Unlocking Longevity: Advances in Aging Research, Prevention, and Healthspan

Nutrition 5:34 0
“not being insulin”

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Disease prevention 5:07 0
“all of the drugs at least that extend lifespan in mice and could potentially do so in people do so by postponing diseases both the diseases that will kill you that's why they extend lifespan and the diseases that won't kill you but which will annoy you and make you very unhappy to be old”

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Exercise 5:34 0
“which is true by the way of non-molecular tools as well that's true exercise”

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Genetics 6:42 0
“if you go back to Cynthia kenyon's work which may have been the thin end of the wedge into the idea that lifespan was malleable albeit through a genetic manipulation in a less relevant model”

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Disease prevention 9:55 0
“we're getting better and better and better at treating heart disease and cancer and all these things and keeping people alive when they wouldn't have been alive 10 years ago”

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Purpose 9:11 0
“making an argument that that's a good idea to people who actually have the resources to carry it out as a has not so far been enormously successful unfortunately”

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Disease prevention 11:33 0
“when you look at maternal and infant mortality were horrible when you look at gun violence and suicide and homicide were horrible and most of all when you look at overdoses were horrible”

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Disease prevention 11:55 0
“once an American reaches the age of about 65, all of a sudden they jump to the top of the list.”

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Disease prevention 13:01 0
“60% of Americans have at least one chronic disease and the median age in the United States is 38 point something.”

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Mental health 17:14 0
“you never pay attention to the mental health piece at least the biologist don't right”

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Purpose 17:29 0
“we say to every one of our patients um and I write about this a lot in the book right everyone will have a marginal decade which I Define as the last decade of your life so obviously by definition everyone has a marginal decade most people do not realize the day they enter it but most people have a pretty good sense when they're in it right okay so the exercise we do is we go through with the patient and we say what are the things that are most important to you to be able to do in your marginal decade”

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Cognitive stimulation 18:42 0
“on the cognitive side you have people who say I want to be able to run my hedge fund and still make money and make really important investment decisions and other people are like I want to be able to do crossword puzzles and read the newspaper and that's my standard”

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Disease prevention 29:11 0
“we have drugs now anti-aging drugs in mice and they extend Mouse lifespan and they do it mostly by postponing cancer because most of our mice die of cancer and if you look at age adjusted cancer incidence rates our drugs reduce these by a factor of 10.”

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Disease prevention 30:20 0
“I think this is because we're we think about health all wrong we think let's wait till get cancer and see what we can do about it that's what cancer biologists do you have cancer okay how can we better treat that or could we have diagnosed it earlier what rich is saying and what we can know how to do in lots of model organs it prevents you from getting cancer delay it for a considerable amount of time.”

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Disease prevention 33:54 0
“one of the bad things about aging is it's a risk factor for many diseases”

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Disease prevention 34:01 0
“aging is a risk factor for disease and so saying that aging is a disease confuses that discussion.”

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Disease prevention 35:22 0
“we have to call aging a disease in order for FDA to approve a drug for aging”

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Genetics 35:59 0
“I don't believe there is such a thing as biological age. I think there is potentially an age of your heart, an age of your liver, an age of your lungs, an age of your brain.”

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Genetics 40:11 0
“we also know now there are single genes that significantly modulate what I would call the rate of Aging”

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Genetics 40:28 0
“animals Across The evolutionary Spectrum seem to age at different rates by modulating single genes”

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Metabolic health 41:08 0
“I know your V2 Max, I know your zone two, I know your muscle mass, I know your visceral fat”

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Genetics 42:38 0
“I tested four different direct to Consumer biological age kits they were all epigenetic biological age tests”

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Genetics 45:25 0
“is this number predictive of future years of life because right now we have this thing called chronologic age that is the single best predictor of future years of life so do we think biologic age as determined by these tests is better as a predictor of future years of life which by the way would be very testable”

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Genetics 46:12 0
“you can tell if you have a your 40-year-old patient and he or she is fat doesn't exercise eats mostly cheeseburgers you know that their life expectancy is probably not as good as the 40y old patient in your your next waiting room that has extremely healthful habits and whose parents live to be 100”

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Genetics 50:37 0
“I am hopeful that um epigenetic algorithms can get to the point where they can replace many certainly not all but many of the other biomarkers that are being measured”

