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Everyone is aging right now, and by 2050, it's estimated that almost a quarter of the world's population will be over 60 years old. For this reason and many others, it's important that we can age as healthily as possible and reverse the damage that normally happens in our bodies as we age. In recent years, many substances, processes, and foods have emerged that have shown enormous benefits in reversing aging, from substances like NAD+ that help produce more energy in our bodies to hyperbaric chamber sessions that have been shown to lengthen our telomeres again, repairing the genetic aging that happens in our cells. Today, there are over 200 substances that we can consider as protective agents, meaning they improve our aging process, but not all are equally effective. That's why in this video, we're going to look at the 5 most promising substances for their anti-aging effects.
First, we have resveratrol. Resveratrol is a substance that is fortunately already very well-known for its positive effects on health. We normally find resveratrol in some fruits like grapes or in some berries, but the levels of resveratrol needed to generate a significant positive effect on our health are very high. We would need approximately ten glasses of wine per day, which is obviously not my recommendation. Therefore, instead, resveratrol supplementation is used. It has the ability to prevent the formation of zombie cells or senescent cells, which are cells that no longer function correctly, ruin our tissues, and prevent other cells from functioning properly. Instead of dying, they accumulate and start to affect our body. In turn, resveratrol helps us prevent the death of cells that do function correctly, reduce oxidative stress, and prevent the loss of cognitive capacity that we experience with age, because it prevents the aging of neurons. And the strange thing about resveratrol is that it shares many anti-aging effects with a process called caloric restriction, which basically implies that you can eat little to live longer, but that's not always a good option due to all the nutritional deficits associated with it. Therefore, we can use resveratrol as a substitute for this caloric restriction and have similar longevity effects without the long-term risk. Resveratrol may not have as intense anti-aging effects as other substances we will see later, but it is a safe substance to use long-term, and we can obtain the benefits of resveratrol simply by supplementing with 1,000 milligrams daily. If you are interested in learning more about these substances, I'll leave my specific video in the description.
Second, we have rapamycin. This compound is here because many of you mentioned it in the comments and wanted to hear about this topic. The use of rapamycin slows down our aging because, inside our cells, it prevents the activation of something called mTOR. Our cells have two basic states: if conditions are good, they enter a state of growth or reproduction, and when conditions are not so good, they enter a state of survival. When this mTOR activation process is slowed down, our cells stop wanting to grow, age, and differentiate, and instead enter a state of autophagy, survival, and resistance, basically to external stressors. This allows our cells to begin removing toxins, repairing damage, and recycling damaged cell components. Another interesting factor about rapamycin is that, although its studies are in mice and not in humans, it has shown to extend the lives of mice, even if it's started during old age. This is important because if it is eventually applied safely in humans for longevity, it is already used for other things, so you won't need to be young to get its benefits. In fact, rapamycin injection in old mice managed to eliminate 80% of these senescent cells, the zombie cells I mentioned earlier. And this elimination of senescent cells gives tissues the opportunity to renew themselves and keep organs younger and functioning for longer. But if it's already used in patients and even after transplants, why can't a healthy person use it for longevity? Because, while this substance has a very important anti-aging effect, it has a very significant drawback: it is immunosuppressive. It suppresses or reduces the immune system's ability to respond to external threats or infections. And while it has shown to extend life expectancy in animals, human studies are still lacking for several reasons: first, because it is a medication normally used for patients who have received an organ transplant and for whom rejection is being avoided; and second, because we haven't found a way to isolate its effects or find a dose at which it doesn't suppress the immune system. The good news is that, although we cannot use it today, there are ongoing studies to test its anti-aging effect and its long-term safety.
Even more promising than rapamycin for slowing down cellular aging are these investigations. These investigations are important because they not only have the potential to increase the years we are alive but also to decrease the onset of many of the chronic diseases that ruin our quality of life during old age. It makes no sense to live to 120 years if the quality of life you have is going to be poor. This aging, this loss of quality of life, is a consequence of many processes: the accumulation of toxic substances, genetic damage, low energy production due to lack of nutrients or lack of key substances, and many more options. That's why all substances that have the power to slow down or improve some of these processes have the potential to slow down our aging. And one of the most promising substances, according to new research, is AKG, or alpha-ketoglutarate. Today, I would say that AKG is the most promising anti-aging substance on the list for several reasons: first, because there are already very large human studies underway where participants' biological age is being evaluated to see how effective the anti-aging effect truly was; second, because it is safe to use, unlike rapamycin; and third, because its effect appears to be significantly more important than resveratrol. And third, because so far, the results of human studies have shown that its use as a supplement for seven months resulted in a reduction in biological age equivalent to 8 years. But what is this substance, AKG? It's not new; it was already used years ago by professional athletes to increase their performance. This performance increase happens because AKG is normally part of the Krebs cycle, which is a central process in our cells for controlling metabolism and energy production. And in turn, this substance is necessary for the catabolism of proteins and carbohydrates, basically to extract energy from the food we consume, from macronutrients. And it provides something called metabolic flexibility because it allows you to use the energy from proteins if you ate too much, or use the energy from carbohydrates if you ate too much. And it does much more than simply increase your energy production: it reduces oxidation, transports nitrogen, forms new amino acids, and helps you form T-lymphocytes, which are part of your immune system that manage to reduce inflammation in your body. In fact, it is necessary for almost a thousand different reactions that occur in your cells. And if you are interested in longevity or good quality of life, and you saw my video about NAD+, AKG is very similar. It is a substance that reduces with age; we lose it. We have lost the ability to produce it. When it decreases, it accelerates the aging of our cells. And it is also a substance that we normally need to produce energy in our bodies. But what are its differences with NAD+ and other anti-aging molecules like those we've already seen? AKG is not capable of extending our life expectancy as much. In fact, studies in adult mice showed only a 10% increase in life expectancy, so we don't know if using AKG for years will have a greater effect than this reduction of 8 years we are currently seeing in biological age. But, and here's the important point, the use of these substances managed to reduce morbidity by half, by 50%. This basically means that it shortens the period during which we will be sick while we are alive. The years we will live with illness will be fewer. If this is transferable to humans, perhaps we won't live many more years by using AKG, but we will spend most of our adult lives without chronic diseases and with good quality of life, which, in my opinion, is even more important.
