Neurohacker Collective has just released a product called Eternus, a 38 ingredient supplement that aims to address all key factors of aging at the cellular level. I have not tried it, and can't speak to its effectiveness (so please don't take this post to be an infomercial or endorsement), but I am definitely curious about the longevity space and whether such a product in conjunction with healthy eating and regular exercise could be effective.

Also, I personally know the folks at Neurohacker and find them to be very thoughtful and caring about what they put into their products. A few years back, I contacted Neurohacker because I was curious about their product Qualia, which incorporates a large number of different nootropics. Qualia is designed to target the whole system and bring about "radical cognitive enhancement."Of course I was skeptical. But I was also curious, and my interest piqued even more when I saw that a psychologist I respected was quoted on their website with a favorable review.

So I tried it. Personally speaking (and of course I can't speak for the experiences of others), when I took it, I felt as though I could focus for a longer stretch of time, hold more in my working memory, and connect lots of dots at once. Also, my thoughts felt as though they were flowing faster, there was a lifting of my brain fog, and my anxiety was basically non-existent for the entire day. However, I don't know which ingredients in particular were having the most effect (I mean, how do I know it wasn't just the caffeine content!), and I am a bit concerned about taking so many nootropics at once. Also, I'm concerned about the long-term effects of taking the product regularly. Nevertheless, I like how much the scientists at Neurohacker researched the interactions between the ingredients, and at least tried their best to take a complex systems science approach to the formulation of all of their products. Also, they are continually updating their products, attempting to really hone in on the most essential and important interactions.*

Now, the Neurohacker Collective have entered the longevity space. Aging is a funny thing. Our susceptibility to most health ailments increase because of it. Billions are spent on cosmetics trying to mask it. Its symptoms- lower energy, poorer sleep quality, sagging skin, cognitive decline, weaker muscles- all take their toll on our lifestyle options and our self-image. We can't live forever, but we can live long, and we can live well. How long and how well depend on whether we're trying to merely manage these symptoms, or whether we're addressing aging where it begins- at the cellular level.

The Neurohacker Collective claims that their new product Eternus is "the most comprehensive cellular energy and aging formula ever designed." That's a big claim, and of course I remain skeptical about its long-term effectiveness. After all, we need rigorous scientific longitudinal studies to know. I mean, can this comprehensive approach really "revolutionize how we delay the onset of negative aging symptoms?" (See this article for a critical take from fifty-one scientists about "anti-aging" products).

But I decided to hear them out. I sat down with part of the Eternus formulation team, Dr. Gregorgy Kelly (a "naturopathic physician") for a deeper dive into aging: what it is, what occurs on the cellular level that progresses the cascade of its symptoms, and how a product like Eternus could revolutionize our approach to aging by solving for age-related decline at the most foundational level. I'd love to hear your own thoughts as well, so please do weigh in.

1. What is a complex systems approach and why do you utilize that approach to promote a longer healthspan and healthier aging process overall?

A complex systems approach is a way of thinking about scientific information. It focuses on what’s done and how a system responds over time to what was done. We believe, it’s this latter element-- learning and adaptation-- that’s most important to health; it’s also what tends to be largely overlooked.

A complex systems approach also recognizes that the whole can be something more than the sum of its isolated parts. The interactions and relationships between things matter. We have mitochondrial and cellular networks. These networks help us adapt to our diet, lifestyle and environments in ways that either help us stay healthy or age poorly. While it’s important to understand how things work in isolation; it’s much more important to understand relationships and how whole systems respond.

Neurohacker Collective uses a complex systems approach because we believe it is the best way to understand scientific information and apply it to real world problems, like healthy aging or brain performance.

2. What is the “healthy aging puzzle”?

Neurohacker Collective uses the idea of a “healthy aging puzzle” as a way to fit together what are often treated as isolated pieces of cellular and mitochondrial function into a bigger picture of how these things work together. Mitochondrial networks produce about our body weight of cellular energy (i.e., ATP) every day. Cells use this energy to do the work they need to clean up damage and do many other important jobs. A molecule called NAD+ is used to make ATP; it’s also used to activate sirtuins (a cellular stress sensing pathway) and to promote DNA repair. The food we eat is converted into ATP by several linked pathways. Hormones tell groups of cells how to respond together. Our body clock influences what cellular and mitochondrial processes are given preference at different times of the day and night. Health doesn’t happen because of any of these pieces in isolation; it’s a result of all of them happening together.

