Posted on Jan 11, 2022, 4 p.m.
Regenerative, anti-aging, and longevity researchers have been working to find molecules that can help to improve and/or extend both human health and lifespan. This article gathers information on some of the most promising molecules to extend human healthspan and possibly lifespan. There are also a few honorable mentions at the end of the article.
This list is heavily influenced by the Interventions Testing Program (ITP). This program selects a variety of different molecules each year to see which ones will extend mice’s lifespan. They use mice that are genetically heterogeneous, all this means is that the mice are genetically diverse and therefore minimize the possibility that characteristics of a single type of mice would affect the results. They also run these experiments at three separate labs, this is to figure out if the results are true and reproducible.
The first molecule is called glycine. When the Interventions Testing Program trialed glycine it led to a four to six percent increase in lifespan for both males and females. Now bear with me because we need to unpack this. Glycine along with another molecule called NAC (N-acetylcysteine) are building blocks for a powerful antioxidant called glutathione. In humans, the glutathione antioxidant system is maintained until around 45 years of age and then it declines rapidly. But in a 2021 human trial glycine and NAC supplementation for 24 weeks corrected the glutathione deficiency. By using glycine and NAC we can restore the glutathione balance, and now we've got human data showing a positive benefit for health.
A 2021 human trial of a group of molecules called the combined metabolic activators (CMAs) that do consist of glutathione precursors, use cuts the recovery time from COVID-19 by a whopping three days when compared to placebo. In that trial to support glutathione, they did use NAC but instead of using glycine, they used another molecule called serine. Serine is just converted into glycine by the body. Overall though for the first molecule, it's actually a combination of precursors to rebuild glutathione. The combination of glycine or serine and NAC.
Next up is nicotinamide riboside. As part of the combined metabolic activators, it also included nicotinamide riboside to help rebuild a molecule called NAD. This is important because new research has come out showing that after the age of around 60 years old our metabolism appears to tank and NAD is central to our metabolism. By rebuilding our NAD stores, we're hopefully helping to support our metabolism and therefore improve our resiliency against diseases.
When the Interventions Testing Program trialed nicotinamide riboside it did not extend lifespan. But much of the excitement around nicotinamide riboside is not to do with its potential of lifespan extension, instead, it’s because we can support our metabolism with it, which can make us more resilient against metabolic attacks. For example, sunlight, alcohol, and time zone disruption, all these things attack our metabolism, and by taking the nicotinamide riboside we may be more resilient against these attacks and that's possibly why we can see an improvement in the recovery time of COVID-19 patients.
The third molecule is 17-alpha estradiol which is a non-feminizing type of estrogen. When the Interventions Testing Program trialed it, it extended male mice’s lifespan by 19%. To stress again this is a non-feminizing type of estrogen, this is important because estrogenic actions have been increasingly recognized to have potential health and anti-aging benefits. It's not just males that seem to get a benefit from this molecule, in female mice, there's a 20% reduction in body weight. We are very excited to read more human data about this molecule.
Moving on to the fourth molecule on the list we've got SGLT2i inhibitors. This is a class of medication that is routinely prescribed to type 2 diabetic patients. When the Interventions Testing Program trialed it, it extended male mice lifespan by 14%. In humans, a 2019 systematic review was published in The Lancet journal looking specifically at heart disease outcomes involving over 34 000 patients, and what we could see in this study is that SGLT2i inhibitors reduced heart attacks by 11% and reduced the progression of kidney disease by 45%.
This medication works by encouraging the kidneys to pee out sugar, instead of that sugar remaining in the bloodstream, it's eliminated out of the system. This is important because it blunts the peak blood sugar levels which may be a factor in the lifespan extension effects that we see from the Interventions Testing Program. The potential for this molecule is because as we age our kidney function declines even from our mid-20s, and we've got human data showing that for non-diabetic kidney disease patients this type of medication does delay the progression of kidney disease. So I do wonder whether this class of medication would be used to the wider population to slow down kidney disease and therefore extend healthspan.
The fifth molecule that there is excitement about is rapamycin. Rapamycin is the golden egg from the Interventions Testing Program. Over and over again when they trial this molecule it extends both female and male lifespan, and that is why I’ve chosen to study this molecule. In a clinical trial, I want to figure out if using rapamycin once a week combined with exercise gives even greater muscle performance benefits compared to just exercise alone.
There are also three other molecules that almost made the top five list. The first one is fisetin. Essentially as we age some of our cells stop dividing and they become senescent. Fisetin does hold the potential to clear away those old cells, and that's important because those old cells don't just remain dormant they also release all sorts of factors that can damage our body. The Interventions Testing Program as part of their 2018 group of molecules will be trialing fisetin, and the Mayo Clinic have turned their attention to running human fisetin trials.
The second honorable mention is alpha-ketoglutarate (AKG), this molecule generated quite the hype in 2020 where a mice trial showed a 16.6% improvement in lifespan. We are all eagerly awaiting more human data to come out on this molecule to see whether it will improve human health.
The final honorable mention is hyaluronic acid. The quantity of hyaluronic acid gradually declines as we age, and hyaluronic acid is a major component of the connective tissue of the body including our blood vessels, skin, and organs. In a 2021 human 12-week double-blind placebo-controlled study we can see that hyaluronic acid significantly improved skin elasticity. If hyaluronic acid can improve skin health (wrinkles and dry skin) maybe it can improve blood vessel health and other parts of the body. Additionally, hyaluronic acid may also be the underlying reason as to why the naked mole rat has such exceptional longevity.
There we have an evidence-based list of top promising anti-aging and longevity molecules. But it is worth mentioning that this article is only partial, there are many others being studied looking for that elusive “fountain of youth” to help improve the human condition.
As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before making any changes to your wellness routine.
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This article was adapted from a presentation by Dr. Brad Stanfield