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Living longer has been a human obsession for centuries, but while medical science has helped extend average life span, not all those extra years can be healthy. It turns out that aging is a major risk factor for disease. Follow along as host Kerri Jansen and reporter Laura Howes ask if instead of extending life span, we could extend health span, and how modern science could make that a reality.
Subscribe to Stereo Chemistry now on Apple Podcasts, Spotify, or wherever you get your podcasts.
Help us shape the future of Stereo Chemistry by taking the survey at bit.ly/StereoChemSurvey.
The following is an edited transcript of the episode. We have edited the interviews within for length and clarity.
Bob Nelsen: I’m taking a lot of metformin and NMN and Elysium and, you know, that’s pretty much it. I mean, I take Lipitor, and I do like 5 days a week of 16 h fasts. And I’m looking for the right kind of supplement.
Kerri Jansen: Bob Nelsen is 57 years old. He lives in San Francisco. And for the last few years, he has followed a rigorous routine of drugs, supplements, and lifestyle habits like fasting designed to alter his body chemistry.
Bob isn’t sick. But he has a specific goal in mind with these measures. He’s conducting an N = 1 experiment on himself in an attempt to slow down the process of aging.
Bob Nelsen: You know, I generally kind of have a fear of death, which is part of, you know, what motivates me to be interested in longevity. So it is a selfish thing.
And I have no idea whether it works. You know, I don’t feel my age.
Kerri: Bob is a biotech investor, so his job is to spot trends in health and technology to build companies he thinks will make breakthrough, transformative science. It’s through that work that Bob was exposed to an array of relatively recent biochemical discoveries in aging research, which are for the first time starting to expose the molecular mechanisms that underpin the aging process and open the door for treatments that could potentially prevent or reverse those changes. At the same time, a handful of existing drugs have serendipitously been observed to slow aging, leading to a new wave of interest in longevity. And Bob is far from the only person to become captivated by the idea of staving off the decline of age.
In this episode of Stereo Chemistry, we’ll hear from some of the scientists who are teasing out the biochemical secrets of aging. We’ll look at the drugs that are in development right now to tackle aging at the molecular level, and we’ll find out what we know—and don’t know—about this biological process that affects all of us. I’m your host, Kerri Jansen.
Kerri: For this episode, I’ve asked C&EN reporter Laura Howes to join us. Laura is based in Heidelberg, Germany, and covers chemical biology. Thanks for joining us, Laura.
Laura Howes: Hi, Kerri.
Kerri: Laura, it wasn’t until we started working on this episode that I realized I don’t really have a great sense of what it means to age. I mean, we think of getting older, the passage of time. But, scientifically, what is aging?
Laura: That is a great question, Kerri. And one I asked a lot of different people in recent months. And you know what, there are lots of different ways of thinking about aging. But we all know what it can look like: over time you have less energy and less strength or vigor. At the same time, smell, taste, eyesight, hair, and muscle tone—all of it starts to just change a little bit as your biochemistry changes.
Kerri: And those biochemical processes are at the root of what we’re talking about today. Can you give us an overview? What does aging mean at the molecular level?
Laura: Well, there are a lot of things going on. For one, there’s low-grade, chronic inflammation. Inflammation is switched on as part of a healthy immune system to coordinate fighting infections and repairing damage, but as we age, chronic inflammation can start hammering our cells and tissues, causing damage. And then there’s also a whole host of processes happening inside cells. There are chemical changes to DNA that alter how the cells keep working: proteins misfold and clump together, which stops them working properly, and the mitochondria in the cell don’t work properly, which changes metabolism. And different types of cells can change: stem cells stop being able to create new healthy cells, and you also start accumulating a particular type of cell that can cause damage. Those are called senescent cells. Senescent just means “old.” These senescent cells are going to come up a lot in this episode—they’re a key target for many of the treatments being developed.
Kerri: So if we’re talking about disruption and damage inside the body, is aging a disease?
Laura: No, everyone I spoke to for this podcast was pretty clear about that. For one thing, there’s enough ageism in the world without othering older people even more. But also, researchers don’t think everything about aging is bad. Instead, as scientists understand more about the different ways our biology changes as we age, they can also see how those fundamental aging processes can contribute to disease. I talked with James Kirkland, a gerontologist at the Mayo Clinic who also researches how aging can affect diseases. He told me aging is actually the number one risk factor in disease.
James Kirkland: For example, 80% of the risk of getting Alzheimer’s disease can be predicted from knowing a person’s chronological age alone. The relative risk of having a heart attack has increased two- to fourfold by having high blood pressure, high blood sugar, high cholesterol, positive family history, but it’s increased by over 100-fold if you’re 85 as opposed to 35. So if you put aging as a risk factor for any of the major chronic diseases, and if you draw histograms, bar graphs, and you put aging as a risk factor, you don’t even see the other risk factors.
Kerri: And we’ve seen that with COVID-19 as well. Older people are more likely to get severely sick when infected because their immune system is weaker than younger people.
Laura: Right. And their immune system is weaker in part because of that buildup in senescent immune cells and amped-up inflammation.
So this gets at a key aspect of antiaging research. The biochemical processes of aging make other diseases worse. So for many researchers, slowing the progression of aging isn’t about being able to live forever. It’s about making the life we have healthier. Increasing health span, not life span. Here’s Bob Nelsen again.
Bob Nelsen: I don’t really want to just live a long time without having, you know, truly an increase in health span. So I like this idea of, you know, being like that little thin little old lady 100-year-old that you see whose mind is, you know, sharp and you know everything kind of working just fine. And that seems to be an OK state to me.
Kerri: So at the beginning of this episode we heard Bob list a whole bunch of drugs he’s taking in an effort to extend his health span. Where is the science at on those?
Laura: Right. He mentioned Lipitor, which reduces cholesterol, and NMN—that’s nicotinamide mononucleotide, a supplement that in mice has been shown to boost metabolism—and Elysium, a dietary supplement that’s advertised to improve cellular aging. He’s also taking metformin. That’s a drug that is commonly used as a diabetes treatment but has recently been getting a lot of attention in the aging-research community. We’ll talk more about that in a moment. And then there are two other main types of drugs aging researchers are interested in. One type is senolytics, which help rid the body of senescent cells that accumulate as we age. And another class of drugs is called rapalogues. Rapalogues target a specific series of biochemical reactions that are involved in aging. Rapamycin was the first of these to be discovered. Rapalogues are similar compounds that have since been designed to do the same thing.
But to be clear, we’re not advocating you take any of these—we don’t yet know what the negative impacts could be for taking them for aging—and any changes you do want to make to your lifestyle should only be in consultation with a doctor.
Kerri: That’s important, so let’s hear it one more time.
Laura: We’re not advocating you take any of these.
Kerri: Got it? OK. Let’s move on.
Laura: As researchers have come to understand more about how aging works, they’ve now got to the stage where some are setting up trials to see whether different drugs can improve how we age. So we’re going to talk to some of the researchers involved in these trials as well as academic researchers who think there’s a lot more to be uncovered about how aging works in our body.
Nir Barzilai: If there are aliens, and they will come here, they’ll be shocked to see older people. They would say, “You didn’t deal with that?”
Laura: That’s Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine.
Nir Barzilai: If they came farther than Mars, right, they solved aging.
Laura: I don’t think Nir does actually expect us to be visited by aliens, but it’s interesting to consider that we don’t necessarily have to accept aging in its current form. Nir also noted that the health issues traditionally linked with aging are not limited to folks with an advanced chronological age.
Nir Barzilai: It’s not about the older adults only. People who are treated for cancers with chemotherapy and radiation—that, by the way, are inducing aging quite effectively—they’re getting older. In particular young people, they’re getting older. Young people after therapy get second cancers, too, but they get a heart disease and, you know, hypertension. They get other diseases. People with HIV have age-related disease 10 years earlier than other people.
Laura: Nir has several interests and ideas for how to treat aging-related health issues, and one of the drugs he’s very interested in is metformin.
Kerri: Right. You said that drug has been really popular lately in aging research. So why is that?
Laura: Well, that drug has actually been around for more than 60 years as a treatment for type 2 diabetes. It’s a small molecule, and in people with diabetes, it decreases glucose production in the liver. But in 2014, a group of researchers at Cardiff University in Wales found that people with type 2 diabetes who were taking metformin live longer on average than people without diabetes who didn’t take the drug. That caught the interest of a lot of researchers, including Nir. He is especially interested in metformin because of its long track record of use—millions of people have used it safely for many years.
Nir Barzilai: There are billions, years of use. And we know everything we need to know about metformin: it has a spectacular safety record; its major side effects is that you live longer.
Laura: The safety record of metformin is why Nir says he’s opted to trial that drug over senolytics and rapamycin, as well as the fact that it’s very cheap in comparison. But he expects that all the drugs we discuss, and other treatments, might end up being used in combinations. One thing you realize as you learn more about this field is that it’s not enough to simply say that one drug affects one protein, which then affects a single chain of reactions. Instead, it’s more like an interconnected web. Each drug might affect one section of the web more than others, but they can all have effects. That’s another big plus in Nir’s book.
Nir Barzilai: I believe that we have to look at all the hallmarks to develop drugs for all the hallmarks of aging. The effect of drug like metformin on health span, we predict it’s going to give you 2 years, an additional 2 years of health.
Kerri: So that’s a big claim. But what does the data say? Is metformin living up to the hype on aging?
