And how to spot unfounded anti-aging supplements
Countless companies sell “anti-aging” supplements, each one claiming that its supplements can slow down aging and increase lifespan.
How can you know if an anti-aging supplement has scientific merit? And how to find an anti-aging supplement that could actually work?
To answer these questions, we have to discuss some of the major problems of many anti-aging supplements.
1. MOST ANTI-AGING SUPPLEMENTS ARE BASED ON OUTDATED SCIENCE
It’s strange and sad that many supplement manufacturers still believe that antioxidants slow down aging. This is despite the fact that in the past 20 years many studies have shown that most antioxidants don’t slow down aging or decrease mortality (R,R,R).
In fact, we even see that some antioxidants, such as vitamin E and vitamin A, might even increase mortality (R). Other research shows that antioxidants can undo the beneficial effects of exercise (R), or increase the risk of cancer progressing and metastasizing (R).
There are many reasons why most antioxidants don’t slow down aging. One reason is that antioxidants switch of the defense and repair mechanisms in our cells, so that cells do not produce their own antioxidant proteins (like catalase, superoxide dismutase or glutathione peroxidase), which are far more powerful than exogenous antioxidants (the ones you take orally from a supplement bottle, and that your body doesn’t make itself). Another reason is that antioxidants cannot reach high enough levels in specific compartments of the cells where they could exert an antioxidant effect. Furthermore, we see that aging is not just caused by oxidative damage, but by many other processes, like epigenetic dysregulation and protein accumulation.
Of course, there are scientific studies showing that antioxidants do extend lifespan. Often, these studies are of inferior quality. And in the cases that antioxidants do extend lifespan, it’s mostly not because of the antioxidant properties of the substances tested, but because of other reasons, like their anti-inflammatory or epigenetic effects. After all, many substances have many effects in the body, nut just an antioxidant effect.
The outdated idea that antioxidants slow down aging is based on Denham Harman’s free-radical theory of aging, which came to light in the 1950’s. It sounded good at that time, but now science has discovered that aging is far more complex than just free radicals damaging cells. We see that many other mechanisms cause aging, like protein accumulation, epigenetic dysregulation, telomere attrition, mitochondrial dysfunction (not only caused by free radical damage), transcriptomic changes, inflammation, cross-links and so on.
Some notions about aging are not only outdated, but even dangerous. Many websites advocate or sell growth hormone or testosterone to slow down aging. However, if there is one common thread running through all aging research of the last decades, it is that growth hormone and male hormones accelerate aging.
Growth hormone makes your body “grow” more and thus age faster. Many canonical aging pathways impinge on growth hormone-like pathways, like the growth hormone, insulin-like growth hormone (IGF), and mTOR pathway.
Testosterone shortens lifespan of male mice (https://www.ncbi.nlm.nih.gov/pubmed/9140897). Male hormones are one reason why men live shorter than women, and why neutered animals and eunuchs live considerably longer (eunuchs live up to 14 years longer compared to their gonad-bearing counterparts).
Of course, often, taking growth hormone and testosterone will make you feel better and younger in the short term, and you may even gain some muscle mass and lose abdominal fat. But in the long term, growth hormone and testosterone accelerate aging. People and many studies tout the short-term effects, ignoring the long-term consequences.
Some studies show that older people with more growth hormone-like substances live longer, but higher levels of various hormones can often be found in people who are healthier anyway, compared to more frail, sick or malnourished people, which produce less of various hormones because of their condition. The correlation isn’t causal.
Most (well-conducted) aging research shows that growth hormone-like substances accelerate aging, as do male hormones. People who recommend these substances to slow down aging are or not very knowledgeable about aging, or just want to make some profit (R,R,R,R,R,R,R).
2. MOST ANTI-AGING SUPPLEMENTS ARE NOT SUBSTANTIATED BY SCIENTIFIC STUDIES
Many sellers of anti-aging supplements claim that their supplements slow down aging, but mostly there are no scientific studies to corroborate this. Or almost equally bad, they quote old or ill-conducted scientific studies. Most anti-aging substances have not been rigorously tested in animals demonstrating that they can extend lifespan.
Sometimes, of course, you read about substances that do extend the lifespan in laboratory animals, but often these scientific studies have not been carried out properly or are based on bad study design. For example, a substance is tested in an animal model that does not accurately reflect aging. Take coenzyme Q10. Some studies show it can extend lifespan in mice. But that turned out to be only in mice that are genetically deficient in coenzyme Q10. Often such studies appear in scientific journals with a low impact factor, which means that these journals publish scientific studies with lower quality or evidence. It can also be that one study shows that a substance extends lifespan, while several other studies indicate that the same substance did not affect lifespan (and these studies are not mentioned by the seller).
Luckily, some people take aging very seriously and conduct rigorous scientific studies in animals to verify if specific substances can extend lifespan. An example is the Interventions Testing Program (ITP), which consists of different labs that meticulously test if specific substances can extend lifespan in mice. Unfortunately, many substances of which it is often believed they can slow down aging, such as green tea extract, curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, didn’t extend lifespan (R). Nor did resveratrol or simvastatin, and fish oil and mitoQ (R). Hitherto, the ITP labs found that only rapamycin, 17 alpha-estradiol (only in males), acarbose, NDGA (nordihydroguaiaretic acid, only in males) could extend lifespan (R,R,R,R,R).
Of course, that doesn’t mean that antioxidants, vitamins, minerals, green tea extracts, curcumin or fatty acids are useless. They are still important, given many people are deficient in these substances, or take in suboptimal amounts. Deficiencies or suboptimal amounts of these substances can shorten lifespan, or can increase your risk of all kinds of aging-related diseases. But healthy people taking extra amounts of these substances probably won’t extend lifespan.
