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 :)

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!

i almost have a heart attack at 3:21

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.

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.

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.

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 ?

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... 🤔

Thank you for explaining the paper in a visual way!

I'm no biologist, but it seems entirely invalid to use the reversal of "induced" damage to conclude that reprogramming can reverse *actual* aging.

The DNA breaks made to the ICE mice were in non coding areas of the genome.

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.

The spooky insert with weird echo has scared the bejesus out of me. WTF!?

3:20 using headphones and those freaked me out 😂😂

"backup copy of youthful epigenetic information": is this in *all* young tissue or just predifferentiated tissue?

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 .

You scared me at 3:20 twice 😂

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

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.

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

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.

Was just hoping you’d make a video on this!

One theory to rule them all is rarely correct.

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

The sound you made when You talked about p53 freaked me out, echo

If only David Sinclair had more credibility it would be more promising to me.

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?

wait, tamoxifene increases aging rate?

Fantastic video.

What are your thoughts on the paper mentioning the reasoning they did not utilize CRISPR?

Could these reversing principles be applied to reversing the affect from dying brain cells in Parkinson's Disease patients?

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.

The subject is so interesting, but sadly I could understand like two thirds, not sure is it a mic or pronunciation..

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.

What about kydeny disease!!!

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.

I am working in molecular regenerative therapy and anti-aging , looking for funds

They are so close, but still don't get it.

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?

Sinclair definitely needs a lot of scrutiny I think. But it’s interesting for sure.

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

That very loud sound effect around 3:25 was an unappreciated assault on headphone users. Please don't do that again.

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?

Long story short, what did they feed the rat so I can start supplementing with it asap! 😁

2:01 giggity 😏

1st from Taiwan

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.

Not everyone is capable of enunciating. Those who aren't should have someone else narrate their vids.