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Chris Mirabile on the NOVOS Approach

We discussed biological aging tests and supplement efficacy.

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With multiple experts on its scientific advisory board, NOVOS offers supplements containing ingredients that recent research has linked to longevity. This company also markets biological age tests for people who want to monitor their progress. We spoke with NOVOS founder and CEO Chris Mirabile about the company’s ideology and approach.

Please explain the science behind your two supplements. Why do you think it is not too early to market “longevity products,” given the current state of research?

NOVOS is a consumer longevity platform that provides three key solutions: formulations in the form of over-the-counter, patent-pending longevity supplements; tests, both best-in-class biological aging clocks and free online assessments; and longevity health guidance in the form of free science-based knowledge.

To your question specifically about our supplements, NOVOS Core and Boost, we determined that the time was right to bring these products to market based on the current state of longevity research and our own research efforts.

We know a lot more about aging today than we did even just a few years ago. We’ve successfully reversed biological aging, we’ve extended the lifespans of many animal species, and we’ve epigenetically rejuvenated animals – and we understand the biological pathways and mechanisms through which these approaches work.

To that point, NOVOS is the first longevity company to approach aging from the context of the established biological mechanisms of aging with a goal of impacting ten or more simultaneously. That approach is what many longevity scientists agree will be the most likely to make an impact on healthspan and lifespan.

We have a lot of supporting research and data that continues to grow in support of our formulations and the ways in which they can impact aging.

How did you arrive at the specific formulations? What is unique about your approach?

Beyond being the first to address aging from the context of many hallmarks of aging simultaneously, we took a meticulous approach to the formulation of our foundational product, NOVOS Core. First, we ran natural ingredients through a set of ten filters. Specifically:

  1. They have to have the ability to impact aging mechanisms, such as epigenetic dysregulation, cellular senescence, and mitochondrial dysfunction.
  2. Ideally, each ingredient favorably impacts more than one of the mechanisms at a time.
  3. They have to have been able to extend lifespan in various animal models, hinting that the biological pathways are evolutionarily conserved in humans.
  4. They are associated with reduced risks of different aging-related processes, indicating that they likely act on underlying aging processes.
  5. They are associated with reduced risk of mortality in humans.
  6. They are recognized as safe by FDA, EFSA, and other health organizations.
  7. They are nature-based.
  8. In many cases, they are found in the human body but their levels decrease with age.
  9. They have a very low to no side effect profile.
  10. They have been used for many decades, or even centuries, to treat specific symptoms or afflictions in humans without serious side effects.

After conducting the research to arrive at our short list of potential ingredients for the formulation, we then considered synergies and potential dysergies, along with short-term effects, and dug deeper into researching each ingredient. We arrived at more than 190 scientific studies that supported the inclusion of our final formulas’ ingredients from the context of longevity and many more than that from the context of general health.

We then created a prototype formulation and administered it to dozens of beta testers, who noted any short-term benefits and side effects. With virtually no side effects and multiple short-term benefits being reported, ranging from improvements in skin, mood, sleep, energy, and cognition, we determined we were ready to move on to scientific tests.

We started with in vitro human tests, investigating the impact of NOVOS Core and Boost on specific mechanisms of aging. In one study of DNA damage, we found that the combined effect of Core and Boost reduced DNA damage to human umbilical vein endothelial cells from irradiation by up to 77% and, on average, 68%. These numbers were the best that the lab had ever seen, despite doing millions of dollars’ worth of similar studies on natural and prescription compounds prior to NOVOS.

We also ran a study on NOVOS’ impact on senescent cells with Professor Von Zglinicki, Professor of Cell Gerontology at Newcastle University. His lab found that NOVOS Core and Boost demonstrated a senostatic effect on senescent cells, decreasing their size by an order of magnitude comparable to the gold standard prescription longevity drug, rapamycin.

In another study (that we have not yet published because the research is ongoing), we found very promising effects from NOVOS’ impact on human DNA single- and double-strand breaks from the administration of chemotherapeutics.

We also tested NOVOS Core and Boost on a small group of people and measured skin health parameters using an indentometer. After six months, all subjects had improvements in their skin suppleness and firmness, with a minimum improvement of 12%, a maximum of 40%, and an average of 22%.

In a human case study of NOVOS’ formulations that we have not yet published, zero participants had accelerated biological aging after six months of use, as measured by the PCDunedinPACE clock. 74% had statistically significant decreases in their pace of aging, with a p-value of 0.001.

We’re not stopping here. Multiple additional studies are underway to further prove NOVOS’ real impact on longevity and signs of aging.

What makes your supplements “anti-aging” rather than just “pro-health”?

NOVOS solutions are pro-health, but they do so much more in their ability to slow down aging. The research behind our ingredients’ abilities to extend lifespan in many species is backed up by our third-party research studies indicating our ability to impact fundamental causes of aging, the growing evidence for our ability to favorably impact epigenetic biological age clocks, and real-world customer testimonials ranging from epigenetic test results to improved health markers that are correlated to aging.

