Exploring Metformin's Potential for Longevity and Anti-Aging Benefits

Metabolic health 0:26 0
“Peter is going to discuss a paper on Metformin which is a drug that many people are interested in for its potential role in longevity.”

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Cognitive stimulation 1:53 0
“I present a paper which is about the placebo effect... it shows that the placebo effect can actually follow a dose response.”

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Sleep 3:45 0
“Helix sleep makes customized mattresses to give you the best possible night's sleep.”

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Metabolic health 5:11 0
“throughout the day you want to keep your blood glucose steady without big spikes or dips using levels you can monitor how different types of foods and different food combinations as well as food timing and things like exercise combined to impact your blood glucose levels”

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Nutrition 5:27 0
“I started using levels a little over a year ago and it gave me a lot of insight into how specific Foods were spiking my blood sugar and then leaving me feeling tired for several hours afterwards”

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Exercise 5:37 0
“as well as how the spacing of exercise and my meals was impacting my overall energy”

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Nutrition 10:35 0
“they're drinking yerba mate they drink it usually after their meals supposed to be good for your digestion”

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Mental health 10:54 0
“recently I've been doing some dream exploration I've had some absolutely transformative dreams for the first time in my life one dream in particular that has that allowed me to feel something I've never felt before and has catalyzed a large number of important decisions in a way that no other experience waking or sleep has ever impacted me”

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Substances 13:41 0
“metformin is a drug that has been used for many years uh depends you know where it was first approved I think was in Europe but you know call it directionally 50 plus years of use as a first line agent for patients with type 2 diabetes in the U.S maybe 40 plus years”

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Metabolic health 16:31 0
“the net effect of that is that it changes the ratio of adenosine monophosphate to adenosine diphosphate”

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Metabolic health 16:45 0
“what it unambiguously does is reduces the amount of glucose that the liver puts out”

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Metabolic health 17:30 0
“the difference between being metabolically healthy and having you know profound type 2 diabetes is one teaspoon of glucose in your bloodstream”

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Metabolic health 19:54 0
“the primary insult probably occurs in the muscles and it is insulin resistance”

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Metabolic health 22:06 0
“that is the definition of insulin resistance the cell is becoming resistant to the effect of insulin and therefore the early Mark of insulin resistance the canary in the coal mine is not an increase in glucose it's an increase in insulin so normal glycemia with hyperinsulinemia especially postprandial meaning after you eat hyperinsulinemia is the thing that tells you hey you're five ten years away from this being a real problem”

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Exercise 24:42 0
“exercising is one of the most important things you're going to do to ward off insulin resistance”

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Sleep 24:52 0
“sleep deprivation has a profound impact on insulin resistance”

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Substances 25:32 0
“enter metformin first line drug so most of the drugs so every drug you give a person with type 2 diabetes is trying to address part of this chain so some of the drugs tell you to make more insulin that's that's one of the strategies so here are drugs like sulfona ureas they tell the body make more insulin other drugs like insulin just give you more of the insulin thing metformin tackles the problem elsewhere it tamps down glucose by addressing the glucose the hepatic glucose output channel”

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Substances 28:01 0
“so clearly metformin has this side effect initially which is a little bit of appetite suppression but regardless that's the story on Metformin there are a lot of reasons I was interested in it”

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Disease prevention 28:16 0
“what I was thinking is hey this is going to help you buffer glucose better it's got to be better”

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Disease prevention 28:53 0
“a pcsk9 inhibitor is sort of zero protective but it's targeting one specific pathway which is cardiovascular disease and dyslipidemia”

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Disease prevention 33:00 0
“the banister study found a very interesting result which was the crude death rate um was and by the way the way these are done this is also one of the challenges of epidemiology is the math gets much more complicated”

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Metabolic health 33:41 0
“if you look at the control group it was 15.2 this was a startling result and I remember reading this in again 2014 and being like holy crap this is really amazing”

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Metabolic health 34:53 0
“the people who took metformin and had diabetes had a 15 one five fifteen percent relative reduction in all-cause death over 2.8 years which was the median duration of follow-up”

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Nutrition 36:31 0
“I try to get enough servings of vitamins and minerals through whole food sources that include vegetables and fruits every day but oftentimes I simply can't get enough servings but with ag1 I'm sure to get enough vitamins and minerals and the probiotics that I need”

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Disease prevention 40:00 0
“the tame trial which is an important trial is going to try to ask this question prospectively and through random assignment so so this is the targeting aging with metformin trial that's correct.”

