Enhancing Longevity and Health with Immune-Boosting Substances Research Insights

Genetics 0:55 0
“he has spearheaded one of the most impressive longevity gene projects which basically looked at more than 500 healthy people aged 95 to north of 110 along with following their offspring the centenarian studies in the centenarian offspring study”

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Substances 1:38 0
“the two drugs i get asked about more than all other drugs combined namely metformin and rapamycin or the category of analogues to rapamycin known as rapalogs”

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Disease prevention 2:03 0
“their potential for reducing the risk of saros cov2 infection or other infections and of course covet 19 morbidity”

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Substances 6:36 0
“Novartis had a rapamycin analog and there was a lot of data that mTOR inhibitors have beneficial effects on aging and lifespan.”

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Immunizations 6:54 0
“So I decided let's do a trial and see if we give older adults an mTOR inhibitor can we make their immune function better and the readout was a vaccine response to a flu vaccine.”

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Substances 9:42 0
“It was because of all the data that mTOR inhibition has beneficial effects on aging and every organism tested.”

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Immunizations 12:36 0
“older mice given rapamycin that vaccination response was improved”

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Substances 13:16 0
“we used very unusual dosing regimens of this rapamycin analog that we either dosed at a very low dose once daily or once weekly”

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Immunizations 13:52 0
“if you gave it one of these mTOR inhibitors for six weeks and then gave people a two week break and gave them a flu vaccination they responded better to the flu vaccination”

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Substances 17:24 0
“the people on metformin who were diabetic were more obese had more diseases to start with had significantly less mortality”

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Substances 20:30 0
“in the metformin study in males in one center they lived ten percent longer in one also ten one was nine one was eleven or something like that in one center it was one percent less”

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Substances 21:01 0
“when they added rapamycin to metformin to rapamycin you could say if you think metformin has no effect that was that was cohort seven that was a nine-month intervention or they were they treated the mice at nine months with metformin and rappa together”

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Substances 21:23 0
“the nice thing of being young like you is that uh you recall those numbers they're seven eleven that's the longest living animals I think so far in this ITP they live 24 longer”

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Substances 21:48 0
“and i should add it wasn't studied at the same time okay so you can say there's a cohort effect”

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Substances 23:11 0
“we probably have more than enough information of the power of this intervention in humans that it's a little bit of the tail wagging the dog if we're gonna get wound up about which strain of mice does better on metformin or not”

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Metabolic health 26:50 0
“metformin let's say on the cellular level it fixes aging 26:53 okay once it fixes aging a lot of things 26:56 improve okay maybe the fact that insulin 27:00 levels go down doesn't have to do only 27:04 with metformin effect on glucose but 27:05 because 27:07 autophagy has increased mitochondrial 27:09 function is better 27:10 genetic stability is good you know 27:12 things like that”

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Metabolic health 30:19 0
“big pillar one is the metabolic complex 30:23 one ampk mtor pathway 30:28 right which is what we just discussed 30:30 the second 30:31 is there is a decrease in oxidative 30:35 stress in 30:36 rose production and therefore 30:39 also on dm dna damage that is the 30:42 consequence 30:43 of using a low dose of a 30:47 mitochondrial poison right so there's 30:50 this 30:50 aspect of that and the third aspect 30:53 the relationship to autoin to 30:57 immune function and inflammation”

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Disease prevention 34:53 0
“delaying the onset of cancer is an important pillar of longevity”

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Immunizations 36:01 0
“one of the factors and how you respond to a vaccine is actually innate immunity”

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Disease prevention 35:19 0
“there's a non-trivial chance that a 75 or 85 year old person is going to die from an influenza virus”

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Disease prevention 39:40 0
“there are papers in the 40 and 50s on baiguanids that were actually looking like metformin remember the history of metformin it had a cousin fenforming that seems to be more active against diabetes but it was associated with lactic acidosis so they went back to metformin but in the 40s and 50s and 60s metformin was used around the world for influenza in the elderly and there's a lot of literature unfortunately the literature is in czech and swedish and philippines and i'm not starting to get a lot of translation but all of them were positive response to using metformin as an immune enhancer against the flu by the way against malaria and some other indications”

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Disease prevention 40:47 0
“we knew that patients with type 2 diabetes if they get metformin they immunize better against the flu there is a at least a study like that”

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Disease prevention 43:08 0
“there's a paper that was published in china a little bit more than a week ago where they looked at the 100 people with kovid that were treated with metformin comparing them to the 178 people that were diabetic and treated and not treated with metformin”

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Disease prevention 45:49 0
“really the issue with influenza is that it can paralyze the immune system and it's these secondary infections that come in.”

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Disease prevention 46:22 0
“there was a paper that came out from the CDC in New England Journal in 2015 that looked at what actually causes pneumonia in the elderly that gets them hospitalized and it's not a combination of virus and bacteria that is some of it but the majority is a virus and the most common virus is actually rhinovirus which is the cause of the common cold.”

