"Breakthrough" = will lead to nothing of importance. I'll believe it when they do human trials. Sinclair's words afaik aren't a reliable source.

He's a professor at harvard medical school, has a phd, and runs his own research lab.You're some guy on reddit who likes to watch hentai, you're not a reliable source.

💀💀💀

TL;DR:

For a while the leading hypothesis around aging had to do with DNA damage through a variety of different means. However, this hypothesis was always on shaky ground, because we couldn't find direct correlations when we look at other animals with even more severe damage at much younger ages. The correlation was just hard to find, even though the theory made sense.

However, this research is showing that it actually seems to be epigenetic "noise". Basically, with time as epigenetic "switches" turn on and off they kind of become less and less "useful". Basically a lot of noise in their performance code making their specific purpose less efficient as all these epigenetic changes start to pile up.

What this research shows is when you use similar techniques used to create stem cells, you can "reverse" the epigenetic age, effectively "restarting it" by telling them to return to their original state before all the epigenetic changes. Think of it like a computer being on for a week slowly just getting bogged down until you reset the computer and everything is running clean again.

When they did this in mice, they found age reversal. Further, when they did the opposite, by increasing the epigenetic noise in very young mice, suddenly the mice started resemble old mice (frail, low stamina, grey hair, weight loss, etc), which is further evidence that epigenetics are indeed playing a significant role in aging.

What's wild about this, that if this is true, this is a very solvable problem. It would take the problem of aging down from the rank of baffling enigma, to something we can solve because much of the science needed to do these reversals is pretty well developed and understood.

Trials are moving onto primates. If we get the same results as we expect, this is going to lay the groundwork in a massive paradigm shift putting age reversal literally within reach.

Except I am not stating a purely personal opinion but rather have read some credible criticism on him before. Also your assesment of my person screams argumentum ad personam steming from own insecurity.

Average redditor contribution absolutely nothing and calling someone a expert in their field not reliable.

I mean man what are you smoking I want some.

And your argument screams even more insecurity than his.

David Sinclair, one of the main authors of this study, wrote a book called Lifespan which describes the epigenome theory of aging in more detail.

I recommend it- Sinclair argues persuasively that senescence should be thought of as not just a disease, but as the most important disease, since it leads to so many others- and he outlines a lot of promising-looking lines of research that may one day lead to effective mitigation or a cure.

Note, though, that while Sinclair seems pretty well-respected by other researchers, he does also have some pretty large financial stakes in anti-aging supplement companies, which could be biasing his work.

Great summary, thanks.

>Further, when they did the opposite, by increasing the epigenetic noise in very young mice, suddenly the mice started resemble old mice (frail, low stamina, grey hair, weight loss, etc), which is further evidence that epigenetics are indeed playing a significant role in aging.

This to me is the most fascinating and important part. Being able to shift aging both ways makes the “noise” argument very convincing.

That said, I’m checking my hype until the primate trials show the same results. It often seems like every new health or disease treatment out there works on mice and then we never hear about the treatment again.

This seems like a BFD, no?

He's definitely not well-respected. He has a following of biohackers, but many researchers consider him a snake oil salesman.

Cool, hope this leads to big things.

!RemindMe 5 years

I will be messaging you in 5 years on 2028-01-13 23:20:31 UTC to remind you of this link

8 OTHERS CLICKED THIS LINK to send a PM to also be reminded and to reduce spam.

^(Parent commenter can ) ^(delete this message to hide from others.)

I always thought that telomere shortening and tumour suppressing genes were the main causes of aging, has this been proven false?

Telomeres were also just a theory, based off observations of older people who aged well, and other species. That long telomeres prevent the cell damages as they act like a sort of redundant absorption for mutations. However, much like the DNA damage theory, it had a lot of conflicting evidence that made direct correlation hard to prove... It's likely long telomeres are more likely a symptomatic correlation rather than causal.

Tumor suppression probably also exists within the epigenetic side of things as well. As we age, our bodies get worse and worse at fighting things off. They replicated this by artificially aging the mice which suddenly got more tumors. So as the epigenetics of the cells get more noisy, so does their ability to precisely work as intended, thus more tumors.

Invoking entropy here is really stupid, I’m not sure why this tiresome trope persists in aging.

Aging is not a direct product of entropy. Aging is a product of imperfect upkeep/maintenance mechanisms.

