Aging reversed? Testing the information theory of aging.
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- Опубликовано: 31 июл 2024
- Aging. It’s what we do. And what i’m here to talk about today. In particular, addressing a recent paper that claims to test the information theory of aging that has come out from David Sinclair’s lab at Harvard Medical School and claims to drive aging both forwards and backwards.
In this paper they generate a mouse model (ICE-mice) where additional DNA damage can be controlled to induce, they hope, epigenetic changes to test their theory that loss of epigenetic information drives aging. Let's find out.
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TIMESTAMPS
Intro - 00:00
Information theory of aging - 00:45
The results - 05:00
The thoughts - 10:45
References:
Loss of epigenetic information as a cause of mammalian aging - doi.org/10.1016/j.cell.2022.1...
www.science.org/content/artic...
Please note that The Sheekey Science Show is distinct from Eleanor Sheekey's teaching and research roles at the University of Cambridge. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed.
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i deliberately did not present a lot of their data. it was hard for me to pick what i thought were the best figures for providing a good overview without showing too many figures that show things are still quite inconclusive and would take much time for me to explain what they are showing. i presented how i interpreted the data. Happy to hear other thoughts :)
Please check your FB messages!
DOES THAT MEAN THAT TAMOXIfen accelerate aging?
I think there's probably a way to marry this with more classical theories.
I can attest to some age reversal. I started taking nr when 67. 74 now. I have many instances of both reversal and arrest. I seem to have stopped aging. Lifting weights again. Thinking better and faster. And many other examples. What is curious is my tinnitus the real reason I stumbled upon Dr Sinclair and nr. People I have known say I don’t ask them to repeat themselves as often as I used to and I stopped talking as loud as I used to. I have to take their word on that. But I was precataract and now I have gone back to driving at night. My hair color has returned. I am full of energy and desire. High marks to Dr Sinclair and nr!
@@bombadeer8231 WHEN you say NR do you mean NMN and if so how much is the dosage that u take per day ? THANKS IN ADVANCE
Just started listening so I haven't heard your conclusions - but I love the idea of fact-checking and reality-testing Sinclair's claims about this. I do want it to be right because it provides a clear path for research in longevity.
As an interested non scientist, the clarity of your review and conclusion is refreshing. Much appreciated!
"backup copy of youthful epigenetic information" : I'd love a video dedicated to that!
And congratulations, as usual, on yet another excellent video - technical and clear!
Thank you for explaining the paper in a visual way!
This is a great explanation not only of the paper itself, but also the gaps, especially using Yamanaka factors to reverse epigenetic changes as no doubt those factors impact a lot of other cellular mechanisms too. As you suggest, the only way to really test it is to change the epigenetic markers themselves directly, and only them, in both directions, and see what happens to the lifespan of the mice.
i almost have a heart attack at 3:21
Me too😂
Was just hoping you’d make a video on this!
Fantastic video.
Interesting. Dr. Sinclair also mentioned that a primate study testing the ITA was also ongoing at another lab with those results available in another few months. If successful human trials would be a couple years away. Without an ICE equivalent of the mice presumably on naturally aged subjects ?
"backup copy of youthful epigenetic information": is this in *all* young tissue or just predifferentiated tissue?
Using the Yamanaka factors to reverse the age of cells in mice (and neurons, no less) through restoration of a youthful epigenome was already lucidly demonstrated in David's study where he restored vision in aged mice and regenerated their optic nerves.
there was a prof with spanish name who prolonged life in lox-cre mice also, if i'm not mistaken
@Roman Goff
Not really!
Its more like healing damage by injecting stem cells.
The Yamanaka factors simply make stemcells from ordinary cells.
So it hasn't anything at all to do with aging.
Nothing Sinclair has done so far reverses aging.
What he does is showing that epigenetic damage to cells is similar to aging in effect. But that's not even showing that it's the same as the epigenetic changes of actual aging.
It seems clear that aging has something to do with epigenetics. That's why the epigenetic clocks of aging works!
But it likely that utilizing the Yamanaka factors just erases the epigenetic information. Then the cell itself builds up the new one, like all stem cells does, directed by its environment.
Another, and perhaps better,way to get that result would be to let the damaged cell die. And create a new one from stemcells, in the normal way.
So, activate your pool of stem cells instead of making them from old cells!
We’re getting close, very close and aging is a disease of a cumulative damage and mistakes, and unless repaired the end is not so gentle and kind.