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Genetics 51:12 0
“if we had a mechanistic connection to the specific methylation changes and some cause of Aging or age related disease in other words this change in methylation changes this particular Gene's expression level which changes the rate of biological aging”

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Genetics 51:50 0
“do we believe that the epigenetic changes that we observe over time which are undeniable are causal in the arrival of other states everything from the arrival of senescent cells the increase in inflammation the reduced function of the organs which really is the Hallmark of aging”

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Genetics 52:18 0
“reversing the epigenetic phenotype will undo the phenotype of interest”

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Inflammation 57:12 0
“I imagine inflammation is on one or more of these... chronic inflammation... this particular set of cytokines might be overexpressed by some glial cells and that leads to loss of cognitive function whereas this other overlapping set of cytokines produced by the macrophages in your fat may lead you more prone to diabetes or metabolic syndrome.”

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Disease prevention 57:50 0
“This particular set of lymphocytes are necessary to repel COVID and that's why you are more susceptible to COVID.”

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Disease prevention 1:03:29 0
“diabetes is you can formulate these questions because a lot is known about type one diabetes and I understand 05% of the biology of is is I was giving you're off by an order of magnitude who's raising You by a I thought your One log off so so it formulating the questions in exactly the way Steve did makes it clear how difficult it is to evaluate the concept that epigenetic change contributes to pathogen gen is in type 1 diabetes and we know more or less what is going on in type we don't know what's going on in aging we don't even know what part of the body it's going on or parts more likely of the body”

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Disease prevention 1:04:52 0
“people are using you know partial or transient epigenetic reprogramming and asking can that have effects on biological aging I'm actually cautiously optimistic it can I don't think it's going to be a GameChanger but I think you can modulate aspects of biological aging”

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Disease prevention 1:05:56 0
“if we could get to the point where we could locally deliver vectors that would epigenetically change condra sites so that you could take osteoarthritis in the knee and just regenerate cartilage regenerate cartilage regenerate useful by changing the EPO but is that biological aging right I wouldn't be convinced that's modulating the biological aging process”

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Disease prevention 1:09:57 0
“rapamycin can be unsuccessful as a chemotherapeutic agent and can yet be very successful as a cancer preventive agent”

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Disease prevention 1:14:38 0
“the only thing we've got going for us right now is prevention right we don't have too many silver bullets in the treatment gun despite massive spending”

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Disease prevention 1:15:21 0
“it's going to be much more efficient and effective to keep people from getting it in the first place”

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Disease prevention 1:16:09 0
“if we defeat Alzheimer's disease it's going to be because of the biology of Aging it's not going to be because of the drugs that get rid of”

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Disease prevention 1:16:45 0
“a lot of kidney disease all of those things can be improved dramatically by targeting the biology of Aging”

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Disease prevention 1:20 0
“we have this one study using everus that show that gives us a hint that says hey this might actually enhance immune function in people in their mid-60s but we need the follow-up study”

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Disease prevention 1:04 0
“testing anti-aging drugs in people is a whole separate set of tangle of difficulties”

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Disease prevention 1:39 0
“there are over 80 cytic studies in early clinical anti-aging drugs”

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Disease prevention 4:24 0
“biomarkers change so rapidly and we know the relationship between the biomarker and the disease state”

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Genetics 1:26:35 0
“we've looked now at five different single gene mutations and this whole set of 12 or roughly 12 aging rate indicators always changes in every slow aging Mouse”

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Disease prevention 1:26:59 0
“if you want to know whether metformin or Kagen or something slows Aging in people and you don't want to wait 20 years but you've got things that tell you whether they're in a slow aging State how fast they are aging versus normal”

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Body weight 1:29:43 0
“you find someone who is overweight diabetic and smokes and has hypertension you get hundreds of these folks you put half of them on a sort of to be ethical a plan where you try to get them to stop”

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Disease prevention 1:33:07 0
“the difference is probably Amplified in disease specific cases like heart disease cancer and Alzheimer's disease probably less relevant when you're talking about aging because even a flawed Mouse model still ages in fact it's designed to age in a certain way”

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Disease prevention 1:33:46 0
“most things that do have an important effect in mice fail in human clinical trials and it's for a variety of reasons sometimes humans are different from mice sometimes the drug has side effects that are tolerable in mice not tolerable in people”