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Disease prevention 47:56 0
“the coronavirus infects cells including lung cells and that causes direct damage from the virus but then the host response to the virus is good because it will get rid of the virus but if it gets excessive you'll get cytokine storm which will cause major life-threatening consequences independent of the virus.”

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Disease prevention 49:25 0
“in people who get mTOR inhibitors their innate antiviral gene expression is enhanced when they get a viral infection so what this suggests is early on like as post-exposure prophylaxis or pro in a prevention mode the mTOR inhibitors may have benefit by boosting the body's response that is defective as we get older to the virus so we can clear it better.”

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Disease prevention 52:18 0
“but even more important they had 80 decrease in peripheral in plasma tnf alpha levels that was also highly significant”

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Disease prevention 53:58 0
“less people in metformin are hospitalized so they get their immunities better right and then when they're in their hospital less of them go into an inflammatory response”

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Disease prevention 57:11 0
“mtor inhibitors may interact directly with covid and inhibit replication both meaning the virus the sars virus”

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Disease prevention 59:56 0
“we noticed that the people who were getting the amter the rapalog were reporting fewer respiratory tract infection as adverse events and they weren't flu they were just all common respiratory tract infections”

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Disease prevention 1:00:29 0
“in our face tube we said let's not only look at vaccine response but let's actually look at infections that occur to see are we decreasing infection rates”

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Disease prevention 1:03:56 0
“in both studies rtb alone decreased respiratory tract infections and in one the combination did and the other it didn't”

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Disease prevention 1:05:08 0
“I think what the mTOR inhibitors are doing is not stopping people from getting infected but if you get infected there's a better immune response and your symptoms will be milder.”

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Disease prevention 1:08:02 0
“We are reinforcing we're not fighting the virus we're reinforcing the host.”

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Immunizations 1:09:07 0
“The vaccines that I'm seeing developing are not considering the older host in several ways.”

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Disease prevention 1:11:03 0
“so we now have a fifth coronavirus that's here to stay except unlike its other four cousins this one can really whack you”

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Immunizations 1:11:11 0
“let's assume we can make some safe and efficacious vaccines are they really likely to keep you protected for five years ten years or more even without the genetic drift”

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Immunizations 1:11:41 0
“it means we need a better strategy around immune enhancement”

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Disease prevention 1:13:52 0
“the nice thing about covid19 is it's making it obvious why enhancing immune function is a really important area”

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Substances 1:17:56 0
“Joan, I started taking metformin in 2010, that's when I sort of became pretty convinced about the data. I started taking rapamycin in 2018, it's been about two years.”

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Substances 1:18:37 0
“The reason I chose metformin, it's not because it was the best drug, I think rapamycin should be a better drug but it's because we didn't want to kill anyone on the road to success.”

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Substances 1:20:25 0
“Metformin as you said is a free drug effectively, who has a financial interest in this? There's no drug company that could be interested in this right, it has to be sort of philanthropic or NIH driven.”

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Immunizations 1:25:09 0
“if we start before immunization will immunize for influenza the first year and see the response and then for COVID-19 the next year and see the response”

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Exercise 1:28:05 0
“in 2018 i started to very very closely track my lactate levels during exercise and in particular i was tracking my lactate levels during a type of exercise called zone 2 exercise which is when you're basically trying to see how much work you can do under purely aerobic conditions”

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Exercise 1:30:15 0
“everybody exercised half of them with metformin and half without”

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Exercise 1:30:32 0
“the people that were exercising with metformin had significantly less muscle mass”

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Exercise 1:30:54 0
“gram of muscle when you're on metformin is doing better work than gram of muscle when you exercise only”

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Exercise 1:32:47 0
“all our patients increased their lactic acid some of them above two some of them below two”

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Exercise 1:32:54 0
“the increase in lactic acid was associated with better glucose control”

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Oral hygiene 1:36:07 0
“don't think i went more than two weeks without a horrible aptos ulcer in my mouth during my residency”

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Substances 1:36:15 0
“never getting one again until i started rapamycin you know 12 14 years later that's been the only thing i've noticed”

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Substances 1:36:24 0
“one other little thing i've noticed which is really odd is when i'm on it, it's not surprising my fingernails grow slower”

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Nutrition 1:38:16 0
“the elderly animals are before the body weight were separated in parallel and all of a sudden the monkeys are older but they're starting to weigh the same although they're calorically restricted supposedly”

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Genetics 1:42:08 0
“methylation is one way where the environment interacts with our genome and the methylation with aging are either increasing or decreasing both of them happens and they very often the consequences change in a gene activity”

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Genetics 1:42:29 0
“David Sinclair in his book you can see that I'm seeing it as one of the hallmarks of aging David Sinclair really thinks that that's not only the major cause of aging but also the major way we changed it”

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Genetics 1:42:48 0
“Horvat and Morgan Levine and some other people around the world have looked at methylation sites and tried to correlate them to chronological age”

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Genetics 1:43:25 0
“Methylation clocks are good, they're really good clocks of biological age in particular when you see if they predict mortality for example but also prediction of a lot of diseases”