Laura: Well some doctors will already prescribe it off label even if you’re not diabetic. That’s how Bob got hold of his. But there hasn’t yet been a clinical trial to show that it slows aging. Nir is trying to start up a trial to see if metformin can live up to the hype. The trial is called TAME—T-A-M-E—Targeting Aging with Metformin.
It’s currently paused because of the pandemic. But I find the trial design itself really interesting. Instead of looking at whether the drug affects a specific disease, they’re just going to look and see if metformin makes a difference to a whole range of age-related diseases. Nir plans to give metformin to over 3,000 people and monitor them over 6 years to see if the onset of various diseases, like stroke or heart failure, can be delayed.
Nir Barzilai: Our approach is, look, we’re saying that we’re going to delay aging, and we’re going to delay diseases. We are totally agnostic to which disease we have to target. OK, we don’t care what disease you have. And we don’t care what disease you’re going to have, whatever it is.
Kerri: OK, so scientists are testing whether metformin improves health span a little, in a general sense. What about those other treatments you mentioned?
Laura: Right, so senolytics and rapalogues. Let’s start with senolytics. Those caught the attention of aging researchers around 2013, and they kill senescent cells.
Kerri: Let’s talk a little more about senescent cells. You said that they’re a type of cell that accumulates as we age. How does that end up causing problems in our bodies?
Laura: OK. If you think back to biology class, you might have seen videos of cells dividing. Well, senescent cells are cells that stop dividing but also don’t die. And mostly these cells are useful. They help stop cancers; they are involved in wound healing and fetal development. But at some point, as we age, these senescent cells collect up and start causing problems, secreting chemicals that cause inflammation—things like cytokines, chemokines, and proteases. Here’s gerontologist James Kirkland again:
James Kirkland: What we’re trying to do is get rid of senescence cells that have outstayed their welcome, where they’ve started to dampen down the immune system—which normally clears them—and where they’ve gone beyond what we call a threshold effect, where their rate of formation exceeds the ability of the immune system to clear them.
Kerri: Got it. So how do senolytics work to get rid of senescent cells?
Laura: Sneakily. A bit like some cancers, senolytic cells are very resistant to dying. Instead, they live on, damaged and giving out a toxic mix of proteins and other compounds that cause neighboring cells to die. You can think of them as zombie cells.
Kerri: OK.
Laura: If these zombie senescent cells aren’t kept in check, they can slowly cause more and more damage. James and his lab wondered how these senescent cells could survive when they were kicking out cell-killing poisons. They found that senescent cells have internal defenses to protect themselves from these toxic compounds. If you knock out those defenses, the cells will die. In 2013, the researchers discovered that two existing drugs—one is a cancer treatment and the other a supplement—could kill these zombie cells by targeting these newly identified pathways. Since then, more defenses and more senolytic compounds have been discovered.
James Kirkland: Well, we’re working as fast as we can, and it has been quick—you know, we only discovered the drugs in May 2013 and published them in early 2015. And already, you know, there are multiple clinical trials going on.
Laura: But there’s no telling whether they will work—it’s worth remembering that no drug has been shown to be safe and effective for aging.
Unlike the metformin study, the trials James is running are trying to see if senolytics can reduce specific markers of aging in people who are very sick with aging-related diseases. But instead of taking a daily pill, like metformin, volunteers in the study get a short course of these two drugs or a different senolytic—a short, sharp shock that’s meant to clear out the senescent cells and then reset the amount in the body to more youthful levels.
James Kirkland: We’re interested in a hit-and-run approach, much like is used for treating certain kinds of infections. We sort of view senescent cells like a bad bug, like bacteria that we wanted to get rid of.
Laura: Keep in mind, although some pilot trials with senolytics suggest they work, there’s a long way to go before those drugs might be prescribed. That’s the same for the class of treatments called rapalogues—those are the third kind of drug that people think could help extend health span. The hope is that rapalogues could reverse some of the effects of inflammation. The term rapalogue, by the way, is a shortened form of “rapamycin analogue,” because those drugs are related to the compound rapamycin.
Kerri: Right, rapamycin is a compound produced by bacteria that has turned out to have a lot of medicinal properties. Our colleague Beth Halford did a deep dive on that compound a few years ago.
Laura: Yeah. Rapamycin has been touted as an anticancer drug because it stops cancer cells dividing. And researchers have found that it also inhibits the series of reactions started by a protein that scientists named mTOR, which stands for “mechanistic target of rapamycin.” What’s interesting about rapamycin and mTOR is that mTOR has been shown to act like a control system for coordinating how cells manage their nutrients, which is something we know gets out of whack when people get older. Then in 2009, researchers found that in mice, rapamycin could extend the life span by about 9–14%. James Kirkland again.
James Kirkland: Drugs related to rapamycin, there are many of them. Many of them are used now as immunosuppressants to prevent graft-versus-host disease after transplantation. They act on senescent cells to prevent senescent cells from producing a lot of proinflammatory factors.
Kerri: So there are senolytics that can get rid of excess senescent cells, and rapalogues that can tamp down the inflammatory compounds senescent cells give out and also prevent new senescent cells from being formed.
Laura: Yeah. And James told me metformin, the other drug we’ve discussed, can also reverse some of the damage caused by senescent cells. Both he and Nir think all these treatment options might be needed as well as some other, new approaches. Remember, the treatments we just discussed are all based on drugs that were developed to target things other than aging. They just happen to affect the markers of aging too. The next phase is for researchers to develop drugs specifically for aging-related problems, and that’s a really exciting field right now. There’s a lot of work still to be done.
Kerri: We’re going to take a quick break. When we come back, we’ll hear about the next generation of aging treatments and how researchers are working to turn serendipity into science.
Kerri: Hi everyone. It’s me again, Kerri Jansen, your Stereo Chemistry host and producer.
We’ve been making Stereo Chemistry for 3 years now, and first of all I want to say thanks to all of you who tune in every month, subscribe and rate the show, and engage with us on social media. It’s because of you that we’re able to bring you stories about cutting-edge research, chemistry culture, conversations with Nobel laureates, and more. And we’re so excited to keep sharing these stories from the world of chemistry.
And now, we want to hear from you. We are conducting a survey of podcast listeners to help us decide the future path of Stereo Chemistry. We want to know what you like, what you don’t like, and what you want to hear more of.
So if you’d like to help us shape the future of Stereo Chemistry, here’s what you do: Go to the link bit.ly/StereoChemSurvey. Fill in as many answers as you like and hit submit. You’ll be entered for a chance to win a $25 Visa eGift card.
Once again, the survey link is bit.ly/StereoChemSurvey. We’ll put that link in this episode’s show notes as well.
Thanks again for listening. And now, back to the show.
Kerri: So, Laura. We’ve just heard about three classes of potential antiaging treatments based on existing drugs. And you said that some researchers are now exploring a more targeted approach. Tell us about that.
Laura: Yeah, this is something we’ve started to see pretty recently, researchers drilling down into the specific biochemical processes of aging to develop new drugs to target them. It’s only in the last 10 years or so that we’ve begun to understand the specific molecular mechanisms that underpin aging.
Kerri: And we’ve already heard that the process of aging is really complex. So what was the breakthrough that enabled scientists to start to figure this out?
Laura: Well, actually, it has to do with diet. Remember, at the beginning of the episode, Bob said he fasts several times a week, in addition to taking all those drugs? And he’s not the only one who does. Now, the scientists I spoke with noted the jury is still out on whether that can slow aging in humans—and, again, if you’re considering making any kind of big change to your diet, talk to your doctor first. But calorie restriction, or CR, has been a key part of aging research for a long time. It means exactly what it sounds like: limiting calorie intake, either through smaller meals or reducing the frequency of meals. In animal studies, it’s generated some pretty interesting results.
Roz Anderson: And I thought, How is it possible that something so simple, could, you know, influence something so complex?
Laura: That’s Roz Anderson, who studies aging and diet at the University of Wisconsin.
Roz Anderson: And I got hooked on the biology. So for me, it was never really about, you know, living longer, or anyone else living longer, for that matter. It was just the straight-up biology.
Look at it this way. It’s amazing. It works in a yeast, in a fly, in a worm, in a mouse, in a rat, in a dog, in a monkey. It seems to be a very, very fundamental process, that caloric restriction is kind of catching ahold of.
Laura: Roz first got hooked on the basic biology of aging during her postdoc. She has found that in many animals, calorie restriction can have a dramatic effect on how well and how long the animals live for.
Roz Anderson: This is where something like CR becomes, like, super cool, because we know we’ve changed the pace of aging in the CR animals. We know they live longer, we know they have less disease, and what disease they have progresses more gradually.
Kerri: Wow. Do scientists know how exactly calorie restriction is having this effect?
Laura: We don’t entirely know, but researchers like Roz know it changes the metabolism and signaling reactions in our body, including some of the same pathways that are influenced by the drugs like metformin and rapamycin that we discussed earlier. Roz is one of the researchers trying to figure out more about how fasting helps change aging. The potential she sees is not necessarily about proving the value of a new fad diet. Rather, it’s a way to uncover the key biochemical processes involved in health and aging.
Roz Anderson: Fasting-mimicking diets, time-restricted feeding, every-other-day fasting, all of these paradigms do show terrific promise if you’re a mouse. But I think, I think we will be able to, you know, tease out what the beneficial components are.
Laura: For example, if you trace back the development of senolytics, you find that people became interested in senescent cells because mice on restricted diets were found to live longer and have fewer senescent cells. Roz is mostly interested in using the biological changes induced by calorie restriction to puzzle out the biology behind aging and how it works. Other researchers are using genetically modified animals to probe those biological changes. And, most recently, researchers are also starting to use large-scale laboratory analysis and AI to try and build up a descriptive picture of how we age and how that varies from person to person.
