Why Most Anti-Aging Tests Are Total Nonsense (And What Actually Works) | Dr. David Furman

We're going through the most sensitive way of estimating aging rates, and you do it by exposing cells to simulated microgravity or ground analog gravity on the ground, on Earth, so you don't have to send the cells to space. Just for context, astronauts suffer from accelerated aging. So what we have done was to take response to microgravity to accelerate the aging. So I can see that aging happening in the future, and we can map that to five years of aging. So that's the most sophisticated stuff out there.

Do you think the current testing available are worthwhile to take?

First of all, I'd like to thank you for interviewing me here. I believe that this space has evolved quite rapidly since the first epigenetic clocks that were described in 2012 with Hannum and Horvath. And we have this beautiful presentation from Steve Horvath yesterday here in Shanghai. The epigenetic tests were rapidly commercialized by different companies. And I would say probably too abruptly. And because the space is not regulated, it's very difficult to know how to judge those tests, how reliable they are, how accurate they are when you do test retest. We've seen, you know, interviews with Matt Cavelin saying it's all over the place, the epigenetic tests. And if you're stressed or something systemic happens to you, they go up by 20 years and then, you know, a few days later they go back down. So they're very sensitive to things that we still don't understand well, but not only that.

I've heard of people who are doing the test on the same day, but they put in the samples using different names and they got drastically different results.

So that is what you're calling variability that is not caused by biology is caused by technical issues. Right. These tests rely on arrays, so the probe needs to bind the CPG islands and then you have a signal. There are other tests out there that are maybe not yet commercialized, but are more reliable, that are based on transcriptomics. You basically are sequencing. You're sequencing the rna. There's less. There are. They are less prone to error, technical variability as well. Now, you asked me a question that is super important, right, for the space, because we see more and more people jumping into longevity and they want to do better and they want to optimize their health. And so what works, right? That's the key question. I think the winner will be the test that can inform interventions, that is intervenable. That's first thing. The epigenetic tests, for as much as they are very, very accurate at predicting chronological age, they're not quite yet intervenable or we know very little about how to intervene. There's a few studies now looking at different modalities of intervention. And see, for example, we published, right. The therapeutic plasma exchange paper that we talked about showing that there's a reduction of about three years of biological age, and that is using epigenetics. So, you know, if you're measuring before and after in the same individuals, you get better accuracy than if you're measuring, you know, in different individuals of the same age or the same. Now that was across 40 clocks. So when you average all the clocks, you have more reliable tools to assess improvement. But if you have the results of the epigenetic test, you don't know how to intervene. Now, on the other hand, there are other tests like inflammation, that you know how to intervene. We know how to target inflammation. And so those to me are more telling, are more important, can guide you on how to where, where to go.

The inflammation is very much tied in with aging. Right.

So, oh, 100%, 100%.

You reduce inflammation, theoretically, maybe you can reduce.

I was just interviewed by the Time PI team and one of the questions that they posed is how important treating inflammation or targeting inflammation will be for the other aging parameters or features. It is very clear. I think it's a consensus in the scientific literature that inflammation is at the center of aging hallmarks is one key predictor of most, if not all of the diseases of aging.

I see.

And so imagine you can target information, you can do a lot of savings in healthcare, and you can improve the health span of the population, you know, at large.

Yeah, yeah. So the current methylation tests, what do you think the pitfalls are in these tests?

I think the pitfalls are twofold. One is the issue of variability that we just discussed. If you have different companies, you may have very different results. That's a huge problem. That's a huge problem. What do you believe? You don't know what to believe.

Yeah. So it's just there are methods.

No, the method is the same. The thing is that there are different companies that say the operator that runs the test may introduce some bias even in the same technology, say the Illumina EPIC array. Run here and read here, you're going to get different results. So interoperability is something absolutely key for a test to be reliable, and that is basically winning the space. The second piece is how trustworthy they are. If you have a test that comes from a group that published in a obscure journal, and here comes a company and tries to License that out and market that. You know, that it's not coming from a strong scientific grounds. And if you now have Nature Aging or Nature Medicine or some other very high profile peer review journal you can trust more just by default because you have better sets of reviewers and the impact factor of that journal is substantially better.

Yeah. So you're seeing a lot of these companies out there have just utilized technology that has not really gone through enough vetting, enough tests or enough validation 100% that they just went to market.

It's the wild west in a sense that what's prevailing is not the science but the commercial interests.

Yeah.

Even some companies marketing things that have not been peer reviewed, that went out to some, you know, preprint.

Yeah.

And they're already taking the test and marketing this and trying to.

And I guess because they're not talking about treatment. So they're not under the same kind of scrutiny as, you know, as far as the FDA goes.

That goes back to the idea, Right. That the regulation in the space is not there yet and the bar is so low that you see these things happen. Right. It's not the same as in industry with pharmaceutical drugs or serious diagnostics that went through processes through the FDA and are FDA approved. You can count that those are real, that the results are reproducible because there's regulation and there's standards behind.

Yeah.

