Our team includes scientists from a range of backgrounds, and we think this helps us make better products than if we had a more homogeneous group of scientists. One reason for this is that people who study one thing tend to fixate on it and dismiss other options that may be advantageous. We see and hear this more or less daily when watching and listening to people opine about nutrition and supplements, and even geroscientists are prone to this: If they study α-ketoglutarate, nicotinamide riboside, rapamycin, fisetin, or some other candidate geroprotector, they tend to have bought into the benefits of their pet product and invested a lot of time studying it at the expense of learning about other candidates that may in some ways be superior options.

Next, when trying to target the biology of aging, it makes sense to zero in on the hallmarks of aging if fundamentally it is these processes driving aging. So, we do that. However, we must also recognise the limitations of these hallmarks. Consider, for example, that the process of identifying the hallmarks wasn’t some sort of unbiased, systematic analysis, but was rather a consensus from a few scientists, which was then updated in the light of more recent evidence. To make an analogy, think of the hallmarks as being a bit like a map made by early explorers based on wayfaring and setting sail across the ocean. The early map wasn’t perfect, excluding or misrepresenting various land masses. Maybe it even assumed Earth is flat. (It isn’t, by the way.) We’ve since revised this early map and can now use sophisticated systems such as GPS to precisely plot our whereabouts anywhere in the world. To build on this analogy, rather than being a map of terrestrial locations, the hallmarks are more akin to a map of nodes interacting within a network. The reason is that changing the activity of one node can affect most, or even all, other nodes in the network, and the relative importance of different nodes for different outcomes is bound to vary and interact with various factors.

The hallmarks will be revised again. And again. We’re also quietly confident that we already know of a not-yet-accepted hallmark or two at least as important as most or all of the existing hallmarks. Foremost among these is the “circadian” (meaning about 24 h) clockwork that optimises your biology and hence behavior according to the time of day. This system of clocks is truly amazing. Perhaps every cell in your body has its own molecular clock, separating the timing of incompatible processes, such as building new structures and breaking down damaged ones. The coordination of all of these molecular clocks gives rise to rhythmic changes in various tissue functions. For example, your ability to absorb, distribute, metabolise, and excrete nutrients and drugs varies according to time of day. So does your brain function, physical strength, and much more. Crucially, if you disrupt the molecular clock (genetically, for example), you can shorten an animal’s lifespan and disrupt all the other hallmarks of aging too. What hasn’t yet been shown is the flipside of this: It seems likely that if we can improve clock function during aging, we’ll also extend lifespan. There are certainly experiments that point in this direction (such as work showing that well-timed Calorie restriction extends lifespan more than mistimed Calorie restriction), but ongoing studies will shed more light on this.

We also don’t think it makes any sense to try to aggressively target all of the hallmarks in all people all the time. For example, there is substantial overlap between the proposed hallmarks of aging and hallmarks of cancer, and there is evidence that low levels of some hallmarks of aging (e.g., senescent cell accumulation) and/or trying to experimentally reduce them can drive the growth of tumours. So, in products that we make to help large swathes of the adult population, we address some hallmarks (e.g., senescent cell accumulation) with a lighter touch than others (e.g., mitochondrial dysfunction). 

We also consider what is upstream of the hallmarks of aging. The environments in which most of us now live are quite different from the ones humans evolved adaptations too. Access to electric lighting enables our 24-7 society, heating and cooling systems protect us from large changes in ambient temperature, we’re surrounded by a glut of delicious foods that we needn’t be particularly active to acquire, and psychological distress emanating from relationships, financial strain, and other sources is widespread. This mismatch between the environments we live in and the ones we evolved to thrive in contributes to many chronic diseases. 

With this in mind, we try to develop products to account for some of these upstream factors. For example, in Coastline we include ingredients that can help curb appetite and food intake (such as inulin) and counter stress responses (such as L-theanine). Further, one of the ultimate consequences of severe psychological distress can be suicide. We half joke that we couldn’t care less about the hallmarks of aging if people are trying to take their own lives. We therefore include several mood-boosting ingredients in Coastline, including one (lithium) that has repeatedly been shown to have something of an inverse relationship between intakes and risk of suicide.

