Reversing Biological Age: Have we finally found the answer?

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Reversing Biological Age: Have we finally found the answer? | 30 - LTW #5

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The Optispan Podcast with Matt Kaeberlein

Күн бұрын

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@espinosalexis 3 ай бұрын

I see Horvath is first author! You can also interview him about this paper and all his reasearch in other areas of aging and biological clocks.

@Jessica-kk1cz 2 ай бұрын

MK would much rather go after the guy in his 80s with mild cognitive issues, than the Nobel Laureate who can hold his own. MK misses the point - or is in denial. Clearly regardless of whether it’s reversal or not, that lifespan for the rat is impressive, and its progress once the pathway is identified and is repeatable in humans. It’s among the several approaches that shows significant promise - and a lot more so than MK’s die hard dedication to rapamyacin implies that drug deserves

@squamish4244 2 ай бұрын

@@Jessica-kk1cz He is rock-hard for rapamycin, which just has too many side effects.

@abrahamnorthhampton3327 3 ай бұрын

A discussion between you and Dr. Katcher, moderated by Richard from @ModernHealthspan, would be terrific

@optispan 3 ай бұрын

Agree, we invite Dr. Katcher to come on the podcast any time! - Tara

@joshlocher71 3 ай бұрын

@@optispan hi matt my name is josh and i heard about david sinclair's cocktail hopefully it really is a success

@beardumaw24 3 ай бұрын

Thank you for keeping things real and honest ! Much appreciated 👍

@catorepublic 3 ай бұрын

Thank you for this informative review of E5. I hope Dr. Katcher does an interview with you. I also hope he publishes more detail on his formula so that his work can be replicated and the exact factors can be determined.

@NickWestgate 3 ай бұрын

Well, a patent was filed, but it's hard to read. Other groups have since published that ESVs (and RNA) seem to be the main active component, and Katcher has confirmed that this was his hypothesis.

@user-ln3vw5mo7n 3 ай бұрын

It's "exosomes' not "episomes' - Your calculations are wrong, but I won't argue, again "Time will tell" - also I'm no longer with Yuvan, I've formed a new corporation; LXR-VT Corp.

@jimroth7927 3 ай бұрын

Hi Dr. Katcher. Hope you are well. Please do the occasional interview, so we know how things are going for you. Best wishes.

@alexandrejuve1305 3 ай бұрын

Hope you have better luck with this new partners. We will love to see you replaying to Matt’s arguments, I hear many weak points that you can refute

@squamish4244 3 ай бұрын

Get results in dogs, and we will be impressed. I'm sick of all the mouse and rat studies. I wish you the best.

@askingwhy123 3 ай бұрын

Another great discussion that explains the issues and dispells the hype.

@jamesgilmore8192 3 ай бұрын

Matt -- Appreciate your comments on reversal of aging. My working definition on mice to claim reversal would be to have an intervention on one group, and then run that group and a control group in the standard way. Then measure everything possible about the aging process in both groups, and if you can show they are equivalent, except the group with the intervention just transposed in time (and living longer), then you have evidence for reversal of aging through a statistical equivalence test. Kaplan-Meier and some clocks isn't enough to claim reversal, those are just specific markers. What I suspect is that most interventions won't reverse overall aging in an equivalence time transposed way, but rather will target specific mechanisms of aging, and if you look hard enough you'll find differences in the way the mice groups age for example. There needs to be a wider discussion of what differences/markers constitute evidence for reversal.

@tombenson5957 3 ай бұрын

What a wonderful deep dive into Parabiosis - all of the many flavors, theories, and counter-theories. I listened to it twice. Thank you Dr. Kaeberlein.

@espinosalexis 3 ай бұрын

Not a mention at all during the episode about the first author: Steve Horvath. (One of the most cited authors in the longevity research!)It is now clear that you do not want to mention anything about him or his work. This is unfortunate, as more and more people every day are looking into his research and using his biological clocks. Same for Glycanage. I believe you should be open to discuss usefulness of these clocks! Has Rapamycin shown any reversal of these clocks?

@HvdHaghen 3 ай бұрын

In his interviews Harold Katcher gave an explanation why Sima was an outlier. The treatment was repeated after a certain time.