Clia, for example. CLIA testing is a standard. You need a CLIA lab to show reproducibility and reliability and accuracy and all those things.

So do you think methylation based biological age tests in theory is great and just in practice it's harder to control the variables.

That's well put. In theory. It's amazing. I mean, we've discovered and Horvath has done a tremendous job at identifying methylation variants or you know, CBD contributors to lifespan and to health span having all these predictors, which is amazing. Never ever in the past we've seen such a great level of detail now bring that to the industry. That leap is something we need to carefully vet and to carefully go through so that the test is as solid and as reliable as did the research that was done in the academia in the first place. Because all these things come from academia. So that academia to industry transition needs to happen in a very thoughtful manner. So I can give you an example. Our inflammatory age test. We produced this test in 2021. It's a nature aging paper, very solid and peer reviewed and in a really good journal. Bring that to the academia, to the industry. It took us Several years to have the level of accuracy, the level of the test retest, a small error to reduce that error to the minimum so that we produce something that's meaningful for our clients, for our patients. So now we're, you know, rolling this out four years later.

Yeah, yeah.

With a CLIA lab.

I see. So. So another new test that's emerging is from Generation Lab and they are testing the genetic noise. They were talking about how the variation in the noise is indicative of the biological function and the age. And what are your thoughts on a test?

It's a really interesting concept. Quite novel in that Schumacher, a few years ago published a paper, Nature Aging as well, where you can create a clock based on random stochastic noise. He came up with the idea in the first place. And then it was Vadim also contributed to some of that work in the literature. And so Generation Labs are basically using this natural biological noise to estimate what's important. Whether or not this will be reliable and specific enough for different functions we have yet to see. I think I presented a clear example where if you look at epigenetic age systemically and you're not accelerated, you're not decelerated, you're right on your age. You're kind of okay, you believe I'm fine. You know, I can go on. Turns out that your heart is accelerating, right?

Yeah.

And your liver is decelerated. And so the net will be zero.

Right. But one good thing about their test, that they are testing, I think 19 different organs.

Yes, yes. So that level of accuracy adds to. Or that level of specificity adds to and tells, you know, tells a good story. It tells us a very good story. Now we have to see how that can be commercialized. And when I mean commercialized, I mean productized in a way that we can trust the results, the test retest accuracy, the error is the lowest possible. That everything is done in a clear environment to give our customers and our public in general something that's meaningful. We. Right. Because if I test myself today and I test myself tomorrow, and yet I did nothing, I would expect that the results are almost the same.

Yeah, yeah. I think that's a frustration in anti aging doctors. If you are trying to base your treatment plan on your test results and the test is all over the place and you don't know, you know, it should be working. But why is the result telling you something different? That's right. It blew up your whole plan.

Very frustrating. Not only for doctors, for the public in general. And that creates a very bad optics.

Yeah.

For what we're trying to do, we're trying to build credibility. We're trying to build a case for measuring aging rates.

Right.

And if people don't believe, you know, it's the end of the story. So that's I think very bad practice to come with an unfinished test and bring it to the market. Because there's deception and people won't believe in what we can offer.

Yeah, yeah. And of course you are really important researcher and head of your sector for aging studies in, at the Buck Institute, which is the, the premier aging study institute, the first one in the world. Is that correct?

Is the largest institute focused solely on aging.

Yeah.

In the world.

Yeah.

300 researchers.

Wow.

25 faculty members. Solely focus on mechanisms of aging interventions, diagnostics. Solely aging.

Right.

Yeah.

So. And you have a big team as well. So you are definitely an authority that I can get some good answers from. So if I ask you, what are you the most excited about in anti aging age testing? In biological age testing?

Yeah.

What?

Well, makes you clear. Yeah, yeah, yeah. My, my, my interest at the moment and the vision is to be able to democratize everything, to make it available to every one individual in this planet. To try to bring things to the masses, to bring the cost down. I've been developing tools that, that simply with a selfie, Right. I call that healthy selfie. You can measure inflammation in the body. It has certain level of error in the measurement. So it's not as accurate as a blood test, but it tells you where you're at and what are the potential causes of it if you have that paired with a, say, exposum survey. And so we can make this ultra low cost technology available to Everybody. There's around 4.5 billion users of smartphones in this world. So it's essentially free for all. So that, that's, that's I think what needs to happen and what's coming.

Right. And you let me test it and it's very fast and easy.

Right. You take a picture, take a picture.

A couple things in there and then.

You get your estimated biological age or inflammatory age if you're accelerated or you're okay.

Yeah. And I want to borrow Dave Pascal's, he's, he's analogy. He said, you know, a test like this probably is not. It's like when you have a GPS system, it's not going to tell you if you're in Beijing or Tianjin, you know, but it will tell you it's in China.

Exactly. I love it. I love that analogy. It is for most cases, good enough.

Yeah, but then you have a more accurate test that you're working on.