We believe there are important species-specific determinants of longevity. “Model organisms” used to study aging include everything from single-celled yeast to fruit flies to mice to dogs to monkeys, and it can be informative to consider differences in the conditions and biological quirks of laboratory animals used to study aging. For example, if we take a widely-studied mammal, the mouse, many studies of mice use a genetically homogeneous mouse strain, the C57BL/6 male mouse. These mice are typically raised in conditions free of specific pathogens, without any predators, and they aren’t mixed with their female peers, remaining virgins. They also have some physiological peculiarities. For example, they aren’t melatonin proficient, lacking the nocturnal production of melatonin that helps coordinate night-time physiology in most mammals. Next, even within a species, there is variation in responses to interventions intended to extend healthspan and/or lifespan. For example, Calorie restriction remains one of, if not the intervention that most consistently extends lifespan across different animals. However, not all mice respond to Calorie restriction equally. If we then consider extrapolating findings from studies of mice to humans, we’re met with additional issues. If an intervention does on average extend lifespan in mice, it might not in free-living people. Unlike mice housed in cages, living in the big wide world exposes us to all sorts of pathogens. Some interventions that extend lifespan in other animals in controlled laboratory conditions with low pathogen burdens also suppress various immune functions, such as Calorie restriction and rapamycin. Whether these interventions would be similarly effective in the dirtier outside world is unclear, however. Similarly, while interventions such Calorie restriction are unambiguously beneficial for some organ systems in mice, Calorie restriction is not conducive to having a large, robust musculoskeletal system. This might not be a big problem in relatively lightweight, quadrupedal animals like mice — they don’t exactly have far to fall. For us more massive bipeds, however, a strong musculoskeletal system is key to independence, quality of life, and ultimately lifespan, as proven by the alarming reduction in lifespan that accompanies bone fractures late in life. In turn, the fractures lead to bedrest, accelerating loss of muscle and bone mass, exacerbating frailty.

The supplement industry is notoriously trendy, and many instances of hype have been proven to be baseless. Occasionally, bad science contributes to this. (If you’re interested, the case of HMB free acid and ATP supplements is an entertaining story. A series of studies that reported steroid-like gains were later flagged as being riddled with egregious discrepancies.) Sometimes there are bad actors at play, and there have been many instances of academic misconduct, with people fudging data and engaging in other unethical practices to further their own causes at the expense of their integrity. In other cases, there’s no compelling evidence of foul play. Nevertheless, supplements can become bizarrely popular among prominent influencers, including scientists, despite there being a paucity of convincing clinical research on these nutraceuticals. A salient example is people supplementing isolated apigenin to help them sleep, extrapolating from some mechanistic evidence and weak human trials on chamomile extracts (which contain apigenin) for sleep when at the time of writing there is no good peer reviewed clinical research on taking apigenin alone for sleep. We might discover that apigenin is indeed helpful for some sleep phenotypes, but let’s not jump the scientific gun.With respect to geroscience specifically, now and then scientists tell superficially convincing stories about putative geroprotectors and their underlying mechanisms, only for subsequent research to unveil stark flaws in their experiments. Then the bubble bursts. The story around sirtuin activators such as resveratrol comes to mind. Sirtris Pharmaceuticals was a biotechnology company intent on making sirtuin activators following hype around early work on sirtuin activators. Sirtris was sold to GlaxoSmithKline in 2008 for over $700 million. Just 5 years later, GlaxoSmithKline shut down the business following all sorts of issues, including that the activators weren’t effective. Oops.