@steveholmes1736 3 ай бұрын

As a citizen, scientist, I find this Content very interesting! I have subscribed. Thanks,

@jimroth7927 3 ай бұрын

If two things are not different then they are the same. If the goal of anti-aging research is to "live long and prosper", as any self-respecting Vulcan knows, and if a given treatment improves general health and extends maximum lifespan then it seems reasonable to call that treatment "anti-aging", even if not all aspects of aging are affected. Does an anti-histamine have to eliminate 100% of histamine in order to deserve it's name?

@zisoskatsiapis656 3 ай бұрын

The study in Argentina was funded by the same organization that funded Yuvan, but definitely not related to E5. In Argentina study, plasma from young rats was injected to old rats. If you read the paper, it was very obvious. The effects were positive, but did not come close to those of E5

@jimroth7927 3 ай бұрын

Seems like Matt did not come across the pre-print papers that detailed the early rat experiments. Those papers seem noteworthy to me. I am not an aging expert, I am a layman, but I am an aging layman! I thought the preprint papers interesting, because they examined many health parameters, more than Matt mentions, and they showed that old rats, when treated, gradually improved, until their health parameters were similar to the young rats. I am guessing that caloric restriction would not be effective if started in old rats, so that seems like an important difference between E5 and caloric restriction.

@mkaeberlein 3 ай бұрын

Based on group sizes, it appears that the data from several of the preprints were combined into this single peer-reviewed paper, although hard to tell given the limited methodology provided. We'll try to go through the pre-prints in depth and provide an update. Re: caloric restriction, the mouse data is mixed, but there are studies showing lifespan and healthspan benefits when started in middle age. More convincingly, we already know it has this effect in people. Take middle-aged obese, sedentary people and put them on caloric restriction and a whole bunch of biomarkers improve. This is sort of my point. I think E5 and caloric restriction and exercise and rapamycin all improve health and reverse a subset of biological age parameters. Do any of them fundamentally "reverse biological aging"? That hasn't been shown and I am fairly certain that there are aspects of biological aging that none of them reverse. - MK

@SilverFan21k 3 ай бұрын

A worthy topic

@robertdaymouse3784 3 ай бұрын

I will take an interest in E5 when Harold Katcher starts looking younger than 80.

@smedleyjefferson1450 3 ай бұрын

That may be too much to ask: There were rumors that Henry Kissinger was taking the blood of young animals for a decade or so, which might explain why he made it to a 100, even though he was fat and looked very old.

@HvdHaghen 3 ай бұрын

Harold Katcher did an experiment on the skin of one hand. That looked younger.

@Montie-Adkins 3 ай бұрын

I mean, a Katcher interview is a little rough. His age shows during interviews on long, slow, meandering answers. In short, this may be a great thing to make one really healthy, and as a result you get extra time. A bridge to make it to the next bridge.

@squamish4244 3 ай бұрын

That's exactly my thought as well. Blood factors may not be the key to immortality, but they could drastically increase healthspan and extend all of our lives out to the 100 years that even Dr. Kaeberlein says is his belief, and so does Peter Attia and other longevity doctors. Well, good lord, that is HUGE if it is possible. It would transform society, by itself, if 100 healthy years and a short drop-off at the end was the norm instead of the demographic catastrophe-in-waiting that we have now. The projections for 2050 for Alzheimer's and dementia are terrifying. My parents insist that _they_ will not get these diseases, but really, everyone who has ever fallen victim to neurodegenerative disorders has thought the exact same thing. Including my grandmother, a survivor of a world war and the early death of her husband and never one to mince words, who said in her 80s, "If there was a pill for youth I'd take it!" Not to mention our insane life cycle, which is a mad race to cram in an education, travel, finding a career, a mate, securing your finances, and then having kids before you are too old and tired to want to do that anymore, if it is even biologically possible. What if you suddenly had ten extra years to do all of that? Holy crap! And blood factors seems the most immediately accessible of all the work that's being done. If it works on dogs, the odds that it will work on people go WAY up. At least a lot of companies are doing work on this now, not just Yuvan, which can't seem to organize its way our of a paper bag. I hope Harold Katcher can get it - and he has volunteered to be the first human patient - before he dies.

