Chemically induced reprogramming to reverse cellular aging

You’re being generous. He’s made it clear that his priorities are money, money, and money, and he seems willing to do, say, or publish just about anything to make more of it. He reminds me of a used car salesman.


which of these if any has to do with NMN ? Which i thought for sure he promoted though not necessarily for life extension .

I worked with many Brenner types at DuPont in R&D. They were the worst teammates to work with dragging the group down. Never really contributed positively to new discoveries… It was the optimists who drove new advances even though sometimes their ideas were too far out.


I certainly believe that Dr. Sinclair has made some questionable decisions, but regardless of his flaws he’s probably done more to raise awareness of the aging field than anyone. I’m sure the right thing to do would be to admit the flaws in his data and not be so hyperbolic, but I’m sure he feels that it would damage his image. I think admitting he was wrong might severely damage his reputation. While I take what he says with a large grain of salt I’m also grateful for what he’s done getting the message out to the general public. He’s gotten peoples attention and that’s a good thing.


Debate is important and necessary but I find him quite hard to listen to. He’s combative and dismissive or at least was on the couple of occasions I’ve listened to him debate. I felt incredibly sorry for Brad Stanfield the first time he invited him on his show. Brad looked like a deer in the headlights. I do believe Brenner is a good scientist -he strikes me as very conservative and traditional-but he’s just as full of his own hubris as the people he’s debated. I’d love to see more debates but I wish his approach would be a bit less aggressive and a bit more measured.


fantastic detective work! can I ask what is your professional training?

I disagree with Charles Brenner’s overall negativity, but he I respect the point that he has published a paper going into the details of the issues over SIR2.

I would tend to agree, however, that I would not want him “on my team”.

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TGF-β is very interesting in aging, but it has very complex functions, It is in some cells a driver of aging, and is up regulated in aging and cancer. But “TGF-β signaling elicits complicated effects (e.g., beneficial or detrimental), including neuroprotection, gliosis, hydrocephalus, and vascular fibrosis, depending on the cellular, spatial, and temporal context”. So it needs to be balanced in a way that reminds me of mTOR. It definitely needs more research before it can be targeted for longevity.

The Conboys have also studied it and its relation to aging.

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It is irresponsible of David Sinclair to make these kind of claims. I still think he’s been a force for good overall, but I can’t help think that this is going to lead to people trying these cocktails. I don’t understand why he can’t be more measured with his language. It looks like an interesting first step but that’s all it is.

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With all due respect to Matt, he should probably avoid being named in the same article as Brenner, who seem to have David Sinclair living rent free in his head. It seems to affect his language saying things like “nonsense”, show some respect to David Sinclair and achievements, least of all making many of us interested in the field?

Also the Brenner Vs. Sinclair saga has to end up in a cage fight, I would buy tickets… :rofl:
They remind me of the two magicians in The Prestige.


I think Matt is just getting tired of the hype that David’s announcements generate all over the Internet and news… the types of stories like those below are all over the web now, which might be helpful for getting people excited about longevity research, but I think most people will be disappointed by the reality, and that breeds skepticism and “longevity” fatigue because the promises never come true.

It seems like David comes out with these every 6 months…

Age Reversal Breakthrough: Harvard/MIT Discovery Could Enable Whole-Body Rejuvenation

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It’s because David Sinclair is the poster boy for Longevity research. He popularized resveratrol, everyone knew about that, and gossiped about red wine, regardless how wrong it was. The problem you are mentioning is for everything, people just need critical thinking. It just not a good look to dogpile on Sinclair who is a Harvard scientist regularly publishing in Nature with his lab.

Instead I think Matt should make David join his cause, that would be better…

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Also it is very common for people like Sinclair to have weird beliefs, like Linus Pauling.

Imagine a black box which, when you pressed a button, would generate a scientific hypothesis. 50% of its hypotheses are false; 50% are true hypotheses as game-changing and elegant as relativity. Even despite the error rate, it’s easy to see this box would quickly surpass space capsules, da Vinci paintings, and printer ink cartridges to become the most valuable object in the world. Scientific progress on demand, and all you have to do is test some stuff to see if it’s true? I don’t want to devalue experimentalists. They do great work. But it’s appropriate that Einstein is more famous than Eddington. If you took away Eddington, someone else would have tested relativity; the bottleneck is in Einsteins. Einstein-in-a-box at the cost of requiring two Eddingtons per insight is a heck of a deal.