We’re allergic to woo and believe that rigorous science is the best means we have of understanding the world. We also try to live by the old adage of making things as simple as possible but not simpler, so you won’t find us littering our messages with superfluous science jargon that sounds smart but often betrays insecurity and a lack of expertise. You also won’t find us hiding anything from you unnecessarily. Historically, many supplements have listed “proprietary blends” on their ingredient labels, listing the total mass of the blend of several non-nutrient ingredients but not specifying the doses of individual ingredients. The Dietary Supplement Health Education Act of 1994 permitted the listing of proprietary blends on supplement labels so that companies can protect their unique formulas. Honestly — and here we risk seeming cynical — the main reason manufacturers do this is as a marketing gimmick. Proprietary blends let manufacturers dodge disclosing that individual ingredient doses are well below physiologically meaningful levels. That’s not to say that proprietary blends never have any effects, but much of the time the first ingredient in the blend is a cheap nutraceutical with some noticeable physiological effects, such as caffeine, and the subsequent ingredients are present in miniscule quantities. (Note that when you read a nutrition label, the ingredients are listed in order of their proportions, with the first ingredient making up the largest proportion of the mass and the last ingredient making up the smallest proportion.) Of the different product categories that are currently popular, “greens” products are among the worst offenders.Needless to say, there are no proprietary blends in our products. We’re proud that we dose our ingredients properly. After all, we want our products to actually be effective.

We only choose active ingredients in our products that have been carefully tested and proven to be safe and effective in clinical trials. When we consider ingredients for a given product, we cast a very wide net, but we set the bar for inclusion very high. We do, however, have different levels of evidence for different types of claims that we make. For example, in analyzing the effects of ingredients on different bodily systems, we only look at clinical trials. In considering potential effects of ingredients on lifespan, however, we necessarily focus on experiments on non-human animals, for due to logistical constraints there have not been any clinical trials looking at the effects of nutraceuticals on human lifespan per se — such studies would take decades and cost enough to make Bill Gates wince. This said, if we’re considering ingredients tested in lifespan experiments in non-human animals, we only consider experiments testing nutraceuticals that have also been rigorously tested and established to be beneficial in clinical trials — we don’t include anything never experimentally shown to improve human health and function.To provide an example of a nutraceutical that doesn’t make our cut, calcium α-ketoglutarate is an intriguing case in point. This product is currently popular due to both promising preliminary preclinical lifespan experiments (the gold standard testing program did not find lifespan extension though) and an uncontrolled retrospective analysis of people taking a multi-ingredient product containing calcium α-ketoglutarate that reported reversal of a little-studied DNA methylation-based proxy of biological age clock. This research is very intriguing, but there haven’t yet been any good randomized controlled aging-related clinical trials on any forms of α-ketoglutarate (there’s one in the pipeline). Existing controlled clinical trials of α-ketoglutarate have generally had very brief interventions, have provided very high doses (sometimes delivered intravenously), have used salts other than calcium, and have been completed in clinical populations. The different salts just haven’t been pitted head to head in a rigorous clinical trial (let alone regular versus slow-release), so while calcium might turn out to be the ideal salt to pair the α-ketoglutarate with for most of us, there’s also a possibility that one of the other salts (e.g., ornithine or arginine) is superior. There’s definitely smoke there, and there might be fire. But there might not. To date the research on humans is all over the place, so it’s hard to tell.In addition, we consider studies of associations between supplement use and population health outcomes, including all-cause mortality, the most common causes of mortality, and the most burdensome chronic health conditions in terms of disability-adjusted life years and years of healthy life lost due to disability. If after trying to statistically adjust for confounding variables there is a relationship between the intake of something and such outcomes, there might be a real signal there. This is part of the reason that we find nutraceuticals such as glucosamine and lithium so interesting — the epidemiology of their use highlights potentially remarkable relationships between their intakes and morbidity, and some randomized controlled trials have yielded positive results at doses that are feasible in the context of daily life. 

Some ingredients come in many forms. An example that might be familiar is magnesium, which can be bound to a wide variety of different carriers. There’s a lot of discussion on the internet and social media about the relative merits of different forms of such ingredients, and you might have found trying to parse the different forms of nutraceuticals confusing — “should I go for magnesium oxide, citrate, malate, glycinate, threonate… or does it not matter?”.  We know your pain, and we also sometimes struggle to weigh the pros and cons of different forms of ingredients. We’ve been through this kind of analysis cycle with magnesium, coenzyme Q10 (ubiquinol or ubiquinone, oil suspension, crystalline dispersion, etc), lithium (aspartate, orotate, or another salt), and more. The reality as we see it is that sometimes forms matter a lot (as in the case of coenzyme Q10), but in other instances the product specifics matter little (sorry, but creatine monohydrate is creatine monohydrate). Still, a thorough analysis is required for each nutraceutical, and this kind of analysis often reveals that common claims about fashionable forms of supplements simply aren’t backed by the data. 