Kerri: And what do you mean by that?
Laura: Well, think of it this way: I’m about to turn 38 [sigh]. But we’ve been talking about how in the future I could slow down or reverse some of the biological processes associated with aging. So the dream is to measure a bunch of different markers and then be able to separate biological age from chronological age. Then, scientists might be able to advise an individual how to change or improve their health based on their specific aging profile. That individual-focused approach would be a big change from how aging research has historically been done. At Stanford University, Mike Snyder has been working on this for several years.
Mike Snyder: So traditionally, the way people followed aging was measure a bunch of old people and a bunch of young people, and they’ll say, “Well, these are the markers in old people, and these are the ones in young people.” And a good example is hemoglobin A1c.
Laura: Hemoglobin A1c is an oxygen-transport compound in blood that is chemically linked to a sugar and is used to monitor people with diabetes or prediabetes.
Mike Snyder: We know that goes up with age, and we say, “OK, these are markers of aging.” And they’re, they’re valid, it’s true. But what’s very interesting is we don’t really know how they work at the individual level. And again, that’s where we come in, because we’ve been profiling people while they’re healthy. But we can see how they’re aging over time. You know what’s going on. And what we discovered is about 600 molecules that do change in people over time. But they don’t all change the same in all people.
Laura: Of course, an individualized approach to studying aging will generate a massive amount of data. Mike actually started this study by monitoring his own health. To date, he says, he has about 2 petabytes of data relating to him, and a petabyte is a million gigabytes. He also has another 2 petabytes that cover the participants in his research study. And that’s where computational algorithms come in, to process that data. Scientists hope to use AI to identify how individuals are aging and what changes they can make to their lifestyles to slow that down. Bob Nelsen is convinced that’s going to be a key growth area in the next few years, as machine learning and an understanding of key pathways to measure both improve. That could put this research—and the treatments it may yield—on the fast track.
Bob Nelsen: And I do think it will transform health care as we know it in the next 10 or 20 years for sure. You can think of aging-related diseases as really the most expensive, the most impactful, and the deadliest thing that we deal with.
I mean, I’m interested in longevity because it applies to me, right? And I am interested in it as a societal problem, and I love the idea of preventing disease. But like, you know, it has occurred to me that I would like to live a long time. And so I’m not pretending that it’s some egalitarian act and the only thing that I’m interested in, is that, you know, that I hope it prevents disease in everyone else. Like, I’m pretty interested in preventing disease in me too.
Laura: And as more investors like Bob get behind aging-related projects, scientists are expecting an explosion of new discoveries. Nir is one of them.
Nir Barzilai: So we’re catching a wave. I would describe the wave as it’s going slowly, but it’s going to be quite big when it gets to its peak. And I think that the next few years will be remarkable in what we can do and what we can show to everyone.
Kerri: So what about you, Laura? Are you itching to get your hands on these treatments?
Laura: Well, I’m not about to start taking a lot of the drugs we’ve discussed in this podcast—and, again, we’re not advising any listeners to do that either; we don’t yet know what all the downsides might be. But I am interested in following the data. And I’d be lying if I said that the promise of extending my health didn’t appeal. The idea that Bob mentioned at the beginning of the show, of being a sharp old granny who is still living independently, sounds pretty good. It’d be even better if my knees and my internal organs were all still working into my 90s.
Kerri: But do you think that’s possible in our lifetimes?
Laura: Actually, I’m more positive about that future than I was when I started talking to people about their work studying aging. And one reason is that several of the researchers told me that it’s looking increasingly likely that many different processes in aging are very tightly interlinked.
You remember how early in the episode we talked about how we can think about the biochemistry of aging as kind of like a big web? James told me that the evidence is growing that targeting one of the biochemical processes of aging might actually help with all of them. It’s what he calls the unitary theory of fundamental aging processes.
James Kirkland: It’s still a theory. But it’s looking increasingly like all of these processes are very tightly interlinked, such that if you intervene in one, you tend to affect all the rest. In fact, we haven’t found exceptions to that so far.
Laura: And so even though aging is very complex, biochemically, it’s also so interlinked it might not need a different drug for each set of reactions or pathways, just a few tuned to your immediate needs. And that might mean that the idea will change of what aging is biologically to be a more granular understanding that researchers like Roz and Mike are building. I think for now I’m just going to keep on trying to eat healthily, exercise, and socialize with friends (as much as the current pandemic allows). Everyone I spoke to could agree that those were good ideas. But perhaps aging research will help us understand how to be even healthier into our old age.
James Kirkland: I’m very tired of prescribing better wheelchairs, walkers, and incontinence devices. And all of us, I think every geriatrician, wants to get something more fundamental out there, whether it’s going to be some senolytics or some other intervention. I hope something comes along.
Kerri: This episode of Stereo Chemistry was written by Laura Howes and produced by me, Kerri Jansen. Story editing by Lisa Jarvis and Amanda Yarnell. Production assistance by Gina Vitale. The music in this episode was “Paradise Drive,” by Charlie Ryan, and “Bounce,” by Seth Parson.
Laura:Stereo Chemistry is the official podcast of Chemical & Engineering News, which is published by the American Chemical Society.
Thanks for listening.
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Aging may be inevitable, at least for now, but that doesn’t mean we have to sit back and just let it happen. Increasing lifespan and slowing the aging process has been the focus of much scientific research over the decades and as such a variety of substances have been identified that possess anti-aging properties that may help to decelerate the process.
This is a collection of a few for your review, but keep in mind this is just a short list that is in by no means exhaustive, there are many other supplements that may also offer anti-aging effects.
Curcumin/turmeric has been shown to carry anti-aging properties which have been largely attributed to its potent antioxidant potential. This compound has been demonstrated to activate certain proteins which may help to delay cellular senescence and promote longevity, as well as being associated with a reduced risk of age related mental decline in humans. Additionally it has been shown to combat cellular damage and increase the lifespan of mice, roundworms and fruit flies and postpone age related disease while alleviating the symptoms of age related disease. 
EGCG is a polyphenol compound that is found concentrated in green tea that carries some impressive health benefits that are backed by science including reducing the risk of certain cancers and other conditions such as heart disease. Epigallocatechin gallate has an array of potential health promoting properties such as promoting longevity, protecting against age related disease development, restoring mitochondrial function in cells acting on pathways involved in aging, inducing autophagy, as well as being associated with a reduced risk of all cause mortality, diabetes, stroke, and heart disease. Animal studies have shown it to protect against skin aging and wrinkles caused by exposure to UV lighting. 
Coenzyme Q10 is an antioxidant produced in the body that plays roles in energy production and protection against cellular damage. However, levels of this decline with age, supplementation has been shown to help improve certain aspects of health in older individuals such as reducing oxidative stress that accelerates the aging process and onset of age related disease. 
Nicotinamide riboside and nicotinamide mononucleotide are precursors to nicotinamide adenine dinucleotide which is found in every cell and involved in many critical processes including energy metabolism, DNA repair, and gene expression. However, levels of this also decline with age and it is thought to be associated with accelerated physical decline and the onset of age related disease. 
Crocin is a yellow carotenoid pigment in saffron that carries many health benefits including anticancer, anti-inflammatory, anti-anxiety, and antidiabetic effects. It has been studied for its potential to act as an anti-aging agent and ability to protect against age related mental decline. It has been shown to help improve aging in human skin by reducing inflammation and protecting against UV light induced cellular damage. Animal studies have demonstrated prevention against age related nerve damage by inhibiting production of advanced glycation end products and reactive oxygen species that contribute to the aging process. 
Resveratrol is a polyphenol that may help to promote longevity by activating sirtuins genes, and it has been shown to increase the lifespan of nematodes, yeasts, and fruit flies. It may help to lower cholesterol, protect brain function, increase insulin sensitivity, ease joint pain, suppress cancer cells, and lengthen lifespan in certain animals. 
Quercetin is a natural antioxidant pigment found in many grains, fruits, and vegetables that plays important roles in helping the body combat free radical damage that is linked to chronic diseases. It may help to reduce inflammation, blood pressure, boost immunity, aid exercise performance, reduce allergy symptoms, and help maintain general health. 
Fisetin is an antioxidant flavonoid that is a senotherapeutic, which means that it can kill harmful senescent zombie cells. Animal studies suggest that it may help to reduce the number of these cells in tissues to help extend lifespan. It is active against allergic inflammation and has gained attention for its memory enhancing capabilities in animal studies. 
These are just a few supplements that might help to slow the aging process and promote a long and healthy life. CoQ10, crocin, festin, curcumin, and NMN are just a few of the compounds that have been shown to offer anti-aging effects in scientific research studies.
While some studies suggest taking supplements may help to slow the aging process the best way to promote longevity and overall health is to follow healthful practices which involves keeping stress in check, getting enough sleep, being physically active, and maintaining a nutritious diet.  It is also recommended to consult with your physician or certified medical professional before taking any supplement to avoid possibility of complications. 
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Content may be edited for style and length.
This article is not intended to provide medical diagnosis, advice, treatment, or endorsement
https://www.healthline.com/nutrition/quercetin
https://www.healthline.com/nutrition/resveratrol
https://www.sciencedirect.com/topics/neuroscience/fisetin
https://www.healthline.com/nutrition/anti-aging-supplements