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Nutrition 1:49:11 0
“they took patients and gave them a growth hormone, metformin and dhea”

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Genetics 1:49:28 0
“i'm doing lots of methylation on my centenarians and their children”

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Metabolic health 1:49:39 0
“we've done some of this at Novartis with proteomics and aging and the problem is some of the proteins that go up with age are actually they've been shown in the Framingham Heart Study to be beneficial”

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Genetics 1:50:58 0
“the gender effects of aging are so incredible and we've missed them in every model”

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Genetics 1:55:41 0
“the offspring inherited only half of their genetic makeup right but they're so much healthier than control”

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Disease prevention 1:59:52 0
“we have to attack the virus and we have to defend the host”

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Immunizations 1:59:59 0
“you have joan who's telling you very convincingly of many studies that showed that immunity was improved”

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Metabolic health 1:59:34 0
“i prescribe metformin to my patients some who need it for the standard indication of hyperglycemia hyperinsulinemia but a number who say look peter i've read enough of your stuff i've listened to enough of your podcasts i want to take metformin for these other benefits”

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Sleep 2:03:58 0
“why hasn't someone done the definitive study to test the effect of sleep on immune function i mean really let's put this to rest and be done with it does it matter if you get eight hours versus six hours of sleep and if so how much does it matter”

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Disease prevention 2:02:10 0
“we should always have a national stockpile of ppe we should have a national stockpile of every reagent you would ever want to do pcr we should have a national stockpile of any form of antiviral therapy or immune modulating therapy that could be effective”

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Substances 2:07:20 0
“I think for metformin what needs to be considered is that TAME will answer some of the questions.”

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Disease prevention 2:11:02 0
“The FDA's never had a drug to give immuno resilience and decrease all sorts of infections so they'd have to figure it out.”

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Disease prevention 1:33:48 0
“imagine you could three months into a study have a biomarker that tells you you're on the wrong direction you're on the right direction you need to pivot you have a phase three design that is flexible enough to allow you to make the dose change or take a certain population out of the study”

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Most important takeaways of the video

  1. A longevity gene project led by Near Barzilai involved over 500 healthy individuals aged 95 to over 110, along with their offspring, to study genetic factors contributing to exceptional lifespan.
  2. Metformin and rapamycin are frequently discussed substances in the context of longevity, health, and disease prevention, with potential roles in reducing the risk of COVID-19 and other infections.
  3. Clinical trials have explored the potential of mTOR inhibitors in enhancing immune function, improving vaccination responses, and reducing respiratory tract infections.
  4. Research suggests that metformin may have broader health benefits beyond its standard indication for hyperglycemia, including potential immune-enhancing effects and reduced hospitalization rates.
  5. Biomarkers play a crucial role in early detection and

Overview of Peter Attia’s Discussions on Longevity and Substances

Genetic Studies on Longevity

Dr. Nir Barzilai has conducted significant research on longevity through genetic studies involving over 500 healthy individuals aged 95 to over 110 and their offspring. This study highlights the genetic components contributing to an exceptional lifespan.

Impact of Substances on Longevity and Disease Prevention

Peter Attia frequently discusses the role of substances like metformin and rapamycin, and their analogs (rapalogs), noting their potential in enhancing longevity and health. Metformin and rapamycin have been shown to possibly reduce the risk of infections including COVID-19 and influence immune responses positively. Specifically, metformin has been observed to lower mortality in diabetic patients despite their higher predisposition to comorbidities.

mTOR Inhibitors and Immunization

Clinical trials have been conducted to explore if mTOR inhibitors can enhance immune function in older adults. The trials measured the efficacy of influenza vaccinations as a response metric, and findings suggested improved immune responses due to the mTOR inhibitors. These studies align with animal studies where rapamycin enhanced the vaccination response in older mice.

Metformin: Beyond Diabetes

Historically, metformin was used globally not just for diabetes but as an immune enhancer against influenza and other diseases. Recent studies continue to explore metformin’s protective effects against severe COVID-19 outcomes in diabetic patients and its potential use as a prophylactic treatment due to its immune-modulating properties.

Research on Aging and Metabolic Health

Discussions extend to the metabolic effects of substances like metformin which involves pathways like AMPK and mTOR. Metformin is suggested to improve cellular aging, which sequentially enhances various metabolic functions such as reduced insulin levels, increased autophagy, and improved mitochondrial function.

Substance Dosing in Research

The dosing regimens of substances like rapamycin analogs were carefully manipulated in studies to observe different impacts on aging and immune function. For instance, low doses administered daily or weekly showed different effects compared to more frequent dosages, providing valuable insights into the dosage-dependent effects of these substances on longevity and health.

Implications for Future Research and Treatment

The evidence gathered from various uncited studies and clinical trials suggests a promising frontier in using these substances not only for treating diseases but potentially for prolonging the healthspan. Continuous research and carefully designed trials are imperative to further understand and harness these benefits effectively.