I've just started reading Sinclair's book the other day! "Interesting" idea about ageing being a preventable (and a) disease, to say the least... 🤔
Essa ideia já existe há uns 20 anos... Só não era popular. Aubrey já falava disso...
The DNA breaks made to the ICE mice were in non coding areas of the genome.
Nice video and very cool channel and format! :)
I recently discussed this with my colleagues at a lab journal club and there seem to be several things that are either not discussed or seem a bit peculiar about this paper:
1. The authors claim no changes in the cell cycle (of cells that with 10% in S phase already seem almost non-proliferative before even starting), but at the same time show that cells go into senescence (which would typically manifest in an increase of G1 cells) after the treatment. Lack of change in cell cycle and senescent cells seem self-contradictory, but this is not really adressed.
2. The authors don't discuss the saturation kinetics of DNA damage repair networks, but only show that there are no mutations at the sites with Ppol induced damage. While this tamoxifen treatment is chronically ongoing for 3 weeks, lowly abundant DSB repair factors that usually have to deal with 10-50 other DSBs per cell per day are pulled away from those sites and lack of repair of other DSBs may cause mutation at sites that are not investigated.
3. In the epigenetic changes they show in the heatmap, there is no change in H3K9me3, but then in the subsequent figures with the Yamanaka factors it suddenly goes down with ICE treatment and up again with the 'rejuvenation'. How does that align?
4. As you also point out it seems odd that you would not show either lifetime extension or pictures of these magically rejuvenated mice after OSK treatment. Have to wonder why.
Great additions to the discussion!
What are your thoughts on the paper mentioning the reasoning they did not utilize CRISPR?
Hey I saw your old video on NMN, are you still taking it? And would you recommend it for someone early 20's? Unsure how safe it is
No, it would be a waste of money at your age and just use it later in life maybe around 38
If you think about how many organs you could test, multiplied by how many epigenetic markers you could test, there's enough combinations such that you could test a ton of them and pick out the one that makes the AAV treatment look good, which may have just occurred by random chance. I'd like to see many more combinations than this one mark on liver cells tested. David Sinclair has a history of misrepresenting research results and we need to be very careful in evaluating his work.
Could these reversing principles be applied to reversing the affect from dying brain cells in Parkinson's Disease patients?
Chronic pain would be nice to fix before Parkinson’s
Yes. It is possible to use the Yamanaka factors not only to restore youth in cells, but to make them regenerate as well (including neurons).
@@JZGreengo both would be good ... but chronic pain caused by what?
yes and no, u need to identify the actual cause, cus stem cells rejuvenation its more like repair the damage that already there not fix or get rid what things that cause damage
The sound you made when You talked about p53 freaked me out, echo
The spooky insert with weird echo has scared the bejesus out of me. WTF!?
I feel I can say that David S.'s failure to explain is not at fault, as the study had the task of demonstrating that through the double-strand break there were typical signs of cellular senescence in response. moreover, I don't think that during biological aging it goes differently, the fact that every individual experiences aging in a different way and with many common traits such as wrinkles and damaged skin appendages proves it. with esteem Sheekey .
At 00:35 had to turn off cause was too loud & am trying to shower at my house & i dont want to be rude to those around me. Seemed like a great video tho ill try to watch it later today
3:20 using headphones and those freaked me out 😂😂
What this theory or I think it's will be to say more accurate to say, hipothesis, do not cover it's Mobile Genetic Elements.
Methilation also used by the cells to inhebit activity of the transposons, retrotransposons, etc, less methilation - more MGEs activity. More MGE activity - more random inserts in the genome and what's worse it's seems that the MGEs can move among cells in the extracellular vesicles, which is just accelerating the effect.
wait, tamoxifene increases aging rate?
I don't think so, sounds like the ICE mice were specially modified to have that specific reaction.
@@px43 No, the ICE-mice have been designed to age faster when given tamoxifene; the drug doesn't promote aging otherwise. In the ICE acronym, the "I" stands for "inducible", which means that epigenetic damages are induced only when the mice are given tamoxifene.
What about kydeny disease!!!
I'm no biologist, but it seems entirely invalid to use the reversal of "induced" damage to conclude that reprogramming can reverse *actual* aging.
As we can see, old age sucks. Time to get young again and back on our feet! I think Foxo4 DRI and Epitalon and Alpha Ketoglutarate Acid is the ones. Do you agree?