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“We had a little dinghy with a 15-horsepower motor. As a young teenage kid, having that freedom to go fishing, sailing, windsurfing – that’s a life that I really miss,” he said.

Professor Sinclair works at the Department of Genetics at Harvard Medical School. He’s Australian and grew up on Sydney’s northern beaches.

“I’m here in Boston and the water is freezing cold. You don’t go windsurfing unless you’re insane. I did buy a house on the water to try to recreate that life for my kids, but it’s just not the same as being on a beautiful, warm, flat lake.”
In 2014, Time Magazine listed him among the “100 Most Influential People in the World”. In 2018, Time listed him in their top 50 people transforming healthcare.

The reason is his work on longevity. He was due in Newcastle in early April to attend the Newcastle Writers Festival to discuss his recently released book, Lifespan: Why We Age – and Why We Don’t Have To.
Professor Sinclair believes ageing is a disease. Not only that, he believes ageing can be put in remission and that age-related diseases can be prevented and reversed.
“I don’t want to cure ageing. That’s not what I’m trying to do. I’m trying to keep people healthier for as long as possible – to improve the body’s defences against disease,” he said.
He has called for greater international attention on the social, economic and political risks and benefits of a world in which billions of people can live much longer and much healthier lives.
He’s working on medicines that enable people to live healthier for a longer time.
And he’s more than happy to use himself as a guinea pig. The results are impressive. Blood tests show his biological age is much lower than his real age. His father – who is in his 80s – is also showing remarkable results from his anti-ageing regimen.
“Right now medicine is able to treat diseases once they occur, which is often too late,” he said.
“I call it whack-a-mole medicine. Our approach has been to find the body’s defences against the ageing process.”
He’s concerned with what makes people sick in the first place.
“Young people don’t get heart disease or Alzheimer’s. There’s a reason for that.
“If you’re not sick and you stay healthy, you tend not to die.”
The professor has spoken about his personal anti-ageing regimen, which includes taking supplements and drugs called NMN, metformin and resveratrol [which occurs naturally in small doses in things like red wine and blueberries].

His research shows that resveratrol should be taken with some fat to be properly absorbed. He mixes it with yoghurt.
“I’m definitely not the kind of person who says go and buy a supplement. I’m not selling anything. I don’t want anything to do with supplement companies,” he said.
Asked the cheapest way to seek longevity, he said: “Eat less often”.

Of course, this doesn’t mean starvation or malnutrition. But he is a proponent of intermittent fasting.

“The idea of always being satisfied is very 20th century. The 21st century is where our bodies need to be put in a state of adversity, call it hormesis,” he said.

“It basically means that if we’re never hungry, we’re never moving and never out of breath from running, our bodies don’t bother being strong. They become complacent.

“We found the genes that underlie those processes. We’ve got seven of these genes. They’re called sirtuins. They turn on the body’s defences against ageing and the diseases that come with that.”
He said people can eat less often, exercise and eat the right foods to help ward off the diseases of ageing. But more people will increasingly have the choice of taking medicines and supplements that artificially turn on the affected genes to give the health benefits, without necessarily having to do the required levels of exercise and proper eating.
Professor Sinclair appears to have a long life ahead of him. And he loves to return to Australia.

“I come back any excuse I can get,” he said, adding that he hopes to one day attend the Newcastle Writers Festival when the world returns to normal.
You know you’re getting old when: Everything that works hurts, and what doesn’t hurt doesn’t work.
You feel like the morning after and you haven’t been anywhere.
Your children are beginning to look middle-aged.
You look forward to a dull evening.

Your knees buckle and your belt won’t.

Your back goes out more than you do.

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The answer appears to be yes, at least in mice, according to a new study led by investigators at Harvard Medical School.

The research, published March 22 in Cell, identifies the key cellular mechanisms behind vascular aging and its effects on muscle health and has successfully reversed the process in animals.
Get more HM news here 
The findings pinpoint a glitch in the normal crosstalk that occurs between muscles and blood vessels and keeps both tissues healthy.
Using the synthetic precursors of two molecules naturally present in the body, the scientists also managed to reverse blood vessel demise and muscle atrophy in aging mice, boosting their exercise endurance in the process. 

The achievement, the team said, paves the way to identifying related therapies for humans.

“We’ve discovered a way to reverse vascular aging by boosting the presence of naturally occurring molecules in the body that augment the physiological response to exercise,” said study senior investigator David Sinclair, professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School.
“The approach stimulates blood vessel growth and boosts stamina and endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging,” added Sinclair, who is also a professor at the University of New South Wales School of Medical Sciences in Sydney, Australia.
The researchers caution that many promising treatments in mice don’t have the same effect in humans due to critical differences in biology. However, the results of the experiments were dramatic enough to prompt the research team to pursue experiments in humans. Clinical trials for safety are already under way, Sinclair said. 
As old as our blood vessels
Sinclair and team set out to unravel the mechanisms behind one of biology’s inevitabilities: aging. 

As we grow old, we become weak and frail. A constellation of physiological changes—some subtle, some dramatic—precipitate this inevitable decline. What exactly happens inside our cells to cause the biological shifts that lead to aging? It’s a question that has vexed Sinclair and team for years.

As we age, our tiniest blood vessels wither and die, causing reduced blood flow and compromised oxygenation of organs and tissues. Vascular aging is responsible for a constellation of disorders, such as cardiac and neurologic conditions, muscle loss, impaired wound healing and overall frailty, among others. Scientists have known that loss of blood flow to organs and tissues leads to the build-up of toxins and low oxygen levels. The so-called endothelial cells, which line blood vessels, are essential for the health and growth of blood vessels that supply oxygen-rich and nutrient-loaded blood to organs and tissues. But as these endothelial cells age, blood vessels atrophy, new blood vessels fail to form and blood flow to most parts of the body gradually diminishes. This dynamic is particularly striking in muscles, which are heavily vascularized and rely on robust blood supply to function.

Muscles begin to shrivel and grow weaker with age, a condition known as sarcopenia. The process can be slowed down with regular exercise, but gradually even exercise becomes less effective at holding off this weakening.

Sinclair and team wondered: What precisely curtails the blood flow and precipitates this unavoidable decline? Why does even exercise lose its protective power to sustain muscle vitality? Is this process reversible?

In a series of experiments, the team found that reduced blood flow develops as endothelial cells start to lose a critical protein known as sirtuin1, or SIRT1. Previous studies have shown that SIRT1 delays aging and extends life in yeast and mice. 

SIRT1 loss is, in turn, precipitated by the loss of NAD+, a key regulator of protein interactions and DNA repair that was identified more than a century ago. Previous research by Sinclair and others has shown that NAD+, which also declines with age, boosts the activity of SIRT1.
A stimulating conversation 
The study reveals that NAD+ and SIRT1 provide a critical interface that enables the conversation between endothelial cells in the walls of blood vessels and muscle cells.
Specifically, the experiments reveal that in young mouse muscle, SIRT1 signaling is activated and generates new capillaries, the tiniest blood vessels in the body that supply oxygen and nutrients to tissues and organs. However, as NAD+/SIRT1 activity diminishes over time, the study found, so does the blood flow, leaving muscle tissue nutrient-deprived and oxygen-starved. 

Indeed, when researchers deleted SIRT1 in the endothelial cells of young mice, they observed markedly diminished capillary density and decreased number of capillaries, compared with mice that had intact SIRT1. Mice whose endothelial cells lacked SIRT1 had poor exercise tolerance, managing to run only half the distance covered by their SIRT1-intact peers.  
To determine SIRT1’s role in exercise-induced blood vessel growth, the researchers observed how SIRT1-deficient mice responded to exercise. After a month-long training regimen, the hind-leg muscles of SIRT1-deficient mice showed markedly diminished ability to form new blood vessels in response to exercise compared with same-age mice that had intact SIRT1 in their endothelial cells.