Fourth, we have NAD+ and its precursors. Nicotinamide adenine dinucleotide is a substance that exists in all your cells. You need it for energy production, and in fact, the more NAD+ we have, the more energy we can produce, and the better our cells can function. Originally, our body can recycle the NAD+ it already has, produce NAD+ from an amino acid called tryptophan, or we can convert some forms of vitamin B3 and precursors like NMN or nicotinamide riboside to NAD+ within our bodies. But the ability to produce it decreases with age, making us increasingly susceptible to diseases and accelerating the rate at which our cells age. Because the less energy a cell has, the harder it is for it to repair the damage that leads to aging. And what's interesting about NAD+ is that it has many mechanisms, some of which can make us live longer. On one hand, it increases the expression of genes and proteins called sirtuins. These proteins and genes became famous when singer Abel lost weight using a diet that theoretically increases sirtuin activity, hence the unoriginal name "sirtfood." And on the other hand, NAD+ can improve our production of stem cells, the death of cells that still function. In fact, supplementation with precursors like nicotinamide riboside has shown to rejuvenate stem cells from different tissues and decrease the damage to our DNA with age and oxidative stress. The good news is that there are currently several human studies in progress that will soon give us much more information about the long-term effects of these substances. And if you have doubts, you have much more information in my specific video about NAD+ from last year. But as with much information about longevity, one year can imply a lot of new information. To give you a parameter, think that in 2015, intermittent fasting was seen as a very bad idea by most people.
And fifth, we have spermidine. Spermidine is a polyamine, a substance that has the ability to activate autophagy processes in our cells, very similar to what happens with intermittent fasting in our bodies, but in supplement form. There are already studies in both animals and humans, but in humans, we still have low-quality evidence, such as questionnaires that have shown that people who normally consume dietary sources of spermidine have good gut flora and produce more spermidine, have lower blood pressure, fewer cardiovascular problems, and lower mortality than people who have low consumption of foods that increase spermidine. It is believed that spermidine can improve our cellular health and be the key mechanism through which the anti-aging effect occurs, which improves our overall health metabolically, but clearly in specific effects like increasing the generation of new neurons or improving cardiovascular function. Our body can produce it in small quantities; this happens with many anti-aging substances, but it's usually not enough to compensate for the damage we generate in our cells day by day. But as with other polyamines, the bacteria in our gut can synthesize it. Therefore, the better our gut flora, the easier it will be for us to slow down the aging processes. If you're not interested in living longer, at least improve your gut flora to live without diseases for the years you are alive. And besides production in our body and production in gut flora, there are foods that are usually fermentable foods that contain spermidine, like natto or wheat germ. In my opinion, even with spermidine supplements available, it is still more convenient to dedicate your energy to having a very good gut flora, which brings many more benefits than just producing spermidine. But for whom is it worth consuming spermidine supplements? For people who cannot do intermittent fasting and want to obtain the same benefits. In the end, substances that help us rejuvenate usually have similar mechanisms: they either increase our stem cells (there's a specific video about substances that can do that in the description), or they increase energy production in the mitochondria, which are basically our energy factories, and with more energy, I can repair my body better, or they decrease cellular senescence by eliminating cells that are still alive but do nothing, these zombie cells that cause damage or prevent your tissues from functioning correctly, or finally, they reduce the damage in our cells, allowing them to be repaired, as happens with autophagy and other mechanisms when we reduce oxidative stress, and we can basically recycle old parts of our cells to use their raw material and transform it into something new.
What do we do with all this knowledge? How do we use it to live better? If we want to maximize our life expectancy, we can combine multiple strategies that have already been proven safe for humans and that do not cancel each other out. My recommendation for a longer life with less disease is to apply intermittent fasting, if I can say so. I'll leave a guide on how to do it in the description if you don't know how. Reduce the glycemic index of the foods you eat, which helps you maintain stable energy, so your blood sugar doesn't fluctuate, so your mood doesn't fluctuate throughout the day, because maintaining that stable blood sugar is key to living longer and better. Avoid nutritional deficits and reduce inflammation in your body. And if you combine all these steps with supplements like NAD+, resveratrol, or spermidine, you will be able to improve your quality of life in a non-trivial way.