When formulating our products, we consider all sorts of interactions — interactions between ingredients, between ingredients and health behaviors, between ingredients and environmental exposures, between ingredients and medications, and more. When feasible, we look to combine ingredients that have been studied together, with known complementary effects. We know, for example that lutein, zeaxanthin, and astaxanthin pair well together (almost all of the clinical research on zeaxanthin has paired it with lutein). And it appears that inulin supplementation can improve the uptake of several minerals, including magnesium. We also try to avoid combining ingredients with known antagonistic effects at doses relevant to our products.

One of the great ironies of some of the supposedly anti-aging nutraceuticals and pharmaceuticals on the market is that they probably impair how the body adapts to healthy lifestyle behaviors. A compelling example of this is the drug metformin, a diabetes medication that some use off-label for its hypothesised anti-aging effects. Metformin is truly a great drug. It’s effective at improving blood sugar control and can thereby help in a range of disorders — diabetes, polycystic ovary syndrome, and potentially many others. It’s also very safe. However, for active people with good metabolic health, metformin might actually be counterproductive. While more research on this subject is needed, we now know that metformin can blunt how well the body responds to exercise training, including both endurance training and resistance training. The nutraceutical berberine, another agent people are taking in the hope of living longer, is uncannily similar to metformin in its effects, so perhaps it too might diminish the positive effects of exercise training. Then there’s rapamycin, a popular drug among longevity enthusiasts that inhibits mTOR. High-dose rapamycin therefore blunts the increase in muscle protein synthesis after resistance training, which is expected to reduce the ability to such training to increase muscle mass and strength. Other ingredients that might stymie your workout efforts include high doses of the antioxidant vitamins C and E, which too have made their way into some nutraceuticals intended to extend longevity.At Coastline, we want to make products that potentiate the effects of your efforts to be healthy, so when appropriate we include nutraceuticals that amplify the positive effects of a healthy lifestyle. For example, creatine stands out for its ability to increase muscle hypertrophy and strength adaptations to exercise training.

Many body clock-driven changes have important implications for how to optimise the timing of when you eat, take medications, and use other interventions to try to extend your healthspan. To give a few examples, the biological clockwork has key roles in sleep-wake regulation, and some nutraceuticals have known effects on the circadian clock, including caffeine and lithium. The biological clock also contributes to time-of-day fluctuations in symptoms of some disease states. In the case of osteoarthritis, many people have symptoms that flair in the late night and early morning, for instance. For this reason, some arthritis drugs, such as methotrexate, work best when taken in the evening. Further, an understanding of clock-regulated changes in metabolic pathways can be used to optimise responses to treatments. Many people take statins to help manage their blood lipids, and the circadian clock affects many aspects of lipid metabolism, including the activity of the rate-limiting enzyme in cholesterol biosynthesis (HMG-CoA reductase). As a result, taking fast-acting statins in the evening tends to yield the best responses to statin use. Some ingredients can affect the sleep-wake cycle independent of the circadian clock. While caffeine does seem to affect the circadian clock a little, it has more prominent effects on another determinant of sleep-wake regulation named homeostatic sleep drive. Basically, your body likes to get a certain amount of sleep (in particular of the deepest stage of sleep) and actively defends this quantity, the same way it tries to keep your blood sugar within a relatively narrow range. The main chemical correlate of homeostatic sleep drive is the accumulation of adenosine between cells in key parts of the brain. By blocking the interaction of adenosine with its receptors, caffeine temporarily reduces sleep drive, boosting alertness. Creatine, on the other hand, reduces the accumulation of adenosine. This is one of the reasons we put it in the morning step of Coastline.