While every ingredient in itself has some scientific evidence behind it, how can we be sure there are no unwanted interactions between them?

We started by thoroughly researching each of the ingredients to fully understand the biological pathways through which they function, eliminated all ingredients from the consideration that presented possible dysergies, administered beta tests of the formulation, and have been following up with a wide range of scientific studies and collecting feedback from a very large customer base. There is no evidence of negative interactions between our ingredients. Safety and efficacy are paramount for NOVOS in all of our solutions.

NNM is known to have oral delivery issues. How do you deal with that?

NMN research uses regular, powdered NMN – not sublingual and not liposomal. From these studies, we can arrive at dosages that demonstrate favorable health outcomes, regardless of what percentage of that oral dosage is absorbed. That is ultimately what’s important to know. That dosage, where benefits are perceived, is 250 mg. Some, like Dr. David Sinclair, may go as far as 1 gram with their NMN dosages. NOVOS Boost enables you to easily reach either of these dosages and everything in between.

We have several issues with liposomal delivery of NMN. First, the amount that is absorbed is likely significantly higher than regular NMN. This may sound good at first, but if 250 mg of liposomal NMN provides 6x (1.5 g) or 10x (2.5 g) greater absorption, there may be negative effects that accumulate at dosages that high. Remember, studies demonstrating benefits are at much lower dosages and with regular NMN.

Next, liposomal delivery does not only mean greater uptake into the bloodstream. It also means greater absorption at a cellular level. This is typically touted by brands as positive, and at first, this may sound good, but it is not necessarily so. The human body is very smart in determining how much of a specific molecule it wants to absorb, all the way down to the organ and cell. This homeostatic process is disrupted with liposomes. In other words, cells that may not ordinarily absorb the NMN will be forced to do so, as well as cells that would otherwise absorb less now have more. We all know the adage “the dose makes the poison”; NMN is no exception to the U-shaped dose-response curve.

It’s often tempting to go with the “high-tech” solution or something that sounds better at first because of absorption characteristics, but when it comes to biology, it’s not that simple. At NOVOS, we first want to do no harm, and as such, we are basing our NMN form factor and dosage on the published research and associated safety, not on a simplistic perspective of “more is better.”

Among other things, NOVOS Core is supposed to help slow skin aging. How does it square against established skin treatments?

NOVOS Core, a powdered drink mix of 12 longevity ingredients, includes ingredients that have been found to not only contribute to longevity but to also have short-term skin health benefits.

For example, oral hyaluronic acid was added to the formulation not for the reason you might think. It’s not the hyaluronic acid itself, but a component of it: acetyl-glucosamine (do not confuse it with glucosamine sulfate, another ingredient in Core). Acetyl-glucosamine is a substance that extends the lifespan in organisms and can reduce protein accumulation, one of the drivers of the aging process.

An added benefit of hyaluronic acid is that the oral form of it increases the amount of HA in the skin, which is a building block of skin and declines up to 75% in the elderly versus the young. Hyaluronic acid improves skin suppleness, moisture, and radiance and even improves joint health.

Another ingredient in NOVOS Core is glycine, an amino acid that can reduce the formation of advanced glycation end products (AGEs), which make tissues like the skin and blood vessels stiffer, improves mitochondrial function, reduces inflammation, and extends lifespan in various organisms. It’s also a fundamental building block of skin collagen.

Other ingredients, like glucosamine sulfate and calcium alpha-ketoglutarate, have both longevity benefits and simultaneously improve skin health.

Now, to your question: established skin treatments are typically topical serums and creams that moisturize the upper layers of the skin. These products are great for improving the visual appearance of the skin acutely – that is, you look in the mirror, and your skin is looking more hydrated and radiant. However, when it comes to skin aging and improving the skin from the inside out, these products fail to deliver.

NOVOS Core takes the approach of, first and foremost, impacting the aging process of your skin (and overall body) to keep it younger for longer, while also delivering short term improvements in skin firmness, hydration, and radiance from the inside, after one to three months of consistent use. We strongly believe that if you take Core and years from now compare yourself to your friends who didn’t, your skin will have aged less, assuming no major confounding factors on your part like sun exposure without sunblock, smoking, or poor diet.

You have launched NOVOS Age, a kit to measure the pace of biological aging rather than biological age per se. Please explain the value of this approach and of the chosen clock, DunedinPACE.

We look at biological age clocks and aging as being roughly analogous to scales and weight loss. If you can’t measure something, you can only guess how well you’re doing. We want to empower our customers to track their progress during their NOVOS Longevity Journey, and we are confident in the impact that we can make.

