Insights on Enhancing Lifespan Through Anti-Aging Interventions and Research

Substances 0:09 0
“we have great evidence now for at least three mutants and the calor restriction diet and the methionine restriction diet and we're getting there for rapy and several of the other drugs that came along”

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Substances 2:17 0
“we try to find drugs that will slow aging and extend Mouse lifespan”

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Substances 4:33 0
“we found uh a couple years ago that a a drug capap Pro which is FDA approved in in people for blood pressure kind of to my surprise gave a really small increase in lifespan in mice”

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Genetics 12:12:25 0
“there's a set of collaborators including Rob Williams at Tennessee and Johan Al in Switzerland uh which have taken these mice we've given them uh this point something like 12,000 Tales 20 12,000 DNA samples from mice that have a known lifespan and they have already published a paper it came out last year in science and there's another one in the pipeline now that says oh look here's a gene that tells you how long the females will live here's a gene that tells you how long males and females will live here's a gene that tells you how long you live but it only counts if you've made it past the midpoint it only works on the oldest half of the mice”

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Genetics 13:26:00 0
“not only are they identical, they are homozygous that means that the gene they got from their mother and the gene from the father are the same so it's like an inbred form of homozygosity that we can't we don't even have a human phenotype that is that inbred.”

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Disease prevention 17:45 0
“the proportional Hazard that is the risk of death over the whole lifespan which is to the closest easily understood term is the median lifespan”

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Disease prevention 18:08 0
“if half of the mice in the normal group um died by 800 days and in the drug treated group half of the mice were still alive on day 880, that's 80 days later then that's a 10% increase in lifespan”

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Disease prevention 18:53 0
“we wait until 90% of the mice are dead in both populations the control and the treated population and then on the date when the 90% Mouse dies we say what fraction of the mice are in the treated group of the ones that are alive”

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Environment 25:57 0
“males at Michigan always live 5 to to 10% longer than males at the other two sites that's unexpected and problematic and we really don't understand it maybe it's the water tastes funny or there's some smell that the mice can are obsessed about that we don't know about or there's um some contamination in the Sonic environment that is sight specific”

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Body weight 26:38 0
“the Michigan mice are always controls are about 10% lighter both in males and females than mice at the other two sites”

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Substances 31:11 0
“the famous One the early one was rap ayin about 90% of the Romy that was given to mice in the food never made it into the mouse because it's digested in the stomach and the acid conditions of the stomach it gets degraded”

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Substances 31:26 0
“Randy with colleagues of his uh worked out a way to encapsulate the Romy in a capsule plastic capsule that makes it through the stomach and dissolves in the more alkaline conditions of the small intestine.”

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Substances 32:20 0
“the Texas group showed that the blood concentrations are three-fold higher in females than in males”

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Nutrition 35:45 0
“in addition monitoring the actual amount of food a mouse eats is a fiction no one can really do it um they they can put a number down and get into the paper but it's it's a fictitious number and the reason is that mice chew their food and leave a lot on the cage on the floor of the cage so you don't know how much food the mouse has actually gotten into itself because you haven't measured little crumbs on the cage floor”

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Disease prevention 37:25 0
“if you had a cure for cancer in people no one over the age of 5050 ever got cancer again median lifespan of humans would go up by 3% and the same is true if you had a drug that abolished heart attacks no one over the age of 50 ever got a heart attack again uh median lifespan for people would go up by less than 3%”

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Substances 36:51 0
“Rapa, in our 2009 paper had a really big effect, we picked a dose that seemed like it might work and it did it's not the optimal dose it's less than the optimal dose but it's the dose we chose both males and females had a significant lifespan extension”

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Metabolic health 41:40 0
“why the acaros has such a big effect in males and a small significant but small effect in females is unknown it presumably has to do with males being more sensitive to high glucose levels a carbos probably works by limiting very high glucose levels”

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Substances 42:08 0
“our you know cytochrome p450 system as humans must have sex differences”