Nowadays it’s common for some nutraceutical businesses to highlight the number of active ingredients in their products, as if more ingredients are better. Unfortunately for them, this is not always the case — the kitchen sink method is probably not the best way! The reality is that the more ingredients in a single product, the more interactions that are present, including interactions between ingredients and interactions between ingredients and person-level factors (nutrition, medication use, activity patterns, and so on). In our formulation process, we seek product parsimony, in the scientific sense of the term: What’s the minimum set of ingredients needed to produce the intended effects? By taking this approach, we minimise the potential for unforeseen negative interactions and help keep the costs of our products as low as is practical, which is important because we only use proven doses of ingredients.Be wary of people who boast about the number of active ingredients in their products — more is not always better!

In recent years, there’s been a rise in the number of businesses intending to make personalized health and medical products. Perhaps you’ve come across personalized nutrition companies extolling the importance of testing your gut microbiota and using continuous glucose monitoring to identify which foods are best for your unique biology, for example. The core idea that tailoring interventions to individual needs is perfectly reasonable, but the ways some of these new businesses are marketing their products is somewhat misleading, and several of these businesses are exaggerating the precision of their methods and not clarifying that there are some interventions that work well almost irrespective of who you are. For example, if you want to improve your blood glucose control, there are simple things you can do that will almost certainly reduce your blood sugar, such as reducing your carbohydrate intake, saving carbohydrate-dense items for the end of meals and snacks, and going for a walk immediately after each meal or snack. Similarly, in the world of geroprotectors, we believe there are some nutraceuticals that work well for the masses, with almost everyone benefiting from them in some way(s). These are the types of nutraceuticals that made the cut to be included in Coastline. There are definitely use cases for many other geroprotectors, but we believe that many of these other products should only be used by specific populations. GlyNAC, for example, is a very promising product, but perhaps only in certain groups of people, such as older adults and people with certain inflammatory health conditions. Similarly, we think senolytics and senomorphics are very interesting… but not a home run. We might well soon see clinical trials showing their clear advantages in several clinical populations, in particular in individuals with diseases characterised by fibrotic tissues. But there could be real negative downsides to excessively clearing senescent cells in certain contexts.

A product might be perfect on paper, containing just the right doses of the right ingredients at the right times, but if taking the product is too much of a pain — perhaps the product tastes foul or requires taking dozens of pills several times a day — then people will probably soon stop taking it. We do our best to compromise, marrying what we think is optimal with what we consider practical for most people.

We’re intent on making products that can be used by anybody with the means to afford them. For this reason, we make vegan products whenever feasible, and we avoid using unnecessary allergens.

So that we can all sleep well at night, our products are third-party tested to check their purity. In the supplement industry, this matters. There have been several horrific cases of hazardous supplements reaching the market, including a mortally dangerous fat loss supplement. While standards have improved over time, supplement contamination remains a problem. To give a recent example, two Canadian scientists bought a range of melatonin products from supplement stores. They then tested the products to see how the product melatonin contents compared to their label claims. The results were alarming: not only did the amounts of melatonin in capsules from the same product vary substantially, but the actual melatonin contents ranged from about 83% less than the label claim to about 478% more than the labelled amount. And 26% of products contained serotonin. Yikes!

In developing our products, we do much of our product testing in house, assessing effects on relevant biomarkers while gathering information about the totality of effects of our products. (We’re very happy being guinea pigs or C57BL/6 mice or whatever the appropriate comparator is!) In the future, however, we do plan to do rigorous placebo-controlled trials on our products in conjunction with an academic institution. Watch this space for more!

We’re not into adding anything non-essential to our products — every ingredient is meticulously reviewed, sourced, and tested. For example, when we consider flavoring agents such as natural flavorings, we find out exactly what the flavorings contain and reject anything that seems weird to us.

Everyone is wrong at times, and we sure are too! When we find out we are, we’ll admit it and apologise. Unfortunately, there just aren’t enough hours in the day for us to not get pushed back by the waterfalls of scientific advances that land each day.