3. When adjusting for the large decrease in infant mortality and the impact of infectious diseases, human life expectancy in the industrialized world has improved quite minimally in the last century, despite so many medical breakthroughs. Why has average human life expectancy remained so difficult to meaningfully extend?

When thinking about the topic of life expectancy, it’s important to consider what it is at birth … and what it is at different points of age. Infant mortality, infectious diseases and poverty, as examples, have outsized impacts. When these types of things are accounted for, the life expectancy hasn’t changed as much as we’d expect over time. As an example, a male English noble from the 1500’s who reached the age of 21 had a life expectancy of 71, which is shorter than today, but not nearly what we’d intuitively expect.

After about age 30, chances of dying roughly double every eight years. This is fairly standard for human populations, no matter where you’re from or where you live. One reason we’ve seen relatively little progress in this number is that longevity hasn’t been a major area of medical interest or research until recently. Height and weight might be a useful analogy for why this has been the case. We might be dissatisfied with both, but wouldn’t put efforts into changing height, yet do a lot to try and improve weight. This has to do with how changeable we think they are. Until recently medicine has thought about how long we live as being more like height. This has been shifting; it’s now being thought about as being more like weight … something we can influence.

Another reason has to do with when we start to do things to try and impact it. Healthy behaviors have been one of the main ways to move the life expectancy needle. Even more important is the impact they have on the number of healthy life years (i.e., health expectancy), which was about 63 as of 2015, so quite a bit lower than life expectancy. But using behaviors to impact these is a long-term game … one that pays dividends decades after the investment in the behaviors. Many of us change our behaviors only after they’ve led to problems. This is the wrong approach if we want to live longer, healthier lives.

4. There are animals like the mayfly which barely live 24 hours, while there are shark species that live hundreds of years, and plant species like the bristlecone pine that live thousands of years. Since “aging” varies so much creature to creature, time seems to have only a very loose relationship with the “cause” of aging. What is an intelligent way for someone to actually understand what aging is?

We have a chronological age--the number of years we’ve been alive. Time is the only thing that matters for this. We also have a biological age, which is a way of describing how old someone seems to be when certain biological markers of aging are measured. Our biological age can be older, the same as, or younger than our chronological age. And it seems to be a much better predictor of healthy aging and lifespan. Biological age is important because aging is an ongoing process that starts with our cells. As cells age, they develop hallmarks of aging. These are characteristics that are related to cells looking and acting old. By this I mean they are the cellular equivalent of gray hair, sagging skin, etc. A good way to think about aging is to focus less on time, and more on these hallmarks of aging. This is also the path to impacting aging, because there’s nothing we can do about time, but scientists are discovering things that can impact the hallmarks of aging.

5. If aging begins at the cellular level, what are discoveries and breakthroughs of late which you think indicate we are at the dawn of achieving longer, healthier lives?

One of the hallmarks of aging is called cellular senescence. As we age there’s an increase in the number of senescent cells … these are sometimes called zombie cells because they haven’t been repaired into functional cells but haven’t been eliminated either. One of the recent breakthroughs was identifying the combination of a drug called dasatinib and a flavonoid nutraceutical ingredient called quercetin as a way to potentially eliminate senescent cells. My guess is that the category of compounds called senolytics will continue to be one of the near-term areas of breakthroughs, because it’s getting attention from a drug development perspective. Two other drugs--metformin and rapamycin--have shown promise in animal research. Boosting a molecule called NAD+, which can be done with nutrients that have vitamin B3 activity, is also getting a lot of attention, because the amount of this molecule decreases as we age, and increasing it has positively impacted aspects of several hallmarks of aging in animals.