@SilverFan21k 3 ай бұрын

Congrats on 5k subs

@jimroth7927 3 ай бұрын

I don't think there is a mathematically valid statistical principle that simply says "throw out outliers". Some measuring devices produce lots of small errors and a few big errors. For that type of expected measurement error, it is probably reasonable to throw out extreme outliers to restore a normal error distribution and allow least squares analysis to be used. But the long lifespan of one rat in Dr. Katcher's experiment is probably not the result of measurement error, so the assertion that statistical best practice demands it be excluded from the results is wrong.

@bob-ss4wx 3 ай бұрын

Glad to see Matt critique study as a scientist

@bw4611 3 ай бұрын

All excellent points Matt. And I’d love for the next E5 experiment to show us an old rat living double its normal age (or just significantly longer than existing, known methods). Personally, like you, I’m hoping it can.

@andrewm6340 3 ай бұрын

Hi Matt! Andrew Moore here, remember, from BioEssays days; now freelance. Very nice analytical dissection of the work and the paper! Question: the immune system seems to play an important role in ageing (see thymus regeneration experiments). Why would one expect to be able to equate heterochronic parabiotic models with heterochronic plasma exchange models, given that in plasma exchange there are no immune cells being transfered, albeit definitely antibodies and cytokines. Any idea what's going on there, and what the involvement of the immune system in ageing is in terms of circulating factors? Best wishes, Andrew

@hodosmb 3 ай бұрын

have long been waiting on a review of e5. lot's of hype about Dr. Katcher's work and not much commentary by real scientists

@ryanm9565 2 ай бұрын

I'm about to extract E5 myself and test it topically first.

@veredk4384 3 ай бұрын

I was wondering about E5 ever since I watched an online presentation/interview with dr Katcher...You bring up a few good points (It's still very intriguing!). I just wanted to mention that while extreme caloric restriction does probably work, it's a very tough intervention for the "general public" to follow, to say the least, 😂! So comparing alternative methods for improving health span to CR is not so fair. I keep seeing all sorts of "discoveries", like rare sugars in Avocado as an exercise mimetic that worked "wonders" in obese people, compared with controls - who were "normal", average, aged matched humans...you might expect the suggested intervention to be 'eat less/move more', not an EM...Alas, human nature needs to be taken into account 😉 Love your show!

@optispan 3 ай бұрын

Agree that caloric restriction suffers from adherence issues. We need better interventions. -Tara

@zisoskatsiapis656 3 ай бұрын

Fully agree that comparison is definitely not appropriate. CR needs to start at very young age, and will result in miserable life. Just not possible. On the other hand, even if E5 is partially effective, it will be relatively easy to take advantage of.

@anilkumardhar 3 ай бұрын

Awesome..!!

@bertimus7031 3 ай бұрын

Dr Katcher was simply protecting his IP, so he could get an commercial advantage. He has every right to do so. I think he the only reason he disclosed the exosomes is because other scientists had caught on. He did not in any way commit bad science. You are Very opinionated.

@adjusted-bunny 3 ай бұрын

Interesting. I will search for piglets tomorrow. I hope they will be cooperative.

@szghasem 3 ай бұрын

Thank you Dr. Kaeberlein for holding their feet to the fire. Your presentation was very informative. I've heard rumors about a significant market for the plasma of young individuals. I'm curious about its effectiveness.

@ryan_the_red_4907 3 ай бұрын

Good topic again, really keeping it interesting 🙌

@brentvan488 3 ай бұрын

Pacific Salmon are young and healthy as they swim up the river to spawn, then they spawn and two weeks later they are dead. Atlantic salmon don't immediately die after spawning. I think that sort of rules out the wear and tear theory of lifespan for Pacific Salmon at least.