Exercise-induced blood vessel formation is known to occur in response to growth-stimulating proteins released by muscles under strain. SIRT1, however, appears to be the key messenger relaying growth-factor signaling from muscles to blood vessels, the study found.  

Experiments showed that endothelial cells lacking SIRT1 were desensitized to the growth-stimulating proteins released by exercised muscles.

“It’s as if these cells had grown deaf to the signals that muscles sent their way,” Sinclair said.

The observation, he added, explains why age-related loss of SIRT1 leads to muscle atrophy and blood vessel demise.

Since the experiments revealed the critical role of SIRT1 in exercise-induced blood vessel formation, the researchers wondered whether boosting SIRT1 levels would stimulate blood vessel growth and stave off muscle wasting.
Exercise in a pill?
The scientists set their sights on NAD⁺, a molecule conserved across many life forms, known to decline with age and previously shown to stimulate SIRT1 activity.
“We reasoned that declining NAD⁺ levels reduce SIRT1 activity and thus interfere with aging mice’s ability to grow new blood vessels,” said study first author Abhirup Das, who conducted the work as a post-doctoral fellow in Sinclair’s lab, currently a visiting scholar in genetics at Harvard Medical School and a post-doctoral research fellow at the University of South New Wales School of Medical Sciences. 
To test this premise, scientists used a chemical compound called NMN, a NAD⁺ precursor, previously shown to play a role in repairing cellular DNA and maintaining cell vitality.

In lab dish experiments, endothelial cells from humans and mice treated with NMN showed enhanced growth capacity and reduced cell death.

Next, the team gave NMN over two months to a group of mice that were 20 months old—the rough equivalent of 70 in human years. NMN treatment restored the number of blood capillaries and capillary density to those seen in younger mice. Blood flow to the muscles also increased and was significantly higher than blood supply to the muscles seen in same-age mice that didn’t receive NMN.
The most striking effect, however, emerged in the aging mice’s ability to exercise. These animals showed between 56 and 80 percent greater exercise capacity, compared with untreated mice the study showed. The NMN-treated animals managed to run 430 meters, or about 1,400 feet, on average, compared with 240 meters, or 780 feet, on average, for their untreated peers. 

To see whether the effects of NMN could be further augmented, the researchers added a second compound to the treatment regimen. The compound, sodium hydrosulfide (NaHS), is a precursor to hydrogen sulfide, which also boosts the activity of SIRT1. 
A group of 32-month-old mice—the rough equivalent to 90 in human years—receiving the combo treatment for four weeks were able to run, on average, twice as long as untreated mice. In comparison, mice treated with NMN alone ran 1.6 times farther, on average, than untreated animals.
“These are really old mice so our finding that the combo treatment doubles their running capacity is nothing short of intriguing,” said study co-author James Mitchell, associate professor of genetics and complex diseases at the Harvard T. H. Chan School of Public Health.  Research led by Mitchell and published in the same issue of Cell also found sodium hydrosulfide to augment blood vessel formation in the muscles of mice.

Interestingly, the NMN treatment did not improve blood vessel density and exercise capacity in young sedentary mice. However, it did boost blood vessel formation and exercise capacity in young mice that had been exercising regularly for a month.

“This observation underscores the notion that age plays a critical role in the crosstalk between blood vessels and muscles and points to a loss of NAD⁺ and SIRT1 as the reason behind loss of exercise effectiveness after middle age,” Das said.
The researchers say their findings may pave the way to therapeutic advances that hold promise for the millions of older people for whom regular physical activity is not an option.
“Even if you’re an athlete, you eventually decline,” Sinclair said. “But there is another category of people—what about those who are in a wheelchair or those with otherwise reduced mobility?”
The team’s ultimate goal is to replicate the findings and, eventually, move toward developing small-molecule, NMN-based drugs that mimic the effects of exercise—enhanced blood flow and oxygenation of muscles and other tissues. Such therapies may even help with new vessel growth of organs that suffer tissue-damaging loss of blood supply and oxygen, a common scenario in heart attacks and ischemic strokes, the team said.

Neo-vascularization—the formation of new blood vessels—should be treated with caution, the researchers say, because increased blood supply could inadvertently fuel tumor growth.
“The last thing you want to do is provide extra blood and nourishment to a tumor if you already have one,” said study co-author Lindsay Wu, at the University of New South Wales School of Medical Sciences.
Sinclair and Wu point out that experiments done as part of the current study provide no evidence that treatment with NMN stimulated tumor development in animals treated with the compound.
Co-investigators included George Huang, Michael Bonkowski, Alban Longchamp, Catherine Li, Michael Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto, Trevine-Villareal, Myung-Jin Kang, Tzong-tyng Hung, Brendan Lee, Eric Williams, Masaki Igarashi, James Mitchell, Nigel Turner, Zolt Arany and Leonard Guarente.

The work was supported by the Glenn Foundation for Medical Research (grants RO1 AG028730 and RO1 DK100263), and by the National Institutes of Health/National Heart, Lung and Blood Institute (grant RO1 HL094499).
Relevant disclosures:
Sinclair and Wu are consultants and inventors on patents licensed to Metro International Biotech, JumpStart Fertility, Vium, Life Biosciences and Liberty Biosecurity. Sinclair is consultant to EdenRoc Sciences, Arc Bio, Segterra, Animal Biosciences, Senolytic Therapeutics, Spotlight Biosciences and Continuum Biosciences. Wu is consultant to Intravital and JumpStart Fertility. Bonkowski is a consultant to Metro International Biotech. Sinclair sits on the fiduciary board and has an equity interest in EdenRoc Sciences, Arc Bio, Segterra, Metro International Biotech, Liberty Biosecurity, Animal Biosciences, Life Biosciences, Senolytic Therapeutics, Spotlight Biosciences and Continuum Biosciences. He is a cofounder of EdenRoc Sciences, Arc Bio, Metro International Biotech, Liberty Biosecurity, Life Biosciences, and Spotlight Biosciences. Guarente is advisor to Segterra, Sebelius and Elysium Health. A provisional patent application has been submitted with Das, Wu and Sinclair as inventors.
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It’s gained a lot of attention for its reported anti-aging and disease-fighting powers. Researchers have long believed that substances in red wine might have health benefits. Beginning in the 1990s, experts began to focus on resveratrol, an antioxidant compound in red wine. Since then, some animal and lab studies have shown that resveratrol has promising antiviral, anti-inflammatory, and anticancer effects.
It’s important to note that while experts agree that it does have potential, there’s still not enough data to confirm how well it works. Resveratrol supplements have not been well-studied in people. We don’t really know what benefits and risks they might have. We also don’t know if resveratrol is necessarily more important than some of the other natural substances in wine.
Still, early research does suggest it might help protect you against:
Heart disease: It’s thought to help reduce inflammation, lower LDL or “bad” cholesterol, and make it more difficult for clots to form that can lead to a heart attack.
Cancer: It could limit the spread of cancer cells and start killing them.
Alzheimer’s: It may protect nerve cells from damage and fight the plaque buildup that can lead to the disease.
Diabetes: Resveratrol helps prevent insulin resistance, a condition in which the body becomes less sensitive to the blood sugar-lowering hormone insulin. The condition can lead to diabetes.
Researchers believe that resveratrol activates the SIRT1 gene. That gene is believed to protect the body against the effects of obesity and the diseases of aging.
Some people wonder if they should drink more red wine because of the possible health benefits of resveratrol. But most experts and organizations like the American Heart Association still suggest limiting alcoholic drinks to one per day for women and two for men. Four ounces of red wine equals one drink. Other forms of alcohol do not have resveratrol.
So far, studies have not discovered any severe ones, even when resveratrol is taken in large doses. When you get resveratrol in the amount naturally found in foods, it is generally considered safe. It could cause a reaction in those who are allergic to grapes or wine.
People who have health conditions like bleeding disorders should not take resveratrol without talking to a doctor first.
If you take any medicines or other supplements regularly, talk to your health care provider before you start using resveratrol supplements. They could interact with medicines like blood thinners, blood pressure drugs, cancer treatments, MAOI antidepressants, antiviral and antifungal medicines, NSAID painkillers, and supplements like St. John’s wort, garlic, and ginkgo.
As with other supplements, the FDA doesn’t regulate resveratrol. That makes it hard for consumers to know exactly what they’re getting or whether the product is effective. There also isn’t any specific dosage recommendation, and how much you should take can vary from supplement to supplement.
The dosages in most resveratrol supplements are typically much lower than the amounts that research has shown to be helpful. Most supplements contain 250 to 500 milligrams. To get the dose used in some studies, people would have to consume 2 grams of resveratrol (2,000 milligrams) or more a day. Ask your doctor for advice.
Until more high-quality research is done, experts do not recommend resveratrol supplements for antiaging or disease prevention. Resveratrol supplements are also not recommended for children or for women who are pregnant or breastfeeding.
SOURCES:
Brown, L. Alcoholism: Clinical and Experimental Research, 2009.
Linus Pauling Institute: “Resveratrol.”
Baur, J.A. Nature, 2006.
Barger, J.L. PLoS One, 2008.
Memorial Sloan-Kettering Cancer Center: “Resveratrol.”
Van der Spuy, W.J. Nutrition Research Reviews, Sept. 22, 2009.
Karuppagounder, S.S. Neurochemistry International, 2009.
American Heart Association: “Alcohol, Wine and Cardiovascular Disease.”
Fundukian, L., ed. The Gale Encyclopedia of Alternative Medicine, third edition, 2009.
Natural Medicines Comprehensive Database: “Resveratrol.”
Natural Standard Patient Monograph: “Resveratrol.”
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Symptoms and causes.
20 foods to add to your diet right now.
Top tips for taking them safely.
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WebMD does not provide medical advice, diagnosis or treatment.
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Top NAD+ Supplements for 2021

Our editorial team contacted manufacturers, checked lab reports, and personally tested the best NAD+ boosters available today. Here are our rankings of the best NAD+ supplements for 2021.