To do so, we wanted to make sure we equipped our customers with the most powerful epigenetic test currently available. Being a third-generation test (the latest version available), as opposed to most other clocks being only first- and second-generation, and created by Columbia University and Duke University researchers who utilize decades worth of dozens of relevant aging and health markers from the same cohort of more than 1,000 people, DunedinPACE is widely considered to be the most powerful and accurate test available on the market.

To that point, we performed an internal analysis of all of the popular epigenetic tests out there and found that DunedinPACE outperformed them all, particularly when it came to accuracy for an individual testing and retesting, as opposed to a scientific study in which you are testing a population of people, so inaccuracies average themselves out.

We also like how DunedinPACE measures your current rate of aging, which changes more rapidly than biological age and is what you ultimately have control over with your daily lifestyle decisions.

To your point about biological age, we do also offer that as part of the NOVOS Age package because people are curious – but I can tell you, it’s not nearly as accurate as DunedinPACE and should not be focused on to judge the success of your longevity lifestyle approach.

The kit also measures telomere length. What is the added value of this?

Telomeres are the endcaps of our chromosomes that protect our DNA, and they decrease in length as we age. Once thought to be a great indicator of biological age, researchers have since determined them to be too highly variable across age to be relied upon for that purpose. Nonetheless, when telomeres become too short, the risk for multiple diseases, especially digestive tract cancers, go up.

We decided to include this report in NOVOS Age, alongside DunedinPACE and biological age, because it’s a relevant data point for aging, and it’s something that you can influence: its rate of attrition, or even adding to its length over time with lifestyle decisions.

With the longevity field being relatively new and unknown to the general public, longevity biotechs have to invest in education. How do you approach this task?

Many people, even those within the longevity community, are unsure where to draw the line between general health and longevity. So, we have a long way to go to simplify the messaging, educate people, and clarify the relevance to each person’s life, which is far more powerful and impactful than the more short-term focused health advice that most people focus on.

As a Public Benefit Corporation (PBC), NOVOS contributes a significant portion of its resources towards creating free educational content. We publish Ph.D. and MD-authored content on our blog; host free webinars about longevity lifestyle guidance, technologies, tests, supplements, and more. We also donate to charities and researchers that are furthering the effort.

Your scientific advisory board looks very impressive, can you tell us a little about them and how they are helping you with the science?

NOVOS’ Scientific Advisory Board (SAB) and scientific consultants are composed of six longevity PhDs from Harvard Medical School, MIT, and the Salk Institute.

Specifically, they include Dr. George Church, Dr. J. Pedro de Magalhães, Dr. Pamela Maher, Dr. Oliver Medvedik, Dr. Avi Rosenbaum, and Dr. Matt Kaeberlein.

These scientists have assisted us with the NOVOS Core formulation process, including providing insights into ingredients that may not be printed in papers but are known from unpublished experimental data; scientific study design; guidance on longevity-relevant technologies and tests; and even website content advice. Our SAB is very generous with their time and are present when we need them for some of NOVOS’ most important decisions.

It’s also worth noting that there are more than a dozen other scientists in the field that we are regularly in touch with for knowledge, guidance, and studies, whose names we don’t publish on our website but are also advising us.

You mentioned that NOVOS is a Public Benefit Corporation. What is this status, and why was NOVOS recognized as one?

NOVOS was founded as a Public Benefit Corporation. As such, NOVOS’ founding documents have an expressed purpose statement setting forth the public benefit that we will pursue. To that point, we owe it to the community to produce products that are grounded in legitimate science and that we believe will significantly add towards our longevity vision of contributing more than a billion years of healthy life to humanity.

It also means that we will provide free resources to the general public, regardless of whether or not they are customers. We are currently doing so by publishing free educational content, offering a free age test (survey) based on scientific research that will give you an idea of your lifespan potential and guidance on how you can do better, and offering a free FaceAge test, which uses AI to measure your perceived facial age and skin health markers. We also donate a portion of our profits to longevity research.

Tell us about your plans and NOVOS’ vision for the future.

NOVOS is fundamentally set up to keep on top of the latest longevity research and to transfer that directly to the consumer in a safe, accountable way. This means that we won’t always be the first ones selling a hot new ingredient, but will instead focus on safety and efficacy research, and adequate scientific advisory guidance towards offering that ingredient or formulation to the public.

This is what we did for epigenetic tests, spending more than 18 months researching, experimenting, and running analyses on our options before bringing NOVOS Age to market.

We will continue to approach the issue of aging in a more sophisticated way than other consumer companies, which means thorough research, experimentation, and solicitation of advice from world-renowned experts who know more on the subject matter than what is publicly accessible via scientific journals.

We hope that this approach will engender trust with consumers, as they come to realize we’re not about rapidly launching as many products as possible to make a quick buck, or presenting overly simplistic analysis of products and their purported benefits to win a sale. We are in the longevity space for the long term to make a real and favorable impact on our own healthspans and lifespans and that of our loved ones and humanity at large.

So, keep an eye on us because we have a lot of exciting innovations in consumer longevity to come!

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