Entropy is why maintenance is required in the first place. Want to see what really happens to an organism as a result of increasing entropy without maintenance? It’s called being dead, and rotting.

Organisms that are not dead have to constantly maintain themselves in the battle against entropy just to continue to function at all. So it isn’t entropy per se that causes aging. Increasing entropy causes rotting. And maintenance stops rotting, because it stops the growth of entropy.

Aging is caused by imperfect maintenance. That’s totally TOTALLY different. And there’s no reason why maintenance can’t be perfect.

Do cars and other machines need maintenance to keep from rotting because of entropy? Of course they do. Is it impossible to perfectly maintain an old car? Of course it’s not.

Crazy the editors at a journal like Cell would continue to allow this stupid misunderstanding of entropy and aging to be repeated.

Is slowing down the hallmarks of aging the same as slowing down aging, or is it just cosmetic? i.e., will you just make for a prettier corpse at ~120.

Entropy is the tendency of any system to devolve into chaos given enough time. It isn't chaos itself. The breakdown of the epigenome with age is the maintenance system slowly changing over time until it doesn't work anymore. That is entropy. Now, biological systems aren't closed, and we could ship of Theseus ourselves until the end of time, but without that reset, entropy will creep in

If you'd like to see a video on this topic, consult my recent post of a David Sinclair vid. He's the senior author of this study. My post has a lot of views but no comments yet. 😂

Wrong.

Entropy is disorder. The Second Law of Thermodynamics holds that entropy must increase over time in all closed systems. That is all.

Biological organisms are not closed systems, so like you said, the Second Law does not apply.

Entropy increasing over time does not cause aging in organisms, it causes rotting or decomposition. This is an extremely rapid process. Without maintenance and upkeep, cells would rot in days, hours, or even minutes in some cases. Tissues therefore rot quickly too, once they are mostly-closed systems and no longer receiving input energy and therefore no longer running maintenance via metabolism.

Aging is only caused by the slow accumulation of errors and failures in the maintenance processes. It is not directly related to increases in entropy, any more than any other slow changes in an organism over time are. The error here is reasoning by analogy too closely with non living machines. Machines like cars do not have metabolisms. They rot extremely slowly, over decades, not hours or minutes.

Here’s another way to see it: You wouldn’t say that growing from an infant into an adult is because of entropy, would you? Yet that is very similar to what causes aging: imperfect maintenance of the organism’s existing structures. In the case of growth and development, those imperfections lead to changes that are “positive” or “desirable” from our subjective viewpoint. But that’s just arbitrary. Aging is just as much a part of “natural” development as, say, puberty.

Talking about entropy at the level of aging and development in an organism instead of at the level of metabolism is an error in the basic unit of analysis.

!RemindMe 5 years

It's pretty old news, Veritasium covered the story on YouTube

The article's behind a paywall; does it say when the primate trials begin? And how accurate are primate models? I heard that mouse models translate to humans less than 10 percent of the time, whereas testing on human cells does so 81-87 percent.

If this works as described I’m wondering how society’s are going to deal with a change as massive as this and not shatter under the stress of it. If the death rate drops and the Birth rate stays the same we will need more resources. Will there be enough? If we get a second life after 60 years of toil will it be one of leisure / pursuit of personal interest or will it be 60 more years of toil? Societal changes will likely be huge and the disruptions larger than one might think.

I think with the advancements of this type of tech there will also be advancements in other types of supplemental tech. Lab grown food, terraforming, etc. I’m not worried about resources running out for humanity once we reach AGI and ASI.

I also think as more and more of our workforce gets automated we will have to institute UBI or something similar, but ultimately we will become a post-scarcity society where people don’t have to work at all and where everyone will be able to cheaply acquire or create anything they need.

What really fascinates me are the social ramifications that perhaps even our generation will experience: imagine being the same physical age as your children AND grandchildren. That’s a really weird possibility that seems like it might be on the table for us. How do marriages work if you’re living 250 years? How do families work or friendships? How does crime and punishment work? Are we going to imprison murderers for centuries? Will people start wearing full mech suits knowing that if they die it’ll be hundreds of years of life missed instead of 50-70 years?