The subject is so interesting, but sadly I could understand like two thirds, not sure is it a mic or pronunciation..
You scared me at 3:20 twice 😂
Didn’t they basically lie in their conclusion then? They didn’t prove that they provided DSBs.
I really like your content though I must admit personally I wouldn‘t add the silly snippets, they are kind of distracting
One theory to rule them all is rarely correct.
Ah yes indeed. The unified field theory nerds are trying to turn lead into gold.
Thanks for your sharing your thoughts. I‘d like to note that I think your video could have benefited from speaking a little slower. If you‘d taken 17 minutes, you‘d have still cut to the chase. LOL. Still, nice work.
1st from Taiwan
Why is your name in Korean? 타이완에 사는 한국사람인가요?
@@kevinhuxley9252 I’m a Chinese live in Taiwan. Complicated? It’s a long story .I like many things about Korea including 한문 watch Korean drama or movies on Netflix .foods in Korea restaurants. Relative healthy due to fermented
Great. Stay safe during this unusual cold snap hitting Taiwan.
If only David Sinclair had more credibility it would be more promising to me.
Forgive my rashness in commenting. one last thing: in support of David S.'s theory there is also the administration of exogenous telomerase to mice which effectively brought the length of the chromosome telomeres back to juvenile levels but generating tumors of all kinds. this makes us understand that the cell, even if with young and long telomeres, once aged did not have enough information to be able to benefit from them, generating aberrant tissues.
Slow down aging or reverse it because if it's the second could we in few years find an away to make an 70 years old person to look like his 25s or 30s because that's what reverse aging means literally turn back your biological state.
What. I find interesting is that some people are totally opposed to living longer. Altos labs came out and said that they weren’t trying to make people live longer they were just trying to cure diseases.
That might be part of the reason why David Sinclair research is being opposed, it’s because he is challenging deep seated core beliefs in so many people.
Majority of the researchers who are working on reversing aging is saying the same thing. Because that is what would be acceptable to governmental regulatory agencies and society in general. But we all know what they are trying to achieve. When any of the drugs/therapies become available, I am sure doctors would find a way to administer it. All the people who are involved in the field have a personal stake it in. And I don't mean just the financial incentives. What good is money if you are dead?
I thought Rapamycin was already pretty good at reversing age but not many Doctors know what it’s supposed to do let alone write a script for it to reverse ageing.
Wouldn’t it be better to tackle the ageing problem head on and declare it a disease?
Tackle the root cause of most disease which is ageing rather than treating an ageing disease when it finally appears.
It may be so that that rejuvenating cells is easier than curing old age diseases. For example: cancer (or dementia or hear disease etc) is difficult to cure especially late stage, but if we could rejuvenate cells and drastically reduce the cancer probability well then the question becomes, should we do it? The side affect is you live longer in a younger body that does not age. Question becomes: can we accept the side affect? So researchers and companies avoid talking about this side affect due to stigma, but my guess is this will change in the next ten years.
@@orhanmekic9292 Imagine if you could rejuvenate cancer cells so that the epigenome changes that operate a cancer cell get unwound to a younger state. ie the cancer cell transforms to a younger normal cell.
I have seen a fridge on Instagram in David Sinclairs lab where green senescent cells turn into normal white cells after being treated with Yamanaka factors.
I learnt what reporter genes are after watching Sheeky science shows. I am assuming that a green petri dish means that reporter genes that detect senescence are being turned on which makes the cells turn green.
I think I have heard David Sinclair say that age reversal makes cancer go away(well probably in a petri dish to start with)
I am thinking that a fast way to bring age reversal mainstream is to cure cancer with the unavoidable side effect being that you become 50% younger.
I am working in molecular regenerative therapy and anti-aging , looking for funds
the fact that yamanaka factors kind of rewound means that there is a kind of memory about the initial state. That memory however can not (yet, at this stage of evolution) be a materially encoded piece on the level of DNA. That memory is vastly more complex than a "backup copy" and likely to be found on a "differential" level that is much more abstract, and partially, immaterial.
In fact, if you take, just as an example, a stack of self-organizing maps (kind of neural network), where each higher level learns properties of the next or several lower levels, this can be seen as abstraction and actualization, much in the sense of Kant's idea of templates.But here, as in the cell, both interpreted as associative networks, it oes not make sense to ask "Where" sth would be stored.
They are so close, but still don't get it.