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Genetics 41:15 0
“they did a second analysis in parallel with discordant twins so same-sex twins that only differed in that one had diabetes and one didn't.”

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Disease prevention 45:34 0
“The Singletons with without so the non-twins who were not diabetic it was 16.86 and could you put a little more Contour on what this thousand person years what what it is are you talking about pooling the lifespans of a of of a bunch of different people until you get to the number 1000.”

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Disease prevention 48:39 0
“When you adjust for age a very important check to do is what is the crude death rate of the people on Metformin who are not twins versus who are twins now in this table they look different because it's 24.93 for the metformin group and 21.68 for the twin group in that's on Metformin when you adjust for age they're almost identical it's it goes from 29 point 24.93 to 24.71.”

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Disease prevention 52:39 0
“you have two lines you have those that were on Metformin with type 2 diabetes and you have their matched controls and in this figure the Matched controls are the darker lines and the people with type 2 diabetes on Metformin that's the lighter line”

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Disease prevention 53:23 0
“the people who are taking metformin that have diabetes are dying at a faster rate for every single year”

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Disease prevention 57:19 0
“P less than 0.05 tends to be the kind of gold standard cut off.”

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Disease prevention 58:01 0
“Statistical power is a very important concept that probably doesn't get discussed enough but before you do an experiment you have to have an expectation of what you believe the difference is between the groups and you have to determine the number of samples you will need to assess whether or not that difference is there or not.”

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Disease prevention 59:56 0
“Increasing sample size tends to decrease variation.”

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Disease prevention 1:03:04 0
“if the number is negative you may recall on the banister paper the hazard ratio was 0.85 so if it's nothing so that means it's a 15 reduction in relative risk”

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Disease prevention 1:03:36 0
“the people on Metformin had a 48 greater chance of dying in any given year than their non-diabetic counterpart”

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Disease prevention 1:06:13 0
“if you do the twin study which you could argue is a slightly pure study because you at least have one genetic and environmental thing that you've attached the unadjusted model is brutal 2.15 that's a hundred and fifteen percent”

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Metabolic health 1:09:02 0
“the keys paper makes it undeniably clear that in that population there was no Advantage offered by metformin that undid the disadvantage of having type 2 diabetes”

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Nutrition 1:11:03 0
“virtually every study that compares meat eaters to non-meat eaters finds an advantage amongst the non-meat eaters”

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Substances 1:13:48 0
“the ITP was the first study that really put rapamycin on the map in 2009 that was the study that's fortuitously demonstrated that even when rapamycin was given very very late in life it was given to 60 month old mice it still afforded them a 15% lifespan extension”

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Substances 1:14:13 0
“when the ITP studied metformin it did not succeed”

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Hormone balance 1:15:04 0
“males we're talking post-puberty should try and have their estrogen as high as possible without having negative symptomology because of the importance of estrogen for libido, for brain function, tissue, bone health”

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Metabolic health 1:16:22 0
“once I got really into lactate testing I noticed how high my lactate was at rest so a resting fasted lactate should be in a healthy person should be below one like somewhere between 0.3.6 millimole and only when you start to exercise should lactate go up”

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Nutrition 1:18:57 0
“the only modification I made to this slow carb diet for our body thing was the day after the cheat day I wouldn't eat I would just fast and I had no problem doing that because it was just basically well since you said um uh what was it anal um analc was I did not have that but since you said that I um I won't up the ante here but I'll at least match your anal seepage comment by saying I had let's just call it profound gastric distress after eating like that the next day so the last thing you want to do is eat any food I'll just hydrate and oftentimes to try and get some exercise”

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Substances 1:19:32 0
“what I read was that berberine Poor Man's metformin could buffer blood glucose and in some ways make me feel less sick when ingesting all these calories in in many cases um spiking my my blood sugar and Insulin um because you're having ice cream and you know Etc and indeed it worked so if I took berberine and I don't recall the milligram count and then I ate you know 12 donuts I felt fine it was as if I had eaten one donut wow I felt sort of okay in my body and I felt much much better now”