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Substances 45:57 0
“what rap mice and appears to do in their model is increases the production of B cells from the bone marrow so the mice would respond to influenza vaccine and then they were exposed to live virus and they survive”

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Substances 47:29 0
“when Randy finally with his colleagues figured out how to make the protected version the encapsulated version rapid mice and we actually used it twice the same batches some of it went to the mice that were already 20 months of age so we wouldn't have to throw them out and then we executed we gave the rest to the young mice that had been produced in the following year um expecting that the old mice it would fail the young mice it might work and as as you know it worked well in both ages”

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Disease prevention 48:40 0
“starting as late as 20 months of age does not diminish the um uh ability of the drug to extend lifespan”

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Cognitive stimulation 52:07 0
“we're going to be treating mice with these drugs and in addition to looking at their lifespan test them for cognition”

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Metabolic health 54:04 0
“Randy strong and his colleagues were interested in glucose control and glucose homeostasis so the stage two stuff that was done at Texas always had some taste of that.”

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Disease prevention 54:26 0
“here's what's happening in the liver but look it didn't happen in the drug treated mice here's what's happening in the gut but look it didn't happen in the drug treated mice”

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Genetics 57:21 0
“Steve horbath I think is well established and does lovely work, Steve has asked for tissues and we have sent him tissues and we've explained to anybody else who is working on some aspect of either Global or localized tissue specific epigenetic change we'd be delighted to send them tissues.”

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Disease prevention 1:01:19 0
“we have nine published and one unpublished slow aging mice we have four genetic mutants the Snell the growth home receptor knockout the as dwarf and the Pape we have a famous diet calorie restriction and we have at least four well vetted drugs uh a carbos kagos and 17 Al estrad and rap”

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Metabolic health 1:03:15 0
“one of these is ucp1 uncoupling protein one it's a mitochondrial protein that allows your mitochondria to burn fat without doing a lot of work it just turns the fat into heat it's involved in thermogenesis and it's long been known that having a lot of ucp1 um is something happens when you do exercise exercise increases ucp1 and mice that have a lot of ucp1 live a long time so it's thought to play a major role in protecting you from obesity from diabetes from metabolic syndrome from some sorts of inflammation”

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Exercise 1:06:36 0
“ucp1 is changed by chronic exercise um and that's one of the reasons why it's thought to be amongst the mediators of the health benefits that tribute in people and in mice to to exercise.”

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Stress management 1:09:13 0
“their adrenaline level goes up as you can imagine their glucose doubles their blood becomes acidic right the pH drops so we would never want to do that because who knows what's that what is that doing to all the protein kyes and the metabolites anything that is glucose or hormone sensitive is gone going haywire there.”

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Exercise 1:13:10 0
“if you exercise gpld1 goes up, it's true for mice it's true for people and more exciting even than that if you have gpld1 go up cognition goes up”

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Cognitive stimulation 1:13:26 0
“if you have gpld1 go up cognition goes up”

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Genetics 1:18:21 0
“the DNA can be transcribed into messenger RNA that has the same sequence more or less and encodes proteins.”

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Genetics 1:20:08 0
“many of the differences between the neurons and the skin cells and the blood cells and the liver cells are because they express different messenger RNAs from the same DNA template.”

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Genetics 1:21:22 0
“the default presumption which turns out to be wrong is that once you've got those RNAs out there because of transcription into the mRNA the rest is automated they just churn out proteins based upon the RNA that they've got.”

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Genetics 1:21:48 0
“there are now lots of studies that say the idea that the set of proteins depends only on what mRNA you've got is really a poor approximation.”