Correct. We're going from that to the most sensitive way of estimating aging rates. And you do it by exposing cells to simulated microgravity or ground analogs of gravity on the ground on Earth, so you don't have to send the cells to space. Just for context. Astronauts suffer from accelerated aging. So what we have done was to pivot on this response to microgravity to accelerate the aging. So I can see that aging happening in the future, and we can map that to five years of aging. So say you take your cells, put in a microgravity. I have two time points, I have the baseline where basically cultured YOLO cells in. In one G, which is this gravitational forces. And I put the microgravity that gives me a trajectory of aging. That's the most sophisticated stuff out there. It's an expensive test.

Is it?

It's $2,000.

Oh, gosh.

So there's no way we can bring. It's difficult to bring the cost down because we have to move the cells around and bring them and culturing them and putting microgravity. It's a lot of preparation, specialized equ. Specialized personnel. It's not like these epigenetic tests that you can put your fingerprint or your cheek swab and you have an answer by running it through a machine. You need a whole lot of preparation.

I see. So what does this accelerated aging test tell you?

It tells you how you will be affected by hallmarks of aging in a five year time. So I may age through inflammation more than you? You may age through cell cells, cell senescence or issues with mitochondria or your microbiome. This is what it's going to tell you. Oh.

So pinpoint the cause.

Your hallmark of aging that will be accelerated from here to the next three to five years. It's not specific, but it's giving you that aging rate. So now you can map that to supplements, foods, exercise, recommendations that are tailored for that aging rate.

Oh, I love doesn't just tell you that it's aging or there's methylation issues, but it tells you the mechanisms of.

Exactly the hallmarks to that place. Yep. Yep.

Okay. Yeah. So how many mechanisms can it identify?

You said 12 hallmarks of aging. All those are drivers, but we also have two that are protectors. So during aging, there is the aging itself or mechanisms that happen and accelerate aging. Inflammation is the classical example that we discussed prior. But there's also protective mechanisms that increase with aging. Right. For example, Autophagy, that's a protective mechanism. Resilience, that's intrinsic capacity. You want to maintain intrinsic capacity. All those are protective mechanisms. So in total, we have 14 pillars, 12 aging drivers and two aging protectors.

I see. So the drivers, you mentioned two of them, but there's a range. Can you name a few other ones?

So the drivers are cell, cell communication loss and you have stem cell exhaustion and you have. All these are terms that the public may not understand. But we now have this framework that everybody in this space of aging and longevity understands.

Yeah.

Which is These are the 12 hallmarks of aging that happen as a mechanism to age ourselves and our body. Inflammation, cell cell communication issues, mitochondrial dysfunction, microbiome or dysbiosis, Autophagy, alteration in autophagy that I mentioned before. And there's a number of others that I can list.

So your test can actually see which part of the problem is.

Exactly.

That's amazing. Yeah, that's tremendous tool for doctors.

I believe it is. I believe it is because it pinpoints the mechanism and it gives you solutions to you how can change that trajectory.

Okay. Yeah. So how mature is this technology?

How much?

How mature?

Oh, how mature?

It's $2,000.

It's mature enough to go to market. We're launching next month.

Oh, my God.

I'm going to, I'm going to send you an invitation. This is invitation only. And we're rolling this up out through clinics, concierge medicine doctors and, you know, healthcare providers in the space of longevity. This is not going to be a direct to consumer, not until the end of this year for a variety of reasons. But it's. The technology is mature enough. But we are not seeking direct to consumer yet because there are certain challenges to make this test CLIA approved. And the CLIA regulation that I mentioned before in the clinical testing, the CLIA regulation for things like cell culture, and you're incorporating the simulated microgravity. And so our examiners will say, how can I cope with all this very fancy state of the art technology? Therefore, this is going to be an IRB approved study. It's a paid study that anyone can sign up for through the clinics. Because getting clear for these very sophisticated things is going to be challenging.

Okay. And this is through a blood sample.

This is through a blood sample that can give me enough cells to do all the experiments that we need to do. So it's actually a lot of blood. It's 30 and 40 milliliters. So not a tassel device. So definitely not. Not something like, you know, you Prick your finger.

The doctor needs to draw it. Maybe you develop something that's. You need.

No, because you need the cells to be in microgravity. You need a lot of cells.

Yeah.

And in order to get enough cells from our patients and clients, you need around 40, 30 to 40 milliliters of. Of whole blood.

Yeah, that's a thick tube of it.

These are four tubes.

Yeah, four tubes.

You know, vacu tightener tubes.

Right? Yeah. Okay. Yeah, that's. That's awesome. Congratulations.

Thank you.

Yeah. I look forward to testing out your technology.

Send your cells to space.

Oh, amazing. I have a. I. I don't think I'm gutsy enough to actually go to space, so I'll do a proxy here.

Exactly. We don't want to go to space. You're going to age, so might as well just take the space cells, see how you will respond to that aging stressor, and, you know, create solutions for it.

Amazing. Thank you so much for sharing your wisdom and, and thank you for your pioneering work. And, and I see your, you know, you wonderful team and you. You take your team out to enjoy life at the same time advancing science. So, yeah. Seeing everybody right. In good health, good spirit.

Absolutely.

While you're doing good in the world.

Thank you so much for inviting.

Really appreciate you.