As you say there will be very large disruptions, tons of which we probably won’t even anticipate. The near-ish future is gonna look completely different to the world we’ve grown up in. The 90s and 2000s will seem literally medieval compared to the 2060s. I really hope I’m here to see it all.

Everything is coming so much earlier than expected

Confidently incorrect.

Also does it say anything about human organoid trials begun

good luck with that, see "Aging clocks, entropy, and the limits of age-reversal"

[deleted]

Good point, thanks!

Sinclair video

Breaking my brain 🤯

Organisms aren't closed systems, entropy as some inescapable feature doesn't apply

If entropy was a valid argument we wouldn’t exist as we are the result of fighting entropy.

What is epigenetic noise???

Link?

Yah, I was excited until I read that the scammer known as David Sinclair was behind it. That's unfortunate.

A bit of theory crafting:
 
The majority poor people of the world can't get enough food or minerals to sustain their bodies. They suffer from malnutrition and easily curable diseases that will kill many of them.
 
If its pill form and the rich nations get this we may have a new divide. The ones that live longer vs the ones that have short lives, we may have a new form of protests/terrorism until the rich nations figure out how to get the poor nations of the world improving conditions for their people.
 
If this is available only to the 0.1% of the wealthy of the world, I assume they will have to start going into hiding to avoid controversy until it comes to the masses. Same issue of protests that may lead into terrorism until it becomes cheap enough for more people.

> epigenetic

From googling: “epigenetic noise,” which disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity.
 
My take: corruption of replication which adds "noise" which brings in increasing inefficiencies over time to eventual collapse of systems?

Replication of what??? And why corruption of replication happens??? Why can't there be replication without this corruption???

Nonsense. Reread my last post until you understand the difference between aging and rotting. They are not the same thing. If you can’t see why, you don’t understand the relationship between biology and entropy at all.

It’s frankly both astonishing and discouraging how difficult this is for people to grasp.

Not difficult to grasp. These people aren't talking about maturing or getting older, moving from 15 to 20. They are talking about ageing. Cells rely on entropy to survive by decreasing the entropy inside themselves at the expense of increased entropy in the surroundings. As we age the ability of the cells to do this decreases and internal entropy increases until the cells die. The reason this occurs is likely due to genetic changes as we get old

Going through your post history, you need to learn how to google, read multiple links and come to your own conclusion like the rest of us do... instead of having everything spoon fed to you. Stop being lazy. There is nothing wrong with asking a question but your post history reveals how often you ask others to do the work for you.

[deleted]

It uses the same technique used to turn revert normal cells back into their stem cell state. Beyond that, I'm not entirely sure on the details.

[deleted]

[deleted]

Advancements in artificial intelligence will usher in an era of post scarcity, specifically energy post scarcity as companies like Google DeepMind begin to tackle fundamental problems in the realm of fusion.

>come to your own conclusion like the rest of us do

Pretty sure people that draw their own conclusions based on due diligence research are the minority on the internet, not like "the rest of us".

No idea on the specifics but all I got out of it was that it leveraged the same sort of mechanism. I think I recall reading something about using peptides to activate it? I could be wrong.

Again, fundamental misunderstanding that conflates two distinct processes.

Entropy increases constantly if a system is closed, so exporting it from cells and tissues and whole organisms is the essence of what metabolic upkeep does. It’s called being alive instead of rotting.

Aging is an entirely secondary effect of the upkeep itself. If upkeep were perfect there would be no aging. Organisms would remain functionally identical and unchanged over time. This is easy to achieve with simple machines like cars, and some species come close to achieving it too with “negligible senescence”.

A directly analogous process to aging is growth and development.

Growth and development are functional changes. You can think of them as “better than perfect upkeep” if you like. But conceptually they are not much different than aging: the process of using energy and inputs to power metabolism and export entropy is not perfect, so there is slow drift in the form of the organism m, but this occurs over a much MUCH longer timescale than rotting/decomposing.

Again, think of a car: if you let it sit without putting anything into it at all, it rots. THAT’S the second law, and entropy just increasing unabated. Alternatively, there is maintenance and upkeep that can keep a car in perfect condition forever. But what’s the difference between upkeep and upGRADE? Nothing, as far as entropy goes. Upgrading a car is just using energy and inputs to do a bit more than keep it exactly unchanged.

Don’t just take it from me. Aubrey De Grey is a staunch advocate of my exact position on entropy, because he of course understands it.