Tru Niagen

Tru Niagen is one of the best-known NAD+ boosters on our list – and for a good reason. The supplement helps drive cellular energy production and promotes cellular repair using 500mg of Niagen nicotinamide riboside (NR) per capsule. By taking one capsule of Tru Niagen daily, you can purportedly increase NAD+ by 80%, according to studies that used 100mg, 300mg, and 1,000mg daily doses of Niagen NR.
Tru Niagen is available in concentrations of 300mg and 500mg. Many people take Tru Niagen daily to affect cellular energy, aging, and overall health and wellness. You can also buy 30 count, 90 count, or 180 count bottles of Tru Niagen. The more you buy, the more you save. As one of the few NAD+ boosters on this list backed by specific scientific evidence, Tru Niagen is one of the NAD+ supplement space leaders.

• Tru Niagen Price: $40 to $230

Cymbiotika NMN

Cymbiotika’s NMN is another popular and well-known NAD+ booster supplement available today. Priced under $80 per bottle, Cymbiotika NMN gives your body nicotinamide mononucleotide (NMN), the direct precursor of NAD+ and a key component for raising NAD+ levels within your body.
Each capsule of Cymbiotika NMN contains NMN and complementary ingredients like apigenin, green tea extract, resveratrol, and green coffee bean. By giving your body antioxidants, polyphenols, nutrients, and precursors, Cymbiotika NMN could boost NAD+ levels within the body. Cymbiotika recommends taking two capsules daily to support energy revitalization, protection from aging, healthy DNA protection, cognitive health, and other effects.

• Cymbiotika NMN Price: $77

Elysium

Elysium was one of the forerunners of the NAD+ booster space. The supplement features a clinically proven B-vitamin complex patented by Oxford to slow brain atrophy as you age. In one study, the B-vitamin complex slowed age-related grey matter atrophy in regions associated with learning and memory by 86%.
In addition to the unique B vitamin complex, Elysium contains omega-3 fatty acids, anthocyanins, and antioxidants with enhanced bioavailability. Plus, to test the supplement’s effects, Elysium lets you buy a biological age test kit. Take Elysium daily, then test your age with the kit before and after taking the supplement. Elysium can support anti-aging effects and help you turn back the clock.
Elysium offers two core NAD+ supplements, including Matter (for long-term brain health) and Basis (for general anti-aging and DNA health). Elysium is also one of the few NAD+ booster supplements on this list backed by actual clinical trials in humans.

• Elysium Price: $50 to $70

RiboGEN

RiboGEN is a nicotinamide riboside (NR) supplement that contains 300mg of NR per serving. The makers of RiboGEN claim their formula is the only pharmaceutical-grade supplement that uses the same purity of NR used in medical research and clinical studies.
The NR in RiboGEN works similarly to the NR used in other NAD+ supplements listed here: it’s a precursor to NAD production, giving your body the ingredients it needs to produce NAD, leading to higher NAD+ levels. With 99.5% concentration of nicotinamide riboside and 0.5% NAM, RiboGEN is a no-nonsense NR supplement linked to potential NAD+ boosting effects.
At $330 per bottle, RiboGEN seems more expensive than competing NAD+ boosters on this list. However, each bottle contains 300 capsules (300 servings), making RiboGEN’s pricing compared to other supplements on this list.

• RiboGEN Price: $330

Life Extension NAD+ Cell Regenerator

Life Extension tells you what their supplement is meant to do directly within the name: the supplement is designed to regenerate cells by promoting NAD+ production. Like specific NAD+ boosters listed here, Life Extension NAD+ Cell Regenerator contains a 300mg dose of Niagen NR. Life Extension has added trans-resveratrol to every dose to supplement the effects further, leading to higher NAD+ levels.
According to Life Extension, NAD+ Cell Regenerator can help fight fatigue on a cellular level, promote mitochondrial health, and support youthful cellular energy production, among other effects. And, at $45 per bottle, it’s one of the better-value NAD+ boosters on this list, offering similar ingredients to other NAD+ boosters but at a discount rate.

• Life Extension NAD+ Cell Regenerator Price: $45

Science.bio NR Chloride Powder

Science.bio offers one of the most potent nicotinamide riboside (NR) supplements on this list. Science.bio’s NR Chloride Powder available in 10g jars for under $30. You can mix the powder as needed – or put it in your own capsule – to enjoy the potential NAD+ boosting benefits.
Each batch of Science.bio’s NR Chloride Powder is batch and lot-coded with publicly visible lab reports to ensure quality and transparency. The jar is also protected against UV to minimize degradation. That means you get the highest possible dose of nicotinamide riboside – all without the filler ingredients seen in other NAD+ booster formulas sold online today.

• Science.bio NR Chloride Powder Price: $30

Alive By Science

Alive By Science offers several NAD+ boosters, including unique liposomal gels that work differently from any other supplement on this list. Alive By Science is best-known for its NAD+ with Resveratrol LIPO Gel and its NMN with Resveratrol LIPO Gel. Priced at $75 to $80 per bottle, the gels are designed for sublingual use (underneath the tongue) for maximum absorption).
Alive By Science also offers powdered NMN and NAD+ supplements, allowing you to enjoy the benefits of NMN and NAD+ supplementation in convenient capsulated form. Alive By Science may have the right NAD+ boosters for your unique anti-aging needs with multiple options for all tastes and preferences.

• Alive By Science Price: $50 to $80

Quicksilver Scientific Liposomal NAD+ Gold

Quicksilver Scientific offers a popular NAD+ booster supplement called NAD+ Gold. The supplement claims to boost NAD, leading to healthy aging, cognition, and energy. Like the Alive By Science NAD+ boosters above, Quicksilver Scientific’s NAD+ Gold uses liposomal delivery for superior bioavailability, which means more active ingredients end up in your bloodstream.
To take NAD+ Gold, just press two pumps into your mouth and hold them for 30 seconds. Then, swallow. The formula contains precursors to NAD+ (including NMN), helping to raise NAD+ levels within the body. At $60 for a high-powered liquid tincture, Quicksilver Scientific is one of the top-rated NAD+ booster companies available today.

• Quicksilver Scientific Liposomal NAD+ Gold Price: $60

HPN Supplements NAD3 NAD+ Booster

HPN Supplements offers an NAD+ booster called NAD3. Advertised as a “fountain of youth,” the formula delivers 311mg of a unique formula per serving. While other NAD+ boosters use NR or NMN, HPN supplements have taken a different approach: the company has created a proprietary blend called its NAD3 Patent-Pending Formula. That formula includes theacrine, wasabi, and copper nicotinic acid, all of which can purportedly boost NAD+ levels.
By taking NAD3 daily, you can purportedly increase telomerase activity for aging, help reduce cellular inflammation, activate NRF2 for cell detoxification, and boost NAD+ for mitochondrial function, among other benefits. Plus, with 60 servings for $60, it’s one of the better-value NAD+ boosters on our list.

• HPN Supplements NAD3 NAD+ Booster Price: $60

Toniq NMN

Toniq’s NMN may have some of the best-looking packages on this list. The no-nonsense packaging is what you would expect when dealing with a no-nonsense NMN-based NAD+ booster. Each bottle contains 99% pure NMN that can give your body the precursors it needs to produce more NAD+.
Despite being a high-quality NAD+ supplement with 60 servings per bottle, Toniq NMN is priced at just $45 per bottle. You can save even more with the larger bottle featuring 180 capsules. By taking Toniq NMN daily, you can purportedly give your body high-quality nicotinamide mononucleotide (NMN) in each serving, helping you support NAD+ production within your body.