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Genetics 1:26:05 0
“you used these 10 known cases of slower aging right so four genetic mutations that result in slower aging”

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Substances 1:26:21 0
“five drugs it's actually four four drugs published one is actually another mutant”

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Substances 1:27:30 0
“if you give a drug to a mouse how long does it take for the Aging rate indicators to switch”

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Genetics 1:28:57 0
“if you take these as dwarf mice they're mice that have very low growth hormone very low igf1 and they live 40% longer”

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Exercise 1:32:24 0
“if you wanted to know if this type of exercise routine versus that type of exercise routine this type of diet versus that type of diet or your home brew of Romy versus not is having a benefit at some level we will need to get this out of plasma”

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Exercise 1:33:45 0
“our prediction is that amongst the 7-year-olds the really fit ones will be the ones that look as though they have always had youthful aging rate indicators”

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Exercise 1:37:11 0
“we measure fndc5 as a protein in muscle and we measure irisin as a peptide or protein in the plasma and they always in our hands go up and down together all the slow aging mice have more of the protein in the muscle and more of the irisin in their blood”

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Exercise 1:37:44 0
“the promise of the paper was we now have the exercise drug right it was we're going to we're going to just give people an exercise pill”

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Exercise 1:38:02 0
“gpld1 in a pill is is something that someone's going to think hey that's got to be a good thing”

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Exercise 1:40:10 0
“pharmaceutical companies thrilled with what OIC and its competitors are doing have devoted tons of money to figuring out whether they can get something like Iris into you in a way that doesn't hurt you and does you some good”

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Substances 1:43:55 0
“but we have great evidence now for at least three mutants and the calor restriction diet and the methionine restriction diet and we're getting there for rapamycin and several of the other drugs that came along you know five years eight years after that so I think there will be a very strong case that these drugs are acting by slowing the aging process and delaying maybe not quite all but maybe all of the aspects of Aging that make people unhappy about getting older.”

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Hormone balance 1:50:25 0
“the 17 Alpha estradi is just the same chemically as the 17 beta except for one of the bonds instead of pointing up out of the plane points down in the opposite direction so it's a stereoisomer same chemical formula all the atoms are attached in the same place it's just that two of them are pointing up instead of pointing down and because of that manipulation it doesn't bind very well to the traditional as famous estrogen receptors so it's doing something it's got to be binding to something but it it probably is not the traditional estrogen receptors or it might be that plus something else to get um an effect on estrogen sensitive tissues you can do it with 17 alest you just have to use a lot more I think tenfold more is what Jim Nelson found when when he did that titration”

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Hormone balance 1:52:02 0
“if you give 17 alrol to male mice it pushes their lifespan Way Beyond females it's not merely mimicking the good stuff if there is good stuff that estrogen 17 beta does in females if so it wouldn't go fur than seven females are and it goes well beyond significantly Beyond normal females or drug treated females because the drug doesn't affect female longevity at all what it binds to in which cells in which tissues what it's turning on biochemically is at this point quite obscure”

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Hormone balance 1:56:17 0
“the conversion from estradiol to estriol dependent upon testosterone or some other testicular hormone”

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Hormone balance 1:56:52 0
“the hydroxy version of estriol is great for males, it's actually at least as good as 17 alestra Dial”

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Hormone balance 1:57:14 0
“it is the first drug we found that diminishes lives sped females”

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Substances 2:02:18 0
“the evidence that it works is very bad it it almost certainly doesn't do anything at least in mice in terms of Aging”

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Substances 2:04:02 0
“we tested it and it didn't didn't work um that is it didn't extend Mouse lifespan”

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Substances 2:06:16 0
“the fact that something fails mice doesn't mean it's going to fail in people”

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Substances 2:10:06 0
“one of the drugs that people used to take care of their seasickness was an over-the-counter drug called Meine.”

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Substances 2:12:04 0
“Meine was suggested to us by Gino Copasi. He knew that Rapa was good as an anti-aging drug and it was a TOR inhibitor so he took several thousand FDA approved drugs and in a tissue culture assay he said which of these inhibit TOR maybe a safe drug that inhibits TOR could find a place as an anti-aging remedy and at the top of his list to everyone's surprise certainly his was Meine.”

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Substances 2:12:24 0
“it does indeed lead to at the dose we used a significant increase about 10% in a lifespan of the male mice. It did not affect females so we're going to try it again at higher concentrations and see if we can get that to go.”

