protein difference alone can make some difference, but it's not nearly the difference you get when you pair it with hypertrophy training”

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Nutrition 2:17:11 0
“low protein is beneficial up to about 65 years of age and then once you get above 65 years of age it kind of flips and people who ate a higher protein diet have lower all-cause mortality”

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Nutrition 2:19:39 0
“your total mortality benefit was lower eating a high protein diet I think it was starting somewhere in the 60s and that actually surprised me because the relative impact of the high protein diet early in life would have to be an order of magnitude greater than the relative impact of the so I'm sorry say what they're finding was again at the age of I don't remember the exact number it's in the it's in the paper right you can see the curves you can see the curves crossed it was much later than I thought it would be given that 65 was the point that they they kind of picked”

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Nutrition 2:20:37 0
“once you get past 50, the benefit of a high protein diet on mortality seems to outweigh any detriment that you would get from”

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Nutrition 2:21:54 0
“there's a huge difference in muscle mass which we know is going to be associated with frailty”

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Nutrition 2:22:23 0
“we use IGF-1 as a biomarker for protein intake”

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Genetics 2:25:01 0
“mutations that directly affect igf-1 itself and the effects on lifespan”

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Genetics 2:25:13 0
“mutations that reduce growth hormone signaling in mice extend lifespan”

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Genetics 2:25:42 0
“there's one study that that that i think it used a monoclonal antibody to the igf-1 receptor in mice this is from near bars and hosey cohen”

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Hormone balance 2:26:39 0
“i have a lot of patients that are asking to be put on growth hormone”

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Hormone balance 2:28:03 0
“i even took it for a week after my shoulder surgery”

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Hormone balance 2:30:31 0
“I personally have settled around the idea for now at least that IGF-1 particularly is probably not that informative in people particularly you know once you get past 50 years.”

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Hormone balance 2:31:12 0
“Total IGF is not really completely informative as to what's happening even in terms of the quantity that's there for signaling because it's not the unbound portion of it.”

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Nutrition 2:33:09 0
“It's hard for me to draw too much confidence that high protein is significantly detrimental when you're younger than 50.”

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Nutrition 2:33:29 0
“I feel pretty confident that a higher at least certainly higher than the RDA level of dietary protein intake when you're above 50 is beneficial, particularly if you're exercising.”

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Genetics 2:34:48 0
“The interesting things are there's no difference in lifespan, but the people with low levels of growth hormone signaling the reduction in cancer risk is profound.”

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Hormone balance 2:36:28 0
“constitutively low in growth hormone through your entire life”

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Hormone balance 2:38:48 0
“high growth hormone signaling and high igf-1 signaling everything else being equal in a person leads to a higher risk of developing cancer.”

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Hormone balance 2:40:14 0
“if you promote cell division that that is a permissive early environment for mutations to happen and cancers to get a foothold.”

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Nutrition 2:41:47 0
“actually did not dive into the genetic interaction with caloric restriction so i mean i think the take home there is that even in mice where we can control everything else if you look across genotypes you get different results from the same diet and the effect of caloric restriction on lifespan”

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Nutrition 2:42:10 0
“we've learned a ton from these nutritional studies in laboratory animals about the biological mechanisms we've learned a lot about which proteins are and and pathways are important and that has led us to things like rapamycin”

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Nutrition 2:42:45 0
“eating a relatively healthy diet don't worry so much about how much protein how much carbs how much fat eat good foods right don't overeat and be active right exercise”

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Exercise 2:42:45 0
“eating a relatively healthy diet don't worry so much about how much protein how much carbs how much fat eat good foods right don't overeat and be active right exercise”

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Summary of Key Points in Nutrition, Exercise, and Longevity Discussed in Podcast

Nutrition and Longevity

Nutrition’s intricate role in aging and longevity is a recurring subject, with specific focus on caloric and protein intake. Caloric restriction has been consistently highlighted for its potential to prolong lifespan across various species, often emphasizing the relationship between restricted calorie diets and slowed aging processes. Similarly, protein intake is under scrutiny for its effects, varying by age; it’s suggested that lower protein may benefit individuals under 65, while higher intake could be advantageous past this age.

Exercise and Health

Exercise is repeatedly spotlighted as a more beneficial focus than minute dietary optimizations for improving health outcomes. Moderate physical activity levels are proposed to offer substantial health benefits, essential in a balanced approach to wellness.

Genetics and Aging

Discussions extend into the genetic aspects of aging, where factors like growth hormone signaling and epigenetic modifications are considered. The impacts of these genetic components reveal complex interactions with diet and lifestyle, influencing lifespan and health quality.

Metabolic Health

Metabolic health emerges frequently, with ties to dietary habits and caloric intake. Discussions suggest that both caloric restriction and its timing could impact metabolic functions, potentially affecting glucose handling and overall metabolic health.

Risks and Practical Recommendations

While exploring these topics, the conversations tend to offer cautious recommendations rather than definitive guidelines, suggesting that individual responses can vary greatly due to genetic makeup and personal health status. Each strategy, from diet modifications like ketogenic or plant-based diets to fasting and exercise regimens, is considered with an emphasis on tailoring approaches to individual needs and conditions.

Conclusion

The synthesis of these discussions points towards a nuanced view of nutrition and longevity, advocating for a balanced and personalized approach rather than rigid adherence to any single dietary or exercise protocol. This perspective not only underscores the complexity of human biology but also highlights the potential for tailored interventions to enhance health and extend life effectively.