What is the science behind some of the most interesting supplements to slow down aging?
And how are we to find out whether these substances can actually slow down aging, especially in humans?
The truth is, it’s nearly impossible to execute an ideal human longevity study. It would require thousands of people, their consistent use of a nutraceutical, drug or therapy over the span of 30 to 50 years, and the expense of tracking their health and lifespan outcomes. Such a study would take many decades and cost dozens if not hundreds of millions of dollars.
Since none of us have the luxury of waiting decades, and the funding hasn’t been available for such studies, we have to find other ways to assess whether specific substances can positively impact lifespan.
Let’s start with the selection criteria. Ideally, the substances included in a synergistic longevity formulation adhere to the following principles:
1. They have the ability to impact at least one, and ideally multiple, mechanisms of aging simultaneously
In the last decade, scientists have described various mechanisms that cause us to age. For example, 12 important ones have been defined by longevity researchers, which we describe on our causes of aging page (R).
Some of these aging mechanisms are epigenetic alterations, loss of proteostasis (protein accumulation inside and outside our cells), cellular senescence, mitochondrial dysfunction, genomic instability, deregulated nutrient sensing, altered intercellular communication, inflammaging, and so on. Learn more about these aging mechanisms here.
Various substances have been identified that can favorably act on these aging mechanisms.
For example, fisetin can help to clear away senescent cells (R). Micro-dosed lithium and alpha-ketoglutarate have positive epigenetic effects (R,R,R). Glucosamine can favorably impact mitochondrial health (R,R). And so on.
So a powerful longevity supplement contains ingredients that each act on the hallmarks of aging. But they have to do much more than that. This brings us to the second requirement.
Ideally, each ingredient influences not just one, but multiple aging mechanisms.
For example, glycine has epigenetic effects but can also act as a chaperone, protecting proteins and reducing the risk of protein accumulation (which is one of the reasons why we age: loss of proteostasis).
Glucosamine can improve mitochondrial health by inducing mitochondrial biogenesis (R) but can also induce autophagy (the breakdown of proteins that otherwise would accumulate) (R).
In this way, combining such ingredients enables synergistic effects on the aging process. And being intimately familiar with the ingredients, their research, and their biological pathways ensures that we don’t create any dysergies.
2. They have been able to extend lifespan in various animal models, hinting at conserved evolutionary pathways
Ideally, the ingredients extend lifespan not in just one animal model, but in different species, like C. elegans (little worms often used in aging research), yeast, fruit flies, fish, mice and other species.
If the compound extends lifespan in various different species, it’s more likely it will also work in humans. Nonetheless, humans are a very long-lived species, and often the life-extension effects of specific substances measured in simple organisms are lower in humans, necessitating a more powerful approach only achieved through synergistic combinations of ingredients.
Examples of such ingredients are alpha-ketoglutarate (AKG), which extends lifespan in C elegans (R), fruit flies (R,R), and mice (R), and is also shown to reduce epigenetic age in humans (R).
Glycine can extend lifespan in C. elegans (R) and fruit flies (R), but also in mice (R) and rats (R), while it is also known to have significant positive effects on human health.
3. They are associated with reduced risk of different aging-related processes and outcomes in humans and animals, indicating that they act on the underlying aging process
The root cause of aging-related diseases such as heart disease, osteoporosis, most forms of cancer and Alzheimer’s is aging itself. Most 20- and 30-year-olds don’t get a heart attack or Alzheimer’s.
Aging is by far the biggest risk factor for these diseases.
A substance that can reduce the risk of different diseases of aging simultaneously is likely to act on an underlying mechanism that unites all these diseases, such as aging itself, or at least act on an important aging hallmark that plays a role in multiple aging-related diseases (like protein accumulation or mitochondrial dysfunction).
For example, pterostilbene has been shown in studies to reduce the risk of Alzheimer’s (R,R) and diabetes (R), while also improving cardiovascular health (R,R,R) and reducing inflammaging (R,R) and arthritis (R). These are all typical diseases and symptoms of aging.
Given that pterostilbene can also extend lifespan in animals (R), it’s likely that this compound acts on aging itself, or at least on one or multiple aging hallmarks.
4. They are associated with reduced risk of mortality in humans
Ideally, studies also show an association between reduced mortality in humans that take the supplement on a regular basis.
For example, studies in the U.S. and Europe have shown that very few supplements are actually associated with a reduced risk of mortality. One of the supplements associated with reduced risk of mortality is glucosamine.
People who took glucosamine had less risk of dying (R,R). Interestingly, people who took glucosamine also had less risk of another very prevalent aging disease, namely heart disease (R).
Other studies show that lithium, found in natural drinking water or taken in very low doses, has been associated with less mortality (R,R). Interestingly, lithium intake has also been associated with less risk of aging-related diseases such as Alzheimer’s disease (R,R,R).
5. They are nature-based, found in food or human biology, but levels decline with age
Ideally, they are nature-based and have been present alongside human evolution, and not novel man-made, lab-made molecules.
Ideally, the substances are found in our bodies, and even more ideal, the levels decline with age. This might hint at their safety and the fact that their declining levels could play a role in accelerating (or contributing) to aging.
Examples of molecules that are present at higher levels in young tissues but that decline with aging are alpha-ketoglutarate and glycine.
6. They have a (very) low side-effect profile
The substances are known to cause very few side effects (if any), and no serious side effects, even at much greater dosages than those used in the formulation.
7. They have been used for decades or even centuries to treat specific symptoms or afflictions in humans without serious side effects
Ideally, the substances also have already been used for decades or even centuries without serious side-effects or issues. An example is glucosamine, which has been taken for decades to treat joint problems (however, very few people know that glucosamine could also slow down aging (R, R,R,R)).
Alpha-ketoglutarate (AKG) is another example. This substance has been taken for many decades by elite athletes and bodybuilders to improve energy levels without any significant side effects. Alpha-ketoglutarate can also extend lifespan (R,R,R).
8. They are recognized as safe by FDA, EFSA, and other organizations
If they are recognized as safe by large, institutional bodies like the FDA (Food and Drug Administration) and EFSA (European Food Safety Agency), this could be another testimony to their safety.
Historical and Ongoing Research
As thought leaders in the field of longevity, NOVOS is the first company to target the 12 hallmarks of aging simultaneously with its formulations. NOVOS Core is based on more than 500 scientific studies that examine health benefits and the impact on the hallmarks of aging across animals and humans alike.
But at NOVOS, we don’t stop there. With our genuine intention to combat aging, we continue to run scientific studies at third party labs to further validate our formulations and make new discoveries. To date, we’ve found very substantial reductions of damage to DNA in human cells exposed to irradiation, and the ability to keep senescent cells at bay. Further, in an in-vivo case study, six months of NOVOS Core reduced the biological pace of aging, as measured by the best-in-class DunedinPACE epigenetic clock, for 73% of participants, with 0% of participants experiencing accelerated aging despite lifestyle stressors. You can learn more about our study results here.
Learn what makes NOVOS Core the best longevity supplement available here.
Discover the best science-based anti-aging ingredients here.
