But supplements and longevity are very hot topics. What supplements could affect the aging process? You published some data about the anti-aging properties of alpha-ketoglutarate. Could you please talk about your research on that? Absolutely, supplements, I think, are thought to be an easy way to modify the aging process. And there were lots of supplements already on the market. And you can think about multivitamins. You can think about more specific ones, such as glycine. So specific amino acids are being given and sold already. So there's a huge market of supplements already. There is a negative side of supplements from an evidence-based medicine perspective. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. For most of the supplements, there is a very little and tiny amount of data showing what benefits somebody would have of these supplements at certain stages in life. So we need much more research on these kinds of supplements. And that's what we are doing at the Center for Healthy longevity here in Singapore at the National University in Singapore. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. We shed light on which supplement has what effect. And one of the examples is indeed alpha-ketoglutarate. Alpha-ketoglutarate is a supplement, having many functions on the pillars of aging. And I think most of the supplements will have a spread of actions. So really trying to improve or reduce oxidative stress by improving mitochondrial function and protein folding to increase that and optimize it. These kinds of supplements might have the biggest effect on the biological aging process in humans. So alpha-ketoglutarate is a supplement being investigated by Professor Brian Kennedy. It has already been shown that if you give alpha-ketoglutarate to mice, they are living longer. Still, it also might be that they are living longer and healthier, which is, of course, most important. This is the first study being done giving alpha-ketoglutarate to humans. Quite recently it was shown that the biological age is being measured by epigenetic clocks. These individuals who took that supplement were about eight years younger compared to the baseline biological age. The downside of that study was that there were no controls. And as you might know, if you're in a study or taking something, you also might change other lifestyle habits. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. So that's the reason why it's so important to have randomized controlled trials. It means the randomization. You might get the active ingredient or you might be in the control. Still, you also get the same tablet with the same size, the same smell, the same taste, the same color. We can actually be in a blinded way to analyze what works, what supplement is causally related to that effect. And this is what we are doing at the moment. We do clinical trials with alpha-ketoglutarate in a randomized controlled way. We give it to middle-aged individuals to see if their biological ages are lower. But in summary, supplements are tackling lots of aging hallmarks. Very often we do not yet really know what is the mechanism of action. But we accept that. We are targeting a lot of hallmarks of aging, because it might have a greater benefit when measuring the biological age. Apart from Alpha-ketoglutarate, from your research, what are other compounds that might have actual human evidence that is active in longevity or affecting several pillars of human aging? Yeah, we are investigating glycine, or example. That's an amino acid. Other longevity compounds are spermidine. There are mice models in our lab to see if spermidine would work in anti-aging. But you also have NMN, NAD precursors being out there already for a long time, in terms of supplementation. So there is a list of at least 20 to 30 compounds, which have the attention of researchers being in longevity trials now. For everybody who is maybe listening and saying, Okay, I would like to be included in such studies. There is on the web, there is a registration of all ongoing randomized control trials in humans, where anybody can find information on what's going on. We build the evidence for supplements for longevity, but also by repurposing drugs, for example, Metformin. We also use ACE inhibitors, or beta-blockers, and lithium. And there's also a list of 20 to 30 drugs being highly regarded to have possible neuroprotective effects. They are being studied in human randomized control trials. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. And it's very important that I mention that we need randomized control trials because we have to control for other changes, such as a lifestyle, that might be associated with lowering the biological age.
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