Evidence for NOVOS. What’s the science behind NOVOS?

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, including in humans?

It’s nearly impossible to select thousands of people and follow them for 30 to 50 years to see if they live longer to test out a nutraceutical, drug or therapy. Such a study would take decades and would cost dozens if not hundreds of millions of dollars.

Also, there currently exist no good biomarkers of aging. There are promising biomarkers in development (like epigenetic clocks), but most of them are not sensitive enough to detect a difference after taking a drug or nutraceutical for a year or even a few years.

So we have to find other ways to assess whether specific substances can impact lifespan.

Ideally, such substances are selected according to the following principles:

1. They have the ability to impact aging mechanisms (“hallmarks of aging”)

In the last decade, scientists have described various mechanisms that cause us to age. For example, 9 important ones have been described in the “hallmarks of aging” article (R).

These aging mechanisms are epigenetic alterationsloss of proteostasis (protein accumulation inside and outside our cells), cellular senescencemitochondrial dysfunctiongenomic instabilityderegulated nutrient sensingaltered intercellular communication (e.g. inflammation/inflammaging), and so on. Learn more about these aging mechanisms here.

Various substances have been identified that can act on these aging mechanisms.

For example, fisetin can clear away senescent cells (R). Lithium and alpha-ketoglutarate have epigenetic effects (R,R,R). Glucosamine can impact mitochondrial health (R,R). And so on.

So a good longevity supplement contains ingredients that act on hallmarks of aging. But they have to do more than that. This brings us to the second requirement.

2. They impact multiple aging mechanisms at the same time

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, reducing the risk of protein accumulation (which is one of the reasons why we age).

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.

3. 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 (a little worm often used in aging research), yeast, fruit flies, or mice.

If the compound extends lifespan in various different species, it’s more likely it will also work in humans. Nonetheless, humans are very long-lived species, and often the life-extension effects of specific substances measured in simple organisms are much lower in humans.

Examples of such ingredients are alpha-ketoglutarate (AKG), which extends lifespan in C elegans (R), fruit flies (R,R) and mice (R).

Glycine can extend lifespan in C elegans (R) and fruit flies (R), but also in mice (R) and rats (R).

4. They are associated with reduced risk of different aging-related diseases, hinting that they act on the underlying aging-process

The root cause of aging-related diseases such as heart disease, osteoporosis 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 of 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 can 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 aging diseases and symptoms.
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.

5. 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 US and Europe have shown that only a very few supplements are associated with a reduced risk of mortality. One of these supplements 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 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).

6. 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), which could be another testimony to their safety.

7. They are nature-based

Ideally, they are nature-based and have been present alongside human evolution, and not novel man-made, lab-made molecules.

8. They are found in the human body, but levels decrease with age

Ideally, the substances are found in our body, and even more ideal, it involves substances of which the levels decline with age. This might hint at their safety, and to 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 or glycine.

9. They have a (very) low side effect profile

The substances are known to cause very little side effects (if any), and no serious side effects, even at greater dosages.

10. They have been used for many decades to treat specific symptoms or diseases 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, that has been taken for decades to treat joint problems (however, very few people know that glucosamine could also slow down aging (RR,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).

In summary, we highlighted some ways that NOVOS uses to identify and select the most interesting and promising substances to slow down aging.

Below you can find a non-exhaustive list of studies regarding such longevity substances.