Long story short, what did they feed the rat so I can start supplementing with it asap! 😁
ICE mouse is still young, just looking old. We need to reverse real old mouse.
This is what we need scientists to keep doing research and experiments on. The miracle of feeling and looking young all the way until we die. Not having to worry about old age appearance getting you rejected asking girls out. Getting more chances in the bed.
We need youth for life. Save the sex life
Keep it holstered buddy
@@BK-dy8jk well would anyone wanna have sex with an old 70 year old man because it never would be me
If David Sinclair doesn’t know what he is doing how did he manage to cure blindness in mice and get on the cover of Nature magazine. How does he get so many different labs to work with him?
Wouldn’t there be optometrists that look into the eyes of monkeys that are being treated for blindness and say look this age reversal stuff doesn’t work. Wouldn’t they say something?
@peter m
Stemcells can cure damage.
The Yamanaka factors make stemcells of ordinary cells.
It might be a viable treatment.
Although, I would prefer if we would find a way to activate our ordinary stemcells.
Nothing wrong with Sinclairs research here, as a treatment for damage.
Replacing old cells from stemcells should be a viable anti-aging method. If those old cells aren't genetically or epigenetically damaged, of course.
@@larsnystrom6698 David Sinclair's method for age reversal just uses three Yamanaka factors which means the cells keep their identity and don't turn into stem cells. This of course makes the treatment very safe and makes it possible to treat every cell in the body.
Hospitals, doctors offices and schools should be places where good nutrition is taught and provided not places that contribute to disease and obesity. It is crazy the hospitals are feeding people the very food that caused the heart disease, high blood pressure or cancer that they are treating. Every person in the hospital should receive some nutrition education before being released. Every doctor visit should be an opportunity to educate patients about how food choices impacts their health outcomes. The fact that doctors do not get nutrition training as part of their training makes no sense. Medicare and Medicaid should require nutrition education as part of patient care. Focus should be on food choices. Fasting should be investigated as a treatment for disease.
I really like your videos. I don't want to be rude, but I find it difficult to understand your accent especially as you speak really fast. Can you please try to speak slower in your future videos?
You can regulate playback speed on your device within RUclips
2:01 giggity 😏
Sinclair definitely needs a lot of scrutiny I think. But it’s interesting for sure.
Yeah kind of feel like he's sold out and is just hyping his own theories up in order to make a few bucks.
No your bias needs a lot of scrutiny. You need to be able to see the theory without the author.
Basically the ITA is just the Hallmarks of aging sorted in an hierarchical where some hallmarks are now cause and others are perpetuated effects. The ITA in combination with the Yamanaka factors here show that epigenetic programming and loss of information is a very solid theory to understand why loss of information happens and that we can restore it proven by this paper in mice.
The Theory super solid. The supplements pushed by ONE of its authers... irrelevant.
@@unholyquail4560
Oh, DEAR.
My bias doesn't need any analysing. I think you'll find that scrutiny is a fundamental bedrock of the scientific inquiry and must absolutely be applied here just like it is on any other workable theory in science and this is also what Mr Sinclair himself is doing. As for theory being 'super solid', nope, very little in science can be described as thus even when it provides benefits, as is always on the verge of being improved or replaced at a later date (for now, natural selection would be one theory, even general relativity now looks like it has a sell by date on it now). But I'm hopeful for sure; who doesn't want to live longer and be younger?!. I have also defended David on various channels including the NZ Doctor's (concerning the resveratrol incident). I hope his theory holds true and we can see reverse ageing happen in dogs and primates etc next, but until it is, I'm going to reserve judgment. But I wish him all the best.
That very loud sound effect around 3:25 was an unappreciated assault on headphone users. Please don't do that again.
Great videos generally. You should refer to him as Sinclair rather than David, imho. It is troubling, sorry
The aging process is too vast to isolate just a few factors. Even inanimate things age. Sinclair, et al, is basically a NIH quack. The fountain of youth will always be a money maker.
Well, there are beings that don't age. Like the immortal jellyfish. The greenland shark. Some see sponges. You're just repeating empty phrases like a parrot.
@@richardbreeze4911 Yeah, I know. But the fella who made the original comment doesn't seem to ;)
Inanimate things "age" because usually they don't have regeneration processes, a building could last for thousands of years with maintenance or "regeneration"
Not everyone is capable of enunciating. Those who aren't should have someone else narrate their vids.