6. What is Eternus? What was it designed to do?

Neurohacker Collective developed Eternus as a way to comprehensively support the molecules, pathways and processes cells and mitochondria use to make energy. The idea being that when our cells have more energy, they can do more work and get to the jobs that help keep us healthy and biologically younger. Two of the molecules at the heart of cellular energy production are ATP and NAD+. Our mitochondria convert food we eat into ATP and use NAD+ in this process. Nutrient sensing pathways like AMPK and sirtuins turn on and off genes that tell our cells and mitochondria what to do. At a more whole body level, hormones like insulin and thyroid tell all the cells in our tissues what they should be doing. And our body clock tells them when to do it. Eternus was designed to give nutritional support to promote all of these areas.

7. Tell us how a product like Eternus takes advantage of this new wave of understanding in terms of maintaining health at the cellular level as we age.

A lot of what science understands about healthier aging has come from research on calorie restriction and exercise. Both of these behaviors slow the rate of biological aging. When we were developing Eternus, we looked at the pathways and processes that are upregulated and downregulated with calorie restriction and exercise. A big emphasis was understanding what nutritional support could then produce similar responses. In a sense, Eternus was developed to mimic much of what calorie restriction and exercise do at a cellular level.

8. Give us a 101 education on the concept of “cellular energy”. What is occurring at the cellular energy is being optimized? What is occurring when it is in a state of decline?

Cellular energy is really about the linked processes that help convert the energy in the food we eat and the oxygen in the air we breathe into ATP. At a cellular level, this means we have to be able to get sugars and fats into cells. Then we need to optimize the linked metabolic processes that break them down, converting them into ATP in the process. And, we need to produce a fitter mitochondrial network, in essence increasing the capacity to convert more food into energy. As we age, these processes become less efficient. The result of this poorer ability for cells to produce energy is what we might think of as feeling and looking old.

9. Supplementation is only one element of addressing the aging process, but is it interrelated to the other factors such as sleep and exercise? In other words, what ways can supplementation with a product like Eternus increase the ease with which better sleep and exercise patterns can be achieved?

When we were designing Eternus, our hypothesis was that if we supported the capacity for cells and mitochondria to produce more energy and do more work, this should translate into improvement in areas that are often the Achilles heels of aging. We need good sleep for repair and rejuvenation. But sleep problems increase as we age. Exercise is important for preventing the loss of muscle tissue, aerobic capacity and balance that typically accompanies the passing of time. But we seem to get less from the time we spend exercising as we age. And it can be harder to start, nevermind finish an exercise session as the years pass by. When Neurohacker Collective speaks about a complexity science approach, one of the things we focus on and measure is how, on a more whole body level, people respond, especially in areas that are essential for promoting better health and performance. In our initial testing of Eternus, we found that about 4 out of 10 noticed a positive difference in their workouts. Almost one out of three people noticed an improvement in their sleep.

10. You’ve stated that Eternus is designed to take advantage of synergies between its 38 ingredients to result in benefits far larger than taking the ingredients separately could do. Walk us through an example of one such synergistic relationship between ingredients in the formula.

We think a great example is building the NAD+ molecule. Cells can make NAD+ in three different ways. While we see a great deal of emphasis on making it via one way (called the salvage pathway), the other two aren’t getting any attention. This is important because redundancy is a hallmark of complex systems. Self-regulated processes often have more than one way to do things or get what they want. Living systems use a special type of redundancy called degeneracy. This is seen in gene networks, neural networks, and mitochondrial networks. It’s the ability of things that are structurally different to perform the same function or yield the same output. Making NAD+ is an example of degeneracy. There’s a reason our cells developed this type of redundancy. Neurohacker Collective thinks it’s important to support it.

Continuing with NAD+, one of the things you’ll hear is that it’s important because mitochondria need it to make ATP. But you almost never hear that we also need ATP to make NAD+. So rather than focus only on building NAD+, Neurohacker Collective thinks we should be supporting both the capacity to produce NAD+ and ATP.

11. A term heard a lot in supplementation is “bioavailability”. What is occurring when an ingredient “increases the bioavailability” of other ingredients? And what are ingredients in the Eternus formula that serve that purpose?