• Toniq NMN Price: $110

Liftmode NMN

Liftmode’s NMN contains 10g of nicotinamide mononucleotide per bottle. Unlike NR, NMN is not a variant of vitamin B3. Instead, it’s a synthetically produced nucleotide that, like NR, is linked with anti-aging effects through its effects on NAD+ levels. Each jar of Liftmode NMN contains 10g of pure NMN, making it easy to customize your dose however you like.
According to Liftmode, the Liftmode NMN formula can promote healthy cellular energy levels, provide powerful regenerative effects, sharpen cognitive function in the aging brain, and provide other benefits. Plus, Liftmode uses a transparent, sealable plastic jar to maximize purity and potency.

• Liftmode NMN Price: $68

How We Ranked the Top NAD+ Supplements for 2021

Every NAD+ booster claims to raise NAD+ levels while supporting anti-aging benefits. However, only the best NAD+ supplements live up to the hype.
To separate the best and worst NAD+ boosters available today, we used the following ranking factors:

Proven Ingredients

The two most proven ingredients for boosting NAD+ are NR and NMN. All of the top-ranked NAD+ boosters use one of these two ingredients. They’re both precursors to the production of NAD+. The more clinically proven ingredients an NAD+ booster used, the higher we ranked it.

Strong Doses

NAD+ booster supplements may contain the right ingredients – but at weak dosages. After verifying each NAD+ booster had the right ingredients, we made sure they used effective doses of those ingredients.

Transparency

Some NAD+ boosters use proprietary formulas or hide their ingredient labels, making it difficult to verify what’s inside each formula. We preferred NAD+ boosters with transparent and honest ingredient labels that took all guesswork out of the supplement.

Complementary Ingredients

Boosting NAD+ isn’t an exact science. Studies show that turmeric, resveratrol, and other ingredients could boost NAD+ in specific ways, which is why many NAD+ boosters contain these ingredients. We considered complementary ingredients in our rankings, although we did not punish companies with no complementary ingredients.

Manufacturer Reputation

Niagen, Cymbiotika, and Elysium are three of the best-known and most reputable brands in the NAD+ booster space. They have a long history of producing high-quality NAD+ booster supplements. Some of the top companies have even invested in human clinical trials. We preferred manufacturers with a proven reputation over those looking to make a quick buck from the hype of NAD+ supplements.

Price & Value

Some people want to spend $30 on an NAD+ booster supplement. Others want to spend $200. We featured NAD+ boosters across a range of different prices. However, we emphasized good value at each price to ensure your investment was not wasted with any of the top-ranked NAD+ supplements listed above.

Advertised Benefits

Some NAD+ booster companies exaggerate their benefits, claiming their supplement can reverse your age by 20 years or help you lose 50lbs in a month. We were wary of NAD+ booster companies advertising benefits like this, and we preferred companies with more honest advertised benefits.

Human Clinical Trials

Some of the best NAD+ booster supplements on our list are backed by human clinical trials. Companies have invested in trials on humans to verify their supplement works as advertised—the more scientific evidence supporting an NAD+ booster, the better.

Top 4 Benefits of NAD+ Boosters

Many people take NAD+ boosters daily for their purported benefits. A good NAD+ booster supplement could support all of the following benefits:

Combat Age-Related Memory Loss

As you get older, your memory naturally declines. NAD+ is vital for repairing DNA and resisting neuronal stress. Many people find their memory and recall improve after taking an NAD+ booster.

Weight Loss

Studies show that NAD+ boosters could help counter the effects of high-fat diets and make it easier to manage weight. In one study, mice receiving a high-fat diet gained 60% less weight while taking an NR supplement than a placebo group. These mice also had higher energy levels.

Reverse the Effects of Aging

Many people take NAD+ boosters to reverse the effects of aging. While NAD+ boosters won’t make you younger overnight, studies suggest they could help your body manage the specific effects of aging. In one study, for example, researchers gave NAD+ boosters to mice. After one week, researchers were unable to determine the difference between tissues collected from four-month-old mice and tissues collected from two-year-old mice that had received the NAD+ booster. In other words, the NAD+ booster seemed to reverse the effects of aging.

Boost Muscle Strength and Endurance

Some take NAD+ boosters for exercise performance. Studies show that taking an NAD+ booster can boost muscle strength, enhance endurance, and provide other benefits. Studies have linked NAD+ boosters to DNA repair, muscle growth, and improvements in endurance at the cellular level, among other effects.

Top 5 Natural Ways to Boost NAD+ Levels

You can optimize NAD+ levels without taking an NAD+ supplement.
Some people take an NAD+ booster to support healthy NAD+ levels in the body. However, studies show that changing diet and lifestyle habits can also impact NAD+.
Here are five of the most proven natural ways to boost NAD+ levels, according to science:

Restrict Calories

According to some studies, eating just 20% to 30% fewer calories than usual can boost NAD+ production.

Fast or Practice Intermittent Fasting

Fasting can raise NAD+ levels within your body. Studies show that a combination of fasting and calorie restriction can increase NAD+ production in the body, boosting longevity and supporting healthy aging.

Avoiding Sun Damage

When your skin is damaged by the sun, your body sends NAD to repair the damage. That means the NAD isn’t available for use elsewhere on the body. Wearing sunscreen or protective clothing can minimize damage and preserve NAD+.

Practice HIIT Workouts

Studies show that high-intensity interval training (HIIT) can boost growth hormone, NAD+ levels, and other effects. We’ve known that HIIT-type workouts can boost the health of your mitochondria, but growing research suggests these workouts can also increase NAD+ levels – or at least help your body use NAD+ more efficiently.

Follow a Healthy Diet

If your body isn’t getting the vitamins, minerals, and nutrients it needs, it struggles to produce many crucial compounds – including NAD+. Follow a healthy, balanced diet to optimize NAD+ levels and control specific effects of aging.

Top 5 Best Foods for Boosting NAD+ Levels

Studies have shown that some foods can boost NAD+ levels. You can fast, restrict calories, and follow a keto diet to boost NAD+ levels. You can also eat the following types of food:

• Milk: Dairy milk is a good source of nicotinamide riboside (NR). Drinking a glass of milk daily could help you feel younger and healthier.
• Fish: Fish are rich with precursors to NAD+, which is why many people eat tuna, salmon, and sardines daily for anti-aging effects.
• Mushrooms: Mushrooms can help naturally boost NAD levels. By adding multiple types of mushrooms to your diet, you may be able to optimize anti-aging effects.
• Green Vegetables: Green vegetables are rich in vitamins, minerals, and nutrients your body needs to produce NAD+ and other crucial compounds.
• Yeast & Whole Grains: Whole grains are rich in vitamin B3, including vitamin B3 that you won’t find in processed grains. Similarly, yeast contains nicotinamide riboside, which is a precursor to NAD. The next time you need to boost NAD+ levels, consider visiting your local bakery.

Side Effects of NAD+ Boosters

Most healthy adults will experience no significant side effects associated with NAD+ booster supplements.
Like other supplements sold online today, NAD+ boosters contain doses and ingredients generally recognized as safe (GRAS) by the FDA. These ingredients have been proven to be safe for most people when following the recommended dosage instructions.
However, if you are taking any medication or have a medical condition, you should talk to your doctor before taking an NAD+ booster supplement or any other supplement.

NAD+ Booster Dosage

Most NAD+ boosters contain a dose of around 300mg of NR or an equivalent dose of NMN.
Most studies have verified that this dose can meaningfully raise NAD+ levels within the body. Some studies have shown that doses as small as 100mg can have similar effects. Some studies also use doses of 1,000mg to enhance the effects of NAD+ even further.
As more studies get released on NMN, we’re learning more about the equivalent dosage of NMN to boost NAD+.
Overall, you should look for an NAD+ booster supplement with a minimum of 300mg of NR per serving to optimize NAD+ boosting effects.

