Review of new David Sinclair paper, supplements & anti-aging glitz

Who is David Sinclair and why is he all over the media related to anti-aging efforts?

This post is my effort to fact-check Sinclair’s statements in the context of the broader rejuvenation arena. In the process I also review his most recent paper from my view as a stem cell and cancer biologist interested in reprogramming.

David Sinclair | New Sinclair anti-aging paper | Reprogramming | OSK-mediated rejuvenation | Criticism of Sinclair hype | Lifespan | ChallengesDavid Sinclair supplements | References

David Sinclair, anti-aging
David Sinclair giving an anti-aging TEDx talk. Screen shot of YouTube video.

David Sinclair and anti-aging

David Sinclair is a respected Harvard professor.

His work presents a kind of puzzle as his published research is generally interesting and important, but at the same time, I believe that he hypes anti-aging science.

In addition, he promotes unproven supplements and lifestyle regimens that are supposed to battle aging. At the same time he takes such supplements and writes, talks, and tweets about how well they seem to work.

His substantial commercial roles and interests in anti-aging efforts are also important for context here.

David Sinclair
Could Harvard Professor David Sinclair be too excited about anti-aging research?

Review of new Sinclair paper

He has a new paper in the journal Aging. It has some surprising statements like moving towards “whole body rejuvenation.”

In humans.

Some form or other of the word “rejuvenation” is used 35 times in this paper. This struck me in reading it, probably in part because in dealing with unproven stem cell clinics over the years, one of their favorite words is “rejuvenation.”

Is rejuvenation a scientifically rigorous term? If so, how precisely has it been defined?

Let’s take a look at the new paper and the context.

New paper tells mostly an old story on reprogramming

Some of the data in this paper are interesting, but the findings are generally not so new in my view. They can reverse aging-related phenotypes in cells by reprogramming.

Of course, a vast amount of past reprogramming work by dozens of other labs has already covered much of this. For example, many readers of The Niche will probably recognize the OSK-type reprogramming cocktail. It and similar cocktails have been used so many times before over the past 17 years and it’s also showing up in Fig. 2 here in the Aging paper. For reference, OSK means the combination of OCT4, SOX2, and KFL4.

The team goes on to show in the paper that chemicals can do some reprogramming too. This kind of small molecule approach (alone or together with genetic factors) also already has been shown by a variety of other teams even if some of the specific chemicals are somewhat different. I’ve written extensively as early as a decade ago on chemical reprogramming of cells.

What is a teratoma? human stem cell teratoma knoepfler lab sm
Human iPS cell-derived teratoma. Knoepfler lab research image. The iPS cells here were made using OSK and MYC. I believe that OSK-mediated rejuvenation attempts could lead to teratoma even without MYC in the mix.

OSK-mediated rejuvenation?

From the abstract: “We identify six chemical cocktails, which, in less than a week and without compromising cellular identity, restore a youthful genome-wide transcript profile and reverse transcriptomic age.”

Are the terms “youthful transcript profile” and “transcriptomic age” scientifically rigorous? It depends on whom you ask. These assays of age/youthfulness on reprogrammed cells are what seem relatively new to this paper.

Is that “youthfulness” element the source of the overexuberance in the media and on social media?

More practically speaking, could “OSK-mediated rejuvenation” actually do something useful in people someday? Could a pill mimic this kind of effect safely in the future? Sinclair seems to think it’s possible.

There would be risks, which don’t seem to get attention.

Recall that even without MYC in the reprogramming mix, OSK activation could potentially do harmful things too. For example, it wouldn’t be good to have a bunch of our cells become pluripotent stem cells again.

Risks of hype and unproven anti-aging regimens

Youthful RNAs or transcriptomes (if such things even are real) might sound good, but I wouldn’t want a bunch of teratoma popping up in my body.

I’ve included an H&E stained section from a teratoma in mice generated by research in my lab years ago from human iPS cells. We generated these iPS cells with OSK (and MYC).

Though it’s a beautiful picture, you wouldn’t be happy if these were in your body due to premature anti-aging clinical trial efforts.

To me what Sinclair is pitching with the idea of reversing aging in humans in the future seems far ahead of the data. Steve Horvath and others have published some very cool data in this space on epigenetic elements but is it time already for clinical trials?

Lifespan and more claims

I’m skeptical about this and I’m not the only one.

I asked a scholar in the stem cell and reprogramming field for their opinion on Sinclair’s claims and they said:

” As a stem cell scientist, I’m insulted by his unsubstantiated claims. At best, he will lead the unaware astray; at worst, he will diminish the credibility of all of us who do serious research with stem cells.”

In a negative review of Sinclair’s anti-aging book, Lifespan: Why We Age and Why We Don’t Have tobiologist Charles Brenner ends this way:

“The reach of Lifespan is a problem for the world precisely because a Harvard scientist is telling fictitious stories about aging that go nowhere other than continuing hype”

I’m not sure the public is hearing this kind of pushback though.

David Sinclair challenged by an unlikely source

Still, even The Daily Mail, reporting on the new paper, in a sense, challenges David Sinclair on some of his claims and recent tweets:

“Other scientists, including a Harvard professor, have said the study ‘is mostly hype and preliminary’.”

This other bit of info is important:

“Sinclair is named as a co-editor on the board of the journal that published the Harvard paper, which was received on June 30, 2023, accepted on July 4 and published on July 12.”

That’s a speedy review. Rigorous? It’s possible but the way this was published is unusual.