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Substances 1:34:53 0
“it is the first time we've gotten winners that you can buy without a prescription over the counter they're not as strong in terms of lifespan benefit as the four drugs we were talking about earlier on in our discussion but um uh and of course we don't know if they will work in humans at all”

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Substances 2:16:09 0
“we've tested ftin um this was suggested to us by poor Robbins and Jim Kirkland and tamaron and their colleagues um if I see is undergoing a lot of human trials because of claims that it is a senolytic drug”

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Substances 2:16:58 0
“we gave fetin uh two different dose regimes suggested by Dr Kirkland he had found in his lab with his kind of mice that they did work at this dose so that was good news we thought we were trying to replicate his stuff in our mice at much larger scale”

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Disease prevention 2:21:23 0
“I believe that there certainly are cells that accumulate in mice and in people when you get old that do stuff that's bad for you. Some of them might make this set of cytokines, some of them maybe they can't divide anymore and that's bad for you.”

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Disease prevention 2:23:41 0
“Judy cesy was the key author... she measured the number of senescent cells... and proved that it went up a lot with age.”

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Disease prevention 2:23:59 0
“The actual cell counting was done by Monica Peacock... the skin section that had the highest number of beta-gal positive cells had only one positive cell per 10,000.”

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Cognitive stimulation 1:47:35 0
“I'd love to know whether these drugs slow cognitive failure of course.”

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Cognitive stimulation 1:47:40 0
“the addition of your colleague now coming on board for all tier 2 studies to to have a cognitive component I think is incredibly exciting.”

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Most important takeaways of the video

  1. Evidence supports the effectiveness of mutants and diets like calor restriction and methionine restriction, along with ongoing research on drugs like rapamycin for anti-aging effects.
  2. The goal is to discover drugs that can decelerate the aging process and increase lifespan in mice, with a focus on translating these findings to human aging interventions.
  3. Capap Pro, an FDA-approved drug for blood pressure, was found to slightly increase lifespan in mice, surprising researchers.
  4. Genetic research in mice has identified specific genes linked to lifespan, with gender-specific and age-specific genetic markers contributing to understanding genetic influences on aging.
  5. Laboratory mice used in research are genetically identical and homozygous, a level of genetic similarity not found in natural human populations, which can

Overview of Anti-Aging Research and Substance Effects

Anti-Aging Interventions

The quest for anti-aging solutions has led to the discovery of three key mutants and effective dietary restrictions, including caloric and methionine restriction diets. Emerging drugs like rapamycin show promise in delaying aging processes. Further, surprising findings reveal drugs like Capap Pro, initially approved for blood pressure, modestly increase the lifespan in mice.

Genetic and Substance Insights

Genetic studies have pinpointed specific genes linked to lifespan, revealing both gender-specific and broader effects. This includes the identification of lifespan-extending genetic mutations and the use of genetically homogeneous mice to minimize variable influences in studies.

Drug Delivery Improvements

The pharmaceutical approach includes improving rapamycin’s delivery via encapsulation to bypass stomach degradation, enhancing its effectiveness. Research also notes substantial sex-based differences in drug metabolism, indicating the necessity for tailored drug dosages.

Dietary and Environmental Factors

Unexpected environmental factors, such as site-specific conditions, have been noted to influence mouse lifespan studies, suggesting complex interactions between genetics, drugs, and environmental conditions. Moreover, difficulties in measuring actual food intake in mice complicate nutrition-based research.

Exercise and Health Monitoring

Investigations into exercise emphasize its profound effects on metabolic health, including increased levels of certain proteins linked to decreased aging signs. These studies pave the way for potential pharmaceutical mimics of exercise benefits, such as enhancing cognitive functions and overall physical health.

Challenges and Future Directions

Despite promising advances, translating these findings from mice to human treatments remains challenging. The variable effects of substances like Resveratrol and Nicotinamide Riboside, which show minimal impact in mice, underscore the complex biology of aging and the potential disparities in treatment outcomes between different organisms. Nonetheless, ongoing research continues to explore these avenues, aiming to extend not only lifespan but also healthspan in humans.