Scientific Evidence for NAD+ Boosters

NAD+ boosters are a new type of supplement. However, growing research has validated certain NAD+ booster benefits, and researchers believe NAD+ boosters could provide powerful anti-aging effects throughout the body. However, more research is needed to verify these effects – especially largescale research in humans.
In this animal study, researchers gave an NR supplement to a group of mice that had been specifically bred to develop human-like age-related memory decline. Some mice took an NR supplement in their drinking water for three months, while other mice took a placebo. Mice in the NR group had less DNA damage, higher neuroplasticity, increased production of new neurons, lower neuronal damage, and less DNA damage in the hippocampus (hippocampus damage is associated with memory issues), among other benefits.
Meanwhile, this study on mice found that NAD+ boosters could counteract the effects of a high-fat diet. Mice received a high-fat diet combined with an NR supplement or a placebo. Mice taking the NR supplement gained 60% less weight than mice taking the placebo. These mice also had higher energy levels and improved oxidative metabolism, among other effects.
Taking an NR supplement to raise NAD+ levels could also help with muscle function and strength. As you get older, you lose muscle function and strength. In this study, researchers gave mice an NR supplement or a placebo and observed better strength and exercise gains in the NR group than in the placebo group.
Many people also take NAD+ boosters for their purported ability to repair DNA. Repairing DNA may sound like a vague and poorly defined benefit. However, some studies have validated the ability of NAD+ boosters to repair DNA. For example, in one study, NAD+ precursor supplementation led to increased DNA repair and improvements in muscle tissue health within just a week. In that study, researchers were unable to determine the difference between two-year-old mouse tissues and four-month-old mouse tissues, suggesting NAD+ precursors (like NR and NMN) could turn back the clock on aging.
Other studies have shown that NAD+ boosters promote longevity by increasing the activation of SIRT1, a type of sirtuins protein. In this study on mice, for example, researchers found that NR supplementation increased the lifespan of mice by improving mitochondrial function.
You don’t have to take an NAD+ booster supplement to boost NAD+ levels. Instead, studies show that fasting, reducing caloric intake, and making other diet and lifestyle changes could increase NAD+ levels significantly.
In this 2014 study, for example, researchers found that eating 20% to 30% fewer calories than usual was associated with higher NAD+ levels. Similarly, this study showed that fasting and caloric restriction increased NAD+ levels and increased the activation of SIRT1, potentially leading to an increased lifespan. For these reasons, many people claim that keto dieting and intermittent fasting programs can raise NAD+ levels, although more research is needed to verify these benefits.
Although many NAD+ studies have involved mice instead of humans, there have been multiple human trials. For example, in this study, researchers found that NR supplements safely and effectively increased NAD+ levels in a group of healthy adults. Similarly, this study published in Nature Communications found that NR supplementation significantly boosted levels of both NAD+ and adenine diphosphate ribose (ADPR).
Ultimately, more science is needed to validate the effects of NAD+ boosters and supplements. However, growing research in mice, animals, and humans shows that NAD+ boosters could be some of the most effective types of anti-aging supplements ever released.

FAQs About NAD+ Boosters

Q: What is NAD?

A: NAD (nicotinamide adenine dinucleotide) is a coenzyme found in all cells. It plays a crucial role in cell metabolism. The coenzyme exists in two primary forms, including NAD+ and NADH.

Q: What’s the difference between NAD, NAD+, and NADH?

A: NAD is a coenzyme found in all cells that plays a vital role in cell metabolism. The coenzyme exists in two forms, including NAD+ (the form of NAD that serves all functions throughout the cell) and NADH (the form occupied by electrons and unable to perform all processes throughout the cell).

Q: What does NAD+ do?

A: NAD+ plays a critical role in multiple aspects of cell metabolism, including the transformation of nutrients we eat into adenosine triphosphate (ATP), which is the fuel your cells use to exchange and produce energy.

Q: What is ATP?

A: Adenosine triphosphate (ATP) is the energy used by your cells. NAD+ helps turn the nutrients you eat into ATP, allowing your cells to exchange and produce energy.

Q: What are sirtuins?

A: Sirtuins are proteins that play a crucial role in multiple cell processes, interacting with NAD+ while playing a vital role in cellular energy. NAD+ and sirtuins help with gene expression, chromosomal maintenance, DNA repair, mitochondria preservation and stimulation, and other effects.

Q: Why does NAD drop with age?

Q: Your body must continuously produce NAD to ensure cellular health and energy. However, as you get older, your body naturally produces less NAD.

Q: What are the symptoms of low NAD levels?

A: When you have low NAD levels, your cells have a reduced ability to make and use ATP energy. You could feel lethargic. You might not feel as physically or cognitively active as you used to be. NAD is crucial for cellular function and cellular energy, and you could feel complex effects at every level of your body.

Q: How does a NAD supplement help?

A: Recent studies have shown that adding NAD directly to cells can reduce specific effects of aging. Researchers have added NAD directly to cell cultures and observed mouse cells turning back the clock to become identical to younger mouse cells. Today, NAD supplements claim to use similar processes to reduce cellular stress, age-related stress, and cell aging.

Q: What is a NAD booster?

A: An NAD booster or NAD+ booster is a supplement that claims to target NAD within your body. As you get older, your NAD levels drop, leading to various symptoms of aging. NAD+ boosters claim to counteract these effects, restoring your body’s NAD+ levels and giving you back your cellular energy.

Q: What is nicotinamide riboside (NR)?

Q: Nicotinamide riboside (NR) is one of two significant precursors to NAD biosynthesis. Studies show that your body uses NR to produce NAD+. That’s why many NR supplements are considered NAD+ boosters.

Q: What is nicotinamide mononucleotide (NMN)?

A: Nicotinamide mononucleotide (NMN) is one of two significant precursors to NAD biosynthesis. Your body uses NMN to produce NAD+, which could impact cellular energy.

Q: What’s the difference between NAD+ boosters that use NMN and NR?

A: The NAD+ supplement industry is new, and studies continue to compare NMN and NR supplements. Both NMN and NR are considered precursors to NAD synthesis within the body, which means they could raise your body’s levels of NAD (leading to higher NAD+ levels). As more research continues, we’re learning more about the difference between NR and NMN supplements.

Q: How do I increase NAD levels naturally?

A: Studies show that NAD is connected to diet and exercise habits, fat burning, and more. Diets high in fats and low in carbs, for example, may increase the ratio of NAD+ to NADH, protecting your body from oxidation and maximizing anti-aging effects. Others practice intermittent fasting to increase NAD levels naturally. Some take NAD+ supplements.

Q: Does HIIT boost NAD+?

A: Studies show that high-intensity interval training (HIIT) workouts could raise NAD+ levels. Exercising at a high level of intensity for brief periods can boost growth hormone production, NAD+ levels, and other elements linked to aging.

Q: Why can’t I just take an NAD+ supplement with NAD+?

A: NAD+ boosters contain NR or NMN, both of which are precursors to NAD+. Why? Studies show that NAD+ is too large to permeate cellular walls. You can’t just eat a spoonful of NAD+ to raise NAD+ levels. It doesn’t work that way. An NAD+ capsule would be too big to swallow, which is why all NAD+ boosters come in the form of NR and NMN supplements.

Q: Do niacin supplements boost NAD+?

A: Niacin, also known as nicotinic acid, is a type of vitamin B3 shown to increase NAD+ levels. Although it’s not been shown to be as powerful as NR or NMN, it could still raise NAD+ levels in a significant way.

Q: Is NR better than NMN for boosting NAD+?

A: Most studies on NAD+ boosters use NR instead of NMN. Some believe NMN, like NAD+, is too big for your body to absorb. The three most minor versions of vitamin B3, including niacin, nicotinamide, and NR, are the smallest precursors of NAD+ that can permeate your cell walls.

Q: What are the side effects of NAD+ boosters?

A: Most healthy adults experience no side effects from NAD+ boosters. However, NAD+ boosters with high levels of niacin can lead to reddened skin, a burning sensation, and itching in rare cases.

Q: What are the best foods for boosting NAD+?

A: Studies show that dairy milk, fish, mushrooms, and yeast can boost NAD and NAD+ levels within the body.

Q: Is sunlight harmful for NAD+ production?

A: Your body needs NAD+ to repair some of the damage done by sunlight. Excessive sunlight exposure can deplete levels of NAD+ within your body. Your body uses NAD+ to repair cells damaged by UV radiation. If you have sun damage, your body uses NAD+ to repair this damage instead of using it elsewhere.

Q: What are the benefits of NAD+ boosters?

A: NAD+ supplements claim to help restore muscle strength and stamina, boost energy levels, protect your liver, strengthen your immune system, help with sleep/wake cycles, maintain mental sharpness, and encourage DNA self-repair, among other benefits.

Q: Why are low NAD levels wrong?

A: Low NAD levels are associated with cell death, cardiovascular disease, weight gain, decreased metabolism, impaired brain function, and other effects.

Q: How does NAD IV therapy work?

A: Some people take NAD supplements to boost NAD+ levels. Others take NAD through intravenous (V) injection. Health professionals inject NAD and complementary vitamins directly into your bloodstream to deliver targeted benefits.

Q: What is the best NAD+ supplement?

A: Niagen, Elysium, and Cymbiotika are three of the best-known and best-rated NAD+ booster supplement brands available today.

Top NAD+ Supplements for 2021 Final Word

Nicotinamide adenine dinucleotide (NAD) is crucial for cellular energy. By taking an NAD+ booster supplement, you can optimize levels of NAD+ within the body, which can boost cellular energy, endurance, cognition, and even weight loss, among other effects.
With so many NAD+ boosters promising similar things, it helps to sort through the hype to discover the quality below. The NAD+ booster supplements listed above are some of the top-ranked NAD+ supplements available today.
Affiliate Disclosure:
The links contained in this product review may result in a small commission if you opt to purchase the product recommended at no additional cost to you. This goes towards supporting our research and editorial team and please know we only recommend high quality products.
Disclaimer:
Please understand that any advice or guidelines revealed here are not even remotely a substitute for sound medical advice from a licensed healthcare provider. Make sure to consult with a professional physician before making any purchasing decision if you use medications or have concerns following the review details shared above. Individual results may vary as the statements made regarding these products have not been evaluated by the Food and Drug Administration. The efficacy of these products has not been confirmed by FDA-approved research. These products are not intended to diagnose, treat, cure or prevent any disease.

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