3. MOST ANTI-AGING SUPPLEMENTS DON’T HAVE BACKING FROM ESTEEMED SCIENTISTS
Most aging scientists shy away from anti-aging supplements. Mainly because they know that most supplements don’t slow down aging. In addition, many scientists do not want to be associated with a commercial product.
So if esteemed aging scientists do support a specific formulation, very likely there will be a lot of scientific evidence showing this formulation can have a beneficial impact on aging.
Of course, scientists vouching for a specific supplement need to be real and reputable aging scientists, being very active in the field, like having published many times in leading scientific journals and running their own research lab, preferably at a university or esteemed aging institute.
Also, be careful not to buy into doctors recommending anti-aging supplements: There are many doctors who still believe in outdated aging theories, such as that antioxidants or growth hormone slow down aging, and very few (dozens, globally) who are intimately familiar with the latest longevity research.
4. MOST ANTI-AGING SUPPLEMENTS TARGET MECHANISMS THAT ARE LESS RELEVANT IN AGING
Often, anti-aging supplements focus on aging mechanisms that may be less important than others. In recent years, scientists have unraveled many mechanisms that cause us to age. These are processes such as accumulation of proteins, mitochondrial dysfunction, epigenetic changes, DNA damage, telomere shortening, and so on.
However, not all of these mechanisms are equally important. The latest research seems to hint that especially dysregulation of the epigenome is a major driver of aging. The epigenome is the complex molecular machinery surrounding the DNA that decides which genes are active and which genes are not.
In fact, when the epigenome is dysregulated, many other aging mechanisms kick into gear. A dysregulated epigenome can lead to reduced DNA repair, shortened telomeres, accumulation of proteins, and so on.
We can appreciate the power of the epigenome by looking at fascinating experiments in which old differentiated cells (like fibroblasts) can be epigenetically reprogrammed into young stem cells. These reprogrammed cells have repaired their DNA damage, mitochondrial damage, telomere shortening, and protein accumulation, demonstrating the incredible flexibility of cells and the power of the epigenome (R,R,R).
Similar clues are all around us in nature. Take queen bees for example, which can live up to several years compared to worker bees, which have a lifespan of only a few weeks, despite queen bees and worker bees having the same DNA. When a worker bee larva is given royal jelly, it transforms into a queen bee that can live twenty times longer. That is because royal jelly reprograms the epigenome of the bee.
Another hint comes from cloning. It is remarkable that a young animal can be cloned from the cells of an old animal. During the cloning process, an old, aged and damaged nucleus of, for example, a skin cell can be transplanted into an oocyte without nucleus, producing a young offspring. This means when an old nucleus is introduced into an oocyte, it becomes epigenetically reprogrammed and rejuvenated, so that a young offspring can be born.
These and many other examples seem to suggest that perhaps the epigenome is the most important driver of aging. Whether this is the case or not, it is very clear that the epigenome plays a very important role in aging. That is why we added to NOVOS various ingredients that impinge on the epigenome, like glycine, lithium, calcium alpha ketoglutarate, fisetin and NMN (nicotinamide mononucleotide).
5. MOST ANTI-AGING SUPPLEMENTS DON’T CONTAIN HIGH-ENOUGH DOSES
As a famous ancient physician already said, dosing is everything. Unfortunately, many supplements contain ingredients that are far too low, meaning that they will not have a significant impact on your health. Take magnesium for example. Many supplements only contain 50 to 100 milligrams of magnesium, while an ideal intake of magnesium is estimated to be around 400 to 600 mg per day.
It is remarkable that most anti-aging supplements are capsules or tablets. Many ingredients that can slow down aging need to be taken in doses way too big to fit in a capsule or tablet.
Take glycine for example, which can improve mitochondrial functioning and the epigenome: ideal doses are two grams or more per day. Or take malate, which also improves metabolism, which you would also need to take in the range of two grams. Other examples are glucosamine sulphate, of which you can take about 1 gram per day, or alpha ketoglutarate, that is ideally dosed at around 1 gram per day.
Before you know it, a proper anti-aging supplement would contain at least 6 grams of ingredients – that is, if you want to use substances at dosages that have been scientifically shown to extend lifespan in various animals.
Of course, there are other substances that need to be taken in small amounts, like lithium or fisetin, but the combined ingredients are too great to fit into fewer than ~10 pills.
6. MOST ANTI-AGING SUPPLEMENT COMPANIES DON’T TEST THEIR INGREDIENTS.
Most anti-aging supplement sellers don’t test their supplements in animals or humans. Mostly because they don’t bother, or because they know there is not a lot of scientific evidence corroborating their claims. Another reason is that testing in animals and humans is very expensive and requires a high level of expertise.
Also, it is not easy to test if a supplement can slow down aging, given you have to follow up the animals for a long time (until they die), which is even more difficult in long-lived humans. You can measure surrogate biomarkers of aging, like inflammatory biomarkers in the blood, or mitochondrial functioning, or physiological tests (e.g. treadmill test in old mice), but these tests are less ideal. However, this is still better than nothing.
There are many anti-aging supplements on the market. Most of them are based on outdated science, are not corroborated by well-conducted scientific studies, focus on aging pathways that are less relevant, contain doses that are too low, and are not verified in animals or humans. It is time that very science-based, well-corroborated supplements come to market. NOVOS wants to be part of this new wave of anti-aging supplements that are of great quality and are based on the best and most recent scientific insights into aging.