Why does this anti-aging exuberance matter? Why be concerned?

Many people may be getting the wrong idea about where the research stands and its translational implications. Some may start taking supplements based on the hype or making other potentially risky changes to their lives. Note that Sinclair’s tweets even caught the attention of Elon Musk who amplified it just by asking about it.

Technology that does interesting stuff in cells in a plastic dish or even in mice or other lab models will not always necessarily work in people. We’ve seen that so many times in research. Murine research is important and Sinclair mentions other animal models, but the jump into clinical research is a big step.

David Sinclair supplements & supposed anti-aging regimens

There’s also some other context here.

If you search for “David Sinclair” on YouTube you can find a slew of videos on other people’s channels with him seemingly promoting many kinds of unproven anti-aging supplements and regimens. These are often clips of interviews or talks.

I believe there’s a lot of hype in these videos. Similarly, Sinclair’s book (and his own associated YouTube channel) also make many claims.

I’ve even seen people asking on the web about David Sinclair supplements as though it was a brand name. Maybe it will be? What supplements does he take? The list below is a partial one from the web and YouTube videos but I haven’t confirmed them with Sinclair and what he takes likely changes over time:

  • NMN
  • Resveratol
  • Vitamin K2
  • Vitamin D3
  • Metformin (a prescription drug for diabetics so should non-diabetics be taking it?)
  • Aspirin
  • And many more.

Yet none of these things are conclusively proven to be good for human health and fight aging or to be entirely safe for everyone.

Part of the challenge is that the neanimorphic Sinclair channels into some powerful elements of human nature related to aging and dying. Who wants to get old and die?

Looking ahead, will any of Sinclair’s various companies or perhaps future ones improve people’s lives? Extend them? I hope so but so far the data are way behind the aspirations in my view.


  1. New David Sinclair paper in Aging journal.
  2. Critical Daily Mail article.
  3. Negative review of Sinclair’s book Lifespan by a respected biologist.

7 thoughts on “Review of new David Sinclair paper, supplements & anti-aging glitz”

  1. Richard Betancourt

    Does this nullify Sinclair’s stand that aging is a disease? What of the convincing rejuvenating experiments successfully completed by Randy Jirdle on his agouti mice at Duke University? Or the 53 year-old skin patch returned to the condition it was in at age 23 – an experiment performed at the Babraham Institute two years ago?

  2. Deepa Bhartiya

    The first sentence in the Aging paper by Sinclair’s group suggests that loss of epigenetic information results in aging. So, what happens when we are young? Is it that body cells maintain a healthy epigenetic state throughout life? Does Prof Sinclair disregard any role of stem cells in regular turnover of cells in the body? This is where the problem is. Aging is better described as a loss of normal functioning of endogenous, tissue-resident, pluripotent VSELs. VSELs work in a subtle manner to maintain life-long tissue homeostasis and this function gets affected with age due to a compromised niche. Thus stem cells do not function normally and fail to replace cells to maintain homeostasis. As an example, to illustrate this, transplanting aged mouse ovaries on younger mice restores their functions (doi: 10.18632/aging.100105). We recently reported increased numbers of stem cells in an aged mouse ovary showing blocked differentiation (doi: 10.1186/s13048-022-00968-4).

    There is an alternative explanation to why Sinclair’s group observe loss of epigenetic information in aged cells. VSELs are pluripotent stem cells with abundant euchromatin and show biallelic erasure of imprinted genes. This is how they remain quiescent with double expression of H19 and minimal IGF2. Every time a VSEL undergoes asymmetrical cell division, it self-renews and gives rise to a slightly bigger progenitor which becomes tissue specific. This is a dynamic process, chromatin modelling occurs, more than 90% of chromatin gets inactivated and imprints are set resulting in monoallelic somatic imprints. As a result, progenitors divide rapidly and show clonal expansion before undergoing further differentiation. This process requires very efficient DNA methylation machinery. Defects at this stage will result in cells with altered epigenetic state with age. Similarly, loss of imprinting is observed in several cancers. Both aging and cancers occur due to stem cell dysfunctions. I will invite all to read the article (DOI: 10.1073/pnas.1100816108), kiss with death assay of Prof Trosko (DOI: 10.1002/ar.22793) and a review on VSELs by Prof Ratajczak (doi: 10.1161/CIRCRESAHA.118.314287).

    In vitro iPS was questionable and now reprogramming in vivo. Both these concepts are not acceptable. Let us together study methylation status of aged and cancerous VSELs and compare it to normal. Manipulating VSELs can cure cancer and also reverse aging. But lot needs to be done. Thanks, Paul, for this platform for discussion.

      1. VSELs exist in all adult tissues. If they do not as you suggest – please explain the ubiquitous expression of OCT-4 and FSHR on cancer cells affecting multiple organs. Uncontrolled expansion of OCT-4 and FSHR positive, pluripotent VSELs initiate cancer and this explains OCT-4 expression reported by various groups in cancer. The numbers of VSELs are so few in normal tissues – that they remain elusive.

  3. Admin,

    Let me help everyone with this issue. Years will go by, and those of us who are still alive will be able to look back and know what you and I already know, but you are for some reason too genteel in this particular case to say:

    It’s a crock.


    James @ Asymmetrex®

  4. Sinclair’s “age test” is based from what I know, purely on methylation. It seems to me that’s a myopic view and there are many other factors, working in harmony with one another, that are not accounted for. Thoughts?

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