What if the box had only a 10% success rate? A 1% success rate? My guess is: still most valuable object in the world. Even an 0.1% success rate seems pretty good, considering (what if we ask the box for cancer cures, then test them all on lab rats and volunteers?) You have to go pretty low before the box stops being great.

I thought about this after reading this list of geniuses with terrible ideas. Linus Pauling thought Vitamin C cured everything. Isaac Newton spent half his time working on weird Bible codes. Nikola Tesla pursued mad energy beams that couldn’t work. Lynn Margulis revolutionized cell biology by discovering mitochondrial endosymbiosis, but was also a 9-11 truther and doubted HIV caused AIDS. Et cetera. Obviously this should happen. Genius often involves coming up with an outrageous idea contrary to conventional wisdom and pursuing it obsessively despite naysayers. But nobody can have a 100% success rate. People who do this successfully sometimes should also fail at it sometimes, just because they’re the kind of person who attempts it at all. Not everyone fails. Einstein seems to have batted a perfect 1000 (unless you count his support for socialism). But failure shouldn’t surprise us.


Its interesting, because Matt has said in past interviews that he agrees with David on probably 95% or 98% of the science. Its just when David steps over the line that isn’t supported and starts claiming “age reversal breakthroughs” that they differ.

I prefer Matt’s more measured response but I can also see why David does it… have to keep the lab in the news, have to keep publishing, have to keep the positive news articles around the technology to keep the investors putting money into all the startups he’s spinning out…



today @davidasinclair is telling the world that he has achieved age reversal with chemical cocktails


Sad sign of the times this even needs to be said, but headlines claiming @Harvard researchers developed a chemical approach to reverse aging are not true. Nobody has a drug to reverse aging. @elonmusk and everyone else, please don’t start taking anything based on this nonsense…


Grateful to share our latest publication: We’ve previously shown age reversal is possible using gene therapy to turn on embryonic genes. Now we show it’s possible with chemical cocktails, a step towards affordable whole-body rejuvenation 1/17…

Title of the Article:

Chemically induced reprogramming to reverse cellular aging

Fourth paragraph of the article’s introduction:

The ability of the Yamanaka factors to erase cellular identity raised a key question: is it possible to reverse cellular aging in vivo without causing uncontrolled cell growth and tumorigenesis? Initially, it didn’t seem so, as mice died within two days of expressing OSKM. But work by the Belmonte lab, our lab, and others have confirmed that it is possible to safely improve the function of tissues in vivo by pulsing OSKM expression [22, 23] or by continuously expressing only OSK, leaving out the oncogene c-MYC [7, 8]. In the optic nerve, for example, expression of a three Yamanaka factor combination safely resets DNA methylomes and gene expression patterns, improving vision in old and glaucomatous mice via a largely obscure mechanism that requires TET DNA demethylases [8]. Numerous tissues, including brain tissue, kidney, and muscle, have now been reprogrammed without causing cancer [7, 8, 22, 24, 25]. In fact, expression of OSK throughout the entire body of mice extends their lifespan [26]. Together, these results are consistent with the existence of a “back-up copy” of a youthful epigenome, one that can be reset via partial reprogramming to regain tissue function, without erasing cellular identity or causing tumorigenesis [7–9].

Winner of the accurately informative tweet award - Kaeberlein. He said it is the headlines that are the problem. He made no statement on the merits of the article.

I am reading and re-reading the article. Until then, I will suspend judgment.


The actual journal article is solid. They hype around it is of course super wild. And I think a lot of big names don’t like that Sinclair sometimes fans the flames of hype a little. Most scientists are always downplaying their work to avoid having anyone think they’re claiming anything more than what is 100% supported by evidence.

do you think SIRT2104 is the key ingredient in the study? the rest of it are supplements that you can buy on Amazon, it seems.

Here’s a list Sirtuin activators-

They’re all sirt1 and sirt6 activators.

Sirt3 is below:

Honokiol (magnolia), dihydromyricetin, and salidroside (rhodiola), among others.