Not well respected he's a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. He's literally at the pinnacle of his field. Show me evidence of his derision amoungst his fellow researchers.

I don't know anything about him but I studied biochemistry and I'm very interested in thermodynamics. The cell isn't a closed system. This allows it reverse its internal entropy at the expense of increasing entropy in its surroundings with a net increase in entropy of the universe. For example glucose is converted to CO2, an increase in entropy, and this entropy used to provide free energy that the cell uses to repair itself and make proteins. As the cell ages it is less able to do this. We don't know why but it is evidently related to genetics. As this decreased regulation increases the cell is able to function less and less until it dies. Take this and scale it up to a person and it manifests as ageing. You were conflating the person's use of 'getting older' with 'growing up', when they were speaking about getting old.

It's not hard to understand.

Cell is certainly quite prestigious, but as I'm sure you are aware from your own field, the prestigious journals are more interested in sensational findings than in scientific rigor and reproducibility. Moreover, the peer review will depend on the specific reviewers and there's quite a bit of backclapping going on in this particular field of research.

That said, I cannot speak to this particular study, as I have not yet read it myself.

Being a professor certainly seems respectable from the outside, but the universities are full of them nonetheless, and among peers the title is worth less.

He has built a career on sensational (irreproducible) findings, overinterpretation and exaggeration.

Here's your link for proof. I know of few researchers who have been called out in such a fashion.

Sure there are a lot of adjuncts at colleges but there aren't many co-chairs of their department at Harvard.

I'm not trying to simply appeal to authority here, but that is a very lofty title at very respected institution. One article from Charles Brenner, a highly respected researcher in his own regard at an equally well regarded research institute- while highly troubling- doesn't totally convince me that Sinclair has lost the faith of a majority, or even a large portion, of his colleagues.

I guess my question is if he was such a quack, how does he keep his job and how does he keep getting published in highly prestigious journals such as Cell?

My guess would be there are opaque internal politics involved that those not behind the scenes aren't privy. Which would make this seem more like a collegial spat or personal vendetta settling than wholly honest critical peer review. But I'm very open to being wrong.

I'm sorry to pester, but I'm largely unfamiliar with the intricacies of this field. May you, or anyone who works in the field, please provide some more sources of legitimate criticism for Sinclair from his peers?

Even highly acclaimed research institutions and journals unfortunately care mainly about money and exposure. Sinclair undoubtedly creates research papers of high "impact" - in the sense that they are sensational and oft-cited. It's just that no one else can reproduce his findings and that the actual clinical impact is unimpressive. Moreover, while appearing reasonable at a glance, many of his statements fail under scrutiny - the text I linked by Brenner really does quite a good job in this regard.

There is (unfortunately) not a culture of actively trying to disprove the research of others in today's scientific research, even though it is in principle one of the pillars of science. The fact that Sinclair's claims are so over the top that they merit a response like this truly is special.

I'll keep on asking people what i wanna ask....and if they wanna answer they'll answer and if they don't wanna answer... they'll not.... It's simple they'll not respond to it... instead of wasting a minute or 2 in first searching my post history and then in writing a long-ass paragraph on not answering it... You could've chosen not answering it and leaving it as it...but wasting your 2 min was more important and natural and wise instead of answering it and thereby helping someone else to know more abt this interesting topic and in addition not only you did the above mentioned things but you also chose to belittle them... If you were that bothered to answer why didn't you just leaft it as it is without answering it??!!! Someone else might have answered it or perhaps wouldn't have answered it ... But I'm sure nobody would have write a long paragraph on refusing to answer and then belittle someone....

Well I’m a fucking scientist with a PhD from an R1 university and Aubrey de Grey is the most iconic gerontology theorist in the world. Not sure why measuring dicks is relevant, the concepts are plain enough to speak for themselves.

You’re still just not getting it. Not sure why, I guess you’re either not actually reading the posts or just dim.

Anyway, I explained it four times, and you’re still not grasping the core idea of the distinction between the levels and timeframes of separate but connected/nested processes.

It would be like confusing the idea of why an oven needs fuel to maintain a constant temperature above ambient temperature vs the idea that in order to raise or lower the temperature of the oven you need to change the fuel consumption rate. in this analogy, raising the temp is analogous to growth/development and lowering the temperature is analogous to aging. It’s not a perfect analogy, but the parallel is strong enough that it should be self evident now why metabolism and aging are different.