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Substances 1:20:18 0
“one thing I noticed was that if I took berberine and I did not ingest a profound number of carbohydrates very soon afterwards I got brutal headaches I think I was hypoglycemic I didn't measure it but I just felt I had headaches I didn't feel good and then I would eat a pizza or two and feel fine”

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Substances 1:21:09 0
“a carbos is another glucose disposal agent that actually found a survival benefit in the ITP and it was a very interesting finding because the the thesis for testing it the ITP is a very clever system anybody can nominate a candidate to be tested then the you know the panel over there reviews it and they decide Yep this is interesting we'll go ahead and study it”

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Nutrition 1:24:18 0
“energy balance and buffer glucose with good sleep hygiene lots of exercise and just thoughtful eating without having to go into a calorie deficit”

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Nutrition 1:26:05 0
“I'm a Believer in getting most of my nutrients from unprocessed or minimally processed sources simply because it allows me to eat Foods I like and more of them and I just love to eat.”

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Nutrition 1:28:10 0
“do you think there's any longevity benefit to short periods of caloric restriction”

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Nutrition 1:26:02 0
“I don't think that the specific macros matter as much as I used to think.”

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Exercise 1:30:53 0
“when you lift weights you can look at how much weight you're lifting you can look at your dexa scan and see how much muscle mass you're generating like those are biomarkers those are giving you outputs that say my input is good or my input needs to be modified”

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Sleep 1:31:06 0
“when you take a sleep supplement you can look at your eight sleep and go oh my sleep is getting better like there's a biomarker”

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Stress management 1:41:20 0
“Placebo effects are real, we know this belief effects are not a or b Placebo or non Placebo belief effects have a lot of knowledge to enrich one's belief about a certain something that can shift their Psychology and Physiology one way or the other.”

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Stress management 1:42:32 0
“you take a different group of people and randomly assign them to another group where now they're being told that stress enhances performance, it mobilizes resources it Narrows your vision such that you can perform tasks better Etc et cetera and their performance increases above a control group that receives just useless information or at least useless as it relates to the task.”

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Nutrition 1:43:38 0
“you give people a milkshake you tell it's a high calorie milkshake has a lot of nutrients and then you measure ghrelin secretion in the blood and ghrelin is a marker of hunger that increases the longer it's been since you've eaten and what you notice is that suppresses ghrelin to a great degree and for a long period of time you give another group a shake you tell them it's a low calorie Shake that it's got some nutrients in it but doesn't have much fat not much sugar Etc they drink the shape less ghrelin's suppression and it's the same shake.”

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Cognitive stimulation 1:45:53 0
“nicotine is cognitive enhancing why well you have a couple sites in the brain namely in the basal forebrain nucleus basalus in the back of the brain structures like Locus ceruleus but also this what's called it's got a funny name the pedunculopontine nucleus which is this nucleus in the in the the pons in the back of the brain in the brain stem that sends those little axon wires into the thalamus the thalamus is a gateway for sensory information and in the thalamus the visual information the auditory information it has nicotinic receptors and when the pedunculopontine nucleus releases nicotine or when you ingest nicotine what it does is it increases the signal to noise of information coming in through your senses so the Fidelity of the signal that gets up to your cortex which is your conscious perception of those senses is increased”

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Cognitive stimulation 1:47:55 0
“for instance and that's really what acetylcholine does that's why when people smoke a cigarette they get that boost of nicotine and they just feel clear it really works”

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Substances 1:51:18 0
“typically there's a washout before they come in so they're not smoking for a bit so they can clear their system of nicotine and they measure how long is that needed um typically it's a couple of days.”