Bioavailability is the idea of getting something from the pill or capsule to the places in the body where it’s most needed. Some things can be broken down as they pass from the mouth through the stomach and intestines, so the whole molecule doesn’t survive digestion. Others might be poorly absorbed. And others might be metabolized by the liver ...being changed and partly eliminated before they can get to other tissues. For some ingredients aspects of all three can occur. If the goal is to have activity somewhere in the body other than the digestive system and/or liver, it’s important to make sure more of the nutrient can get past these two hurdles. In some cases one nutrient will do this for another. An example is the flavonoid apigenin, which is found in vegetables like celery and parsley, and in chamomile tea. It has relatively poor bioavailability on its own, but this is increased significantly when combined with a compound called resveratrol found in red wine.

12. What do you think is the ingredient or nutrient that is most deficient in the Western diet with regards to aging well? What role does it play that is critically important?

Rather than a single ingredient or nutrient, I’d go with the category of plant compounds called polyphenols. These are the compounds that give many of the colors to fruits, vegetables, nuts, chocolate, coffee, and tea. It's thought that our ancestors consumed a higher amount and diversity of polyphenols than we do today. Scientists have found that diets higher in polyphenols are linked to healthier aging and increased longevity. They are also finding that polyphenols turn on and off genes, and directly and indirectly impact many hallmarks of aging.

13. What are substances, trends, or approaches regarding aging that you feel are overhyped right now? And why?

At Neurohacker Collective we think boosting NAD+ with the newer niacin equivalents called nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) would fall into this category. The fact that older niacin equivalents ... niacin, niacinamide and tryptophan ... also boost NAD+ seems to be getting overlooked or forgotten. And we don’t think boosting NAD+ by giving large amounts of niacin equivalents as an isolated strategy is likely to produce the results that are being promoted. While we think boosting NAD+ is important, it’s one piece of the overall puzzle. We’d like to see more attention being paid to some of the other pieces.

14. What are sirtuin enzymes, and what role do they play in aging?

Sirtuins are products of our genes. They are important because they turn on and off many other genes, especially genes that determine how cells respond to stress. So in a sense, they act a bit like a master regulator, dictating how many of our genes express themselves. Sirtuins play an especially important role in coordinating how cells adapt to nutritional status (including calorie restriction or fasting), exercise, stress, toxicity, and other environmental challenges. In general, increasing the expression and activity of sirtuins promotes the cellular and mitochondrial processes needed for both healthier aging and longevity.

15. What is the role of mitochondria in aging?

Mitochondrial are typically thought of as being akin to the powerhouses of cells, because they convert food and oxygen into cellular energy (i.e., ATP). Inside an individual cell there can we hundreds to thousands of mitochondria, so a good way to think of them is that we have mitochondrial networks. The health of this network will to a large degree determine the health of a cell and ultimately the tissues and organs cells are in. As we age, mitochondrial networks become damaged and don’t perform as well, which has led to mitochondrial dysfunction being one of the nine hallmarks of aging. Two of the behaviors that have the biggest impact on healthy aging are calorie restriction and exercise. Both of these work, in part, by creating fitter mitochondrial networks, which are able to produce more ATP.

16. What would you say are the top 5 aspects of our physiology we can significantly alter with proper supplementation, which may result in a better aging process?

Thinking in terms of the hallmarks of aging, and things we can start doing right now, I’d say the following 5 things: We can (1) boost NAD+ using niacin equivalents and make the NAD+ metabolome--the pathways and molecules that make and are made from NAD+-perform more efficiently by consuming certain polyphenols, (2) produce more ATP by taking nutrients that support better mitochondria energy production; (3) build a fitter mitochondrial network; (4) upregulate sirtuins and AMPK, both of which turn on and off many genes involved in healthy aging, and (5) improve how cells respond to hormones and our body clock, so that groups of cells work better together.

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* Believe it or not, I don't get any money from Neurohacker for saying any of this, even though I am on their advisory board. I am always curious to learn more, and to share knowledge on the limits and possibilities for cognitive enhancement.