Ok, that’s now five different explanations of the same core concept.

If you can’t see why a flow of inputs is different from a stock whose level either grows, shrinks, or remains static as a function of the flow’s rate, well, you’re just too dense for me to help you understand the difference between metabolism and aging, and why entropy applies to the former but not the latter.

Give a man a fish and you feed him for a day; teach a man to fish and you feed him for a lifetime.
 
You are actively doing yourself a disservice by not looking it up yourself. How do you know the one or two comments you get are accurate or biased or trolling? You can't see it as you see my comment as an attack but I am giving you good advice that will help you in the long run.
 
In short: Learn to fish.

Well it's unfortunate that you have such a poor grasp of thermo despite spending 8 years working toward a PhD, but I guess you'd be the secon\\d idiot on reddit that I've seen arguing incorrectly about the thermodynamics of the cell. I suggest you go and review first year physical chemistry. You remind me of a clown similar to you over on r/biochemistry arguing against the other users about whether the cell is a closed system.It's also a little funny that you resort to insults because you get so easily flustered explaining your misunderstandings with poor analogies. No one is confusing the difference between metablism and ageing. However you seem to be confused about the difference between cell growth and ageing. Cells grown and maintain themselves. This requires free energy which is derived from the decrease of free energy in molecules like glucose, producing simpler CO2. This results in an increase in the entropy of the surrouning environment and a decrease within the cell. As cells age the ability of the cell to maintain itself decreases, barring senescence we don't know the precise mechanism of why, but it results in increased entropy within the cell. Eventually the cell is unable to maintain itself and dies afterwhich it rapidly increases in internal entropy to a point equivalent to it's surroundings.

,,iMpErfecT uPkeEp/mAinTEnance mEchaNisms'' occur because the cell increasingly loses its ability to resist the increase of internal entropy. That is ageing. That is quite different from growth and development which occurs, not because of dysregulation, but because of normal, regulated gene expression, with no notable change in internal entropy. I find it amazing that you think 'imperfect maintenance of the organism’s existing structures' lead to maturation from an infant to a teenager. And that normal growth is equivalent to a 40 year old growing into a 90 year old with liver spots and cancer.

If you would give a comparison like the development of larger muscles during puberty to the onset of diabetes or male pattern baldness then I could see where you're coming from and say that is probably an example of antagonistic pleiotropy but instead you liken it to hearing loss and back pain.

Here's a paper that discusses it further. I'm guessing you won't read cuz you seem like the type to only read you own research and laugh at your own jokes. Here's a notewrothy quote: "The mechanistic linkbetween entropy generation and pathogenesis has been confirmedin metabolic diseases (simple obesity, diabetes, metabolic hypertension".

And here's a list of other research showing the link between ageing and entropy.

You yourself said exactly what I've been trying to explain in your first comment:

>Aging is a product of imperfect upkeep/maintenance mechanisms.
>
>Entropy is why maintenance is required in the first place

Then you go on and contradict yourself repeatedly.

Actually it's also kinda funny you said 'entropy is disorder' in a debate while unironically calling yourself a scientist. Or that you described a closed system as only being able to maintain its internal entropy, when, by definition, it will maintain the same entropy or increase it. What a joke.

Here's a sneak peek of /r/Biochemistry using the top posts of the year!

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Lol at the dumbfuckery. Your last paragraph is not even coherent. You’re embarrassing yourself, and I’m not going to explain the difference between a stock and a flow a sixth time.

Others can read and understand the explanations I gave. They’re trivially simple. You’re just a moron who got called out and is now doubling down on everything you didn’t understand the first five times around. Your blather about internal cellular processes shows you don’t have any clue what level of analysis is even relevant.

Not coherent? Nah you just can't read or perhaps English just isn't your native. And did you look at how you spoke or your own analogies? Idiots like you who can't reason or admit they are wrong or resort to ad hominem attack when in a debate hold back scientific progress. Let's hope you never try to publish research cuz I can bet you'd resort to character assassinations and smear campaigns when your papers don't pass peer review. Just stick to bench work. 👍

I'm embarrassing myself.......on reddit......where users are anonymous........ah boy.