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Substances 1:51:45 0
“they have them vape and they're vaping either a low medium or high dose of nicotine the dosages don't really matter because tolerance varies Etc”

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Substances 1:56:50 0
“these groups were given a vape pen prior to this where they've Vaped what they were told is either a low medium or high dose of nicotine and they do this task”

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Substances 1:57:42 0
“they measured people's belief as to whether or not they got low medium or high amounts of nicotine and if they were told they got either this is a low amount a medium amount or a high amount”

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Substances 1:59:01 0
“if you look at the activation of the thalamus in the exact regions where you would predict acetylcholine transmission to impact the function of the thalamus so these include areas like What's called the centromedian nucleus the ventral posterior nucleus the names that really don't matter but these are areas involved in attention”

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Substances 1:59:21 0
“it scales with what they thought they got in the vape pen meaning if you were told that you got a low amount of nicotine you got a little bit of activation in these areas if you were told that you got a medium amount of nicotine and that's what you Vaped then you had medium amounts or moderate amounts of activation and if you were told you you got high amounts of nicotine you got a high degree of activation”

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Substances 2:02:12 0
“the belief about nicotine strength induced a dose dependent response in the thalamus”

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Substances 2:02:54 0
“if I tell you this is a high dose of nicotine your brain will react as if it's a high dose of nicotine”

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Substances 2:03:37 0
“what we are told about the dose of a drug changes the way that our physiology responds to the dose of the drug”

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Substances 1:28:36 0
“if you look at figure 3B other people can't see it but basically oh yeah what you'll see is that there's no difference between these different groups um in terms of the amount amount of activation in these reward Pathways if people got a low medium or high amount of nicotine.”

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Substances 1:28:54 0
“this actually could be leveraged I believe if somebody were trying to quit nicotine for instance and they were going to do that by progressively reducing the amount of nicotine that they were taking but you told them that it was the same amount one from one day to the next you could Whittle it down to presumably to a low amount before taking it to zero and if they believed it to be a greater amount then it might actually not uh disrupt their reward Pathways meaning they would feel presumably they'd feel rewarded by whatever nicotine they were bringing in.”

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Substances 2:12:46 0
“there's no quicker way to make a mouse overeat or under eat than by lesioning it's hypothalamus depending on where you do so so presumably these drugs work there”

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Substances 2:13:06 0
“those drugs have all been tested via Placebo and the placebo groups you know don't do anywhere near as well that's how we know that there's activity of the drug”

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Mental health 2:13:58 0
“the lower dose may be as effective simply on the basis of belief”

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Mental health 2:14:29 0
“your brain is a prediction making machine it's a data interpretation machine but it's clear that one of the more important pieces of data are your beliefs about how these things impact you”

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Overview of Metformin’s Role in Metabolic Health and Longevity

Understanding Metformin’s Mechanism and Effectiveness

In medical discussions and studies, Metformin, a widely recognized drug for managing type 2 diabetes, has been investigated for its benefits beyond glucose regulation, particularly its role in prolonging life. Its function primarily includes reducing glucose production by the liver, one of the essential mechanisms for controlling blood sugar levels in diabetic patients.

Metformin’s Role in Longevity Research

Recent discussions and research have shifted towards Metformin’s potential in anti-aging and longevity, shedding light on its secondary effects which might extend human life expectancy. A significant body of research underscores Metformin’s capacity to minimize complications associated with metabolic diseases, hinting towards its extended benefits in healthy individuals as a prophylactic agent.

Broadening the Understanding through Clinical Trials

Clinical trials like the TAME (Targeting Aging with Metformin) trial have been pivotal in attempting to understand how Metformin can impact aging at a molecular level. These trials aim to provide a structured analysis and clear results on whether Metformin could be officially recommended for the aging population.

Comparative Studies and Meta-Analysis

In addition to targeted trials, numerous comparative studies have been undertaken to observe Metformin’s effects on non-diabetic populations, analyzing its safety and efficacy. Some studies have reported a decrease in mortality rates among Metformin users compared to non-users, though these results are sometimes contradicted by other reports suggesting minimal to no significant improvement in longevity metrics.

Pharmacological Insights and Recommendations

Pharmacologically, Metformin is considered relatively safe with minor side effects like gastrointestinal upset. It’s these manageable side effects, combined with the drug’s potential benefits, that make it a candidate for re-purposing in the context of aging and longevity. However, without conclusive, universally accepted research outcomes, the widespread use of Metformin solely for anti-aging remains cautious.

Future Directions and Considerations

The ongoing research, debates, and discussions continue to push the boundaries of how traditional medications can be utilized for new, innovative purposes, transcending their original intentions. As Metformin continues to be a subject of intensive study, the scientific community remains hopeful yet prudent, awaiting more robust data to advocate broader uses of this conventional medicine beyond the diabetic spectrum.