@mkaeberlein 3 ай бұрын

Sure, rare examples of programmed senescence in animals exist like Pacific Salmon. It doesn't rule out the idea that Pacific Salmon are still accumulating damage due to wear and tear however. Simply that it's not that specific damage that kills them. People who walk in front of buses on the freeway are not dying due to "wear and tear". Those folks still experience the same biochemical processes that drive biological aging, it's just that something else (a bus going 70 mph in this case) that kills them before the wear and tear does. - MK

@zisoskatsiapis656 3 ай бұрын

@@mkaeberlein As I understand, Dr. Katcher does not claim that there is no damage due to various processes or environmental factors. What he claims is that when the animal is young, it can repair these damages. Therefore, if age is reversed, and all damages can be repaired, all these damages are not important.

@zakmatew 3 ай бұрын

I agree completely! Age reversal is not equivalent to health improvement. When you see an old biological organism becoming young, then that is age reversal. So far there has been only one case from the University of Alabama, where the integumentary system's age in a mouse model was completely reversed but...No one has reproduced it yet.

@HarryJensen-kr4qz 3 ай бұрын

Yeah, that would be E5. Yeah, although maybe unpublished it's been around for a while. They used pigs but I think it can come from any mammal.

@HvdHaghen 3 ай бұрын

What about eggs?

@georgbrindlinger1008 3 ай бұрын

Fascinating, thanks a lot!

@TheSocialSmilingMonkey 2 ай бұрын

Simply put No the mechanisms involved in ageing may be more comprehended, however life cycles are life cycles .

@paulcohen6727 3 ай бұрын

Some varieties of experimental animals benefit from calorie restriction while others don't. The ones that do benefit, probably do so because restricted eating compensates for genetic deficiencies such as those that help the body cope with excess fat or cholesterol or other dietary problems. So, since this seems to be the case, a healthy low fat, low cholesterol diet and exercise along with good sleep quality and all the other habits we already know about may well increase lifespan beyond restricted calories of the speculative E5 treatment.

@natureins4644 3 ай бұрын

Clearly old blood has a detrimental effect on young animals. Hence, out of curiosity, has anybody tried filtering a blood in older mice starting with something like hemodialysis to see if it has a positive impact on the healthspan and or lifespan?

@saliksayyar9793 3 ай бұрын

Were experiments done in India? Each large cohort of rodents have an outlier or more. Need data as Kaplan-Meir graphs with controls and show power stats to detect differences. The SD rats you ate showing the median survival. Katcher is not showing such data

@cactuscanine3531 3 ай бұрын

The more I listen to Matt K., the less I like him. Rather dismissive of other’s ideas and work.

@sergey9986 3 ай бұрын

Conboy - what an unlucky surname for a scientist.

@jimroth7927 3 ай бұрын

One of my grandfathers was named Conrad and he had a used car lot that he called "Con's Auto Sales". I never saw any actual sales happening when my dad would take me to visit, just old guys sitting in the office and shooting the bull. However, Conrad always gave me a quarter when we visited and, in those days, that was serious money for a little kid.

@philipbeauford 3 ай бұрын

When using big “impressive” sounding words like parabiosys or heterochronic.. plus the constant focus on needing “peer review”.. otherwise the info is ignored.. this guy is right away missing the overall point and is not helping anyone in the end. I can’t stand elitism, I can’t stand jargon, if you want to actually help people, learn how to communicate EFFECTIVELY & EFFICIENTLY.. big words are an immediate sign to me that this person is definitely NOT someone who will be making any big strides in longevity.. or any field really.. probably ever. People that have a great ability to effectively communicate without using big impressive sounding words are always your best bet.. why?.. bc first that is the most effective communication to the largest number of people. Anyone can understand analogies if they’re good enough. Sitting on your self made pedestal, monotonously spouting big word after big word, citing study after study is NOT moving any needle forward. Debate, debate, debate that’s all pessimistic skeptics do in the end. Do something actionable, take action in some way, learn to communicate to any average individual , which btw takes more intelligence than using only big words over and over..

@brett7077 3 ай бұрын

🗑️ analysis; look into epigenetic clocks

@treewx 3 ай бұрын

is it real? probably not.. could it one day be real.. maybe. But I reckno reversal.. is kinda misleading. . easy to argue of definitions.. maybe a "proxy reset" might be as good as we get and maybe that's good enough. I dunno... i am going strong at 120 and someone says.. hey that's not age reversal.. I'll be like fine.. I just want my body in a state where I can keep going..