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Disease prevention 1:35:45 0
“I went to the FDA to try to get them to approve a trial of metformin and we didn't couch it in aging cuz you're right as soon as you mention aging their eyes glaze over and they're not interested anymore but we did it in terms of multimorbidity and they were fine with that”

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Genetics 1:37:23 0
“you might miss the signal if you found a a proteomic genomic epig like if you found a multimodal signal that detected a rate of detection a difference in rate of Aging between those two very extreme sets you might miss it with a geroprotective drug which wouldn't be as dramatic as that change”

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Genetics 1:37:43 0
“there are people who claim there there are epigenetic signatures that do that that that correlate quite well they claim with health outcome 10year mortality 5year mortality threeyear mortality in people and um are measuring the rate of biological aging because it's out there”

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Exercise 1:39:15 0
“you took a lot of people and gave them intense uh exercises and dietary changes to improve their health out likely Health outcomes and that's a good good place to start a discussion”

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Exercise 1:43:14 0
“the effect of exercise on longevity is pretty small its effect on quality of life is enormous”

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Exercise 1:44:13 0
“exercise increases an enzyme called gd1 in the blood of exercise people and in mice and sv's lab has shown that if you elevate gld1 it does great things to your brain more neurogenesis and more brain derived protective factors”

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Exercise 1:45:05 0
“anti-aging drugs the Cal restricted diet the isoline restricted diet and five different single Gene mutants that extend L Bane and mice they all Elevate gld1”

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Disease prevention 1:49:30 0
“where it's most talked about is in dementia prevention right now”

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Metabolic health 1:49:17 0
“in an individual who is metabolically healthy but overweight”

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Body weight 1:51:56 0
“do they also lose 15% of their body weight”

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Disease prevention 1:56:58 0
“The notion that aging is due to senescent cell accumulation is bad for two reasons: it's a grotesque oversimplification and the evidence for this is awful.”

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Disease prevention 1:58:25 0
“The last point I'll mention in this rant has to do with senolytic drugs. The ITP was asked to test an allegedly senolytic drug called fisetin. It had no beneficial effect whatsoever.”

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Disease prevention 2:00:50 0
“I think there's strong evidence that getting rid of these p16 positive cells which is really what it's all based on can have an improvement in health and in longevity.”

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Disease prevention 2:02:01 0
“we tried seven times to show depletion of sessen cells by in their mice using their drug and and went zero for seven.”

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Disease prevention 2:02:29 0
“when we undid the code there was no effect on sess and cells whatsoever.”

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Metabolic health 2:12:14 0
“Rich, do you think metformin is geroprotective in humans? I know it's yeah doesn't appear to be in your mice.”

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Metabolic health 2:12:32 0
“Diabetics on Metformin had lower survival, lower mortality risks.”

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Metabolic health 2:13:47 0
“Metformin is safe over the long term in people but I don't think there's much evidence that it's anti-aging.”

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Metabolic health 2:13:59 0
“The observational evidence, ignoring the Banister paper, just the observational consistency of the data that it reduces dementia, cancer, cardiovascular disease suggest to me there's enough smoke there to look to see if there's fire.”

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Disease prevention 1:39:52 0
“George Martin who died a couple of years ago once went through and cataloged all the human diseases he could and tried to look at the similarities of their phenotypic changes relative to what happens with normal aging he came up with diabetes as having the most similarities to accelerated aging of any of the groups that he looked at.”

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Metabolic health 2:21:51 0
“we've demonstrated that it reduces all cause mortality in your mice in males in males do you believe and we know exactly what kagaoan does in the kidney and we know that those mice live longer do you believe that the longevity benefit came through glycemic control because there was no difference in weight if I recall.”

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Disease prevention 2:24:06 0
“we said one year healthy aging $ 38 trillion that's you know that makes you know that should talk to Congress and nothing else does”

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Disease prevention 2:24:34 0
“it's quite possible that the trial will be successful even if metformin is not a effective gerotherapeutic”

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Substances 2:25:20 0
“because inhibiting mtor increases lifespan and slows aging”

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Disease prevention 2:30:07 0
“Linda Partridge just published in bioarchive at least a nice paper Rapa mice and increased lifespan for mice if she added an inhibitor of a different kise called irk it did better it did the inhibition by irk work by itself but it actually improved on rapy.”

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Disease prevention 2:30:29 0
“the KK kinas inhibitor is working in an entirely different pathway it's affecting the proteome by increasing the uh uh degradation uh through a Chevron mediate autophagy mechanism which is not affected by rapy.”

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Disease prevention 2:31:25 0
“there are drugs out there that hit both types of kineses right there are drugs out there that are that are ATP competitive Inhibitors that have different affinities for different types of kinases haven't been tested for longevity these dual kinas Inhibitors right.”

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Disease prevention 2:32:06 0
“most people using ramyon off label for potential Health span effects most doctors prescribing it are recommending once weekly dosing you know in the 3 to six sometimes 8 10 milligram range.”

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Substances 2:36:57 0
“I'm not 100% convinced that there are no health benefits from Resveratrol. I'm pretty convinced it there's no reason to believe it affects the biology of Aging or is a longevity drug but I can't say for sure that nobody would ever benefit from any dose of ratol.”

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Substances 2:39:44 0
“I think NAD is is very very interesting molecule and I don't think we could throw out you know manipulating NAD as something that could be important for aging. I just think the evidence is there at this point.”

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Substances 2:40:35 0
“The data is decidedly mixed both in the literature uh pre-clinical literature and in people as to whether or not boosting NAD increases lifespan improves Health span.”

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Substances 2:42:15 0
“I don't personally believe there is enough evidence to think that NAD precursors as are being marketed today are likely to benefit most people.”

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Substances 2:42:37 0
“There's at least one study in mice that giving NMN to aged mice causes kidney inflammation and potentially kidney pathology.”

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Disease prevention 2:48:47 0
“if it works great that's a win too”

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Disease prevention 2:49:57 0
“we still wouldn't be using anesthesia if we had to wait figured out how it worked”

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Disease prevention 2:51:43 0
“there's at least evidence to support that idea”

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Overview of Disease Prevention and Aging Research

The evolution of aging research and disease prevention is marked by significant insights into how diseases like cancer and heart disease are treated and managed, reflecting better survival rates over the past decade. Notable discussions involve the extension of lifespan in mice through drugs that delay diseases, suggesting possible implications for human healthspan. Additionally, the average life expectancy notably improves once Americans reach the age of 65, illustrating effective chronic disease management in older age groups.

Genetic Factors in Aging

Research continues to show that certain genes can considerably influence the aging process, suggesting that genetic manipulation might adjust how quickly organisms age. Epigenetic markers, particularly through methylation, have been studied for their potential roles in aging, addressing the malleability of lifespan through genetic factors. Conversations around the biological variance in aging rates across different species further highlight the influence of genetics. Despite these advances, the practical application of these findings in human aging remains tentative and speculative.

Metabolic Health and Longevity

Markers of metabolic health such as V2 Max, muscle mass, and visceral fat play crucial roles in assessing overall health and potential longevity. Drugs like Metformin, historically used for diabetes, are discussed for their geroprotective potential, although the evidence linking them directly to anti-aging benefits is mixed. The dialogue extends to other interventions like Caloric Restriction and drugs impacting the mTOR pathway, hinting at broader applicability in longevity research but with cautious optimism regarding their direct implications for humans.

Challenges and Ethical Considerations in Aging Research

The translation of successful results from mice models to human trials presents significant challenges due to physiological and tolerance differences between species. Ethically, the focus has shifted more towards prevention strategies, particularly in the context of neurodegenerative diseases like Alzheimer’s, where current treatments are inadequate despite substantial funding.

Role of Exercise in Health Management

Exercise is repeatedly emphasized as a critical non-pharmaceutical intervention that, while having a minor impact on longevity, significantly enhances life quality. It impacts various biological pathways associated with aging and chronic disease management. Notably, discussions point towards physiological benefits such as increased levels of certain enzymes linked to neurogenesis and brain health.

Supplement Use in Longevity

While supplements like resveratrol and NAD precursors are widely marketed, their actual benefits in terms of aging biology and longevity remain inconclusive and controversial. The lack of robust evidence leads to skepticism about their efficacy in extending lifespan or significantly impacting age-related health outcomes.

Future Directions and Economic Implications

The economic implications of aging research are substantial, potentially influencing future healthcare policies and research funding directions. As discussions advance, the integration of findings from genetic studies, pharmaceutical and non-pharmaceutical interventions, and broader public health initiatives will be critical in shaping approaches to aging and chronic disease management globally.