My life with the Leonards: What I learned from two brilliant scientists

My life with the Leonards: What I learned from two brilliant scientists David A. Sinclair Ph.D., A.O.Click here to view David A. Sinclair Ph.D., A.O.’s profile David A. Sinclair Ph.D., A.O. Professor at Harvard Medical School and Co-Host of the Lifespan Podcast Published Aug 1, 2018 + Follow If you've spent much time with me, you know I don't mind a bit of name dropping. A few months back, I had the opportunity to dine with Sen. Elizabeth Warren. I brought my eldest child, Alex, with me—and the inspiration that happened at that table was absolutely priceless. I've hung out with Pink (That bought me some cred with my kids, at least for a bit.) And a few years ago, at the Time 100 Gala, I was a cocktail away from asking Amy Adams to dance. I can go on. Would you like to hear me go on? No? Oh... OK. That's fine. Not really the point anyway. The point is that even though my line of work puts me in contact with some pretty nifty people—singers, athletes, billionaires, political leaders and famous mad scientists—the names I most often drop into conversation are two guys that many people have never heard of. But those two guys—both named Leonard, as it happens—have been incredibly influential to me. The first Leonard is Lenny Guarente, a biologist at the Massachusetts Institute of Technology whose work on lifespan extension in yeast, roundworms and mice has come second only to his dedication to developing the next generation of scientists. He's one of the most independent thinkers and rebellious intellectuals you'll ever meet. The alumni of Lenny's lab comprise a "who-is-who" of international aging science, and I'm lucky to say I am one of the fortunate few who got to spend time with Lenny at MIT. From Lenny Guarente I learned something vital: Great scientists forge their own paths. It's easy to be a follower in this world. It's easy to do work that is derivative. It's easy to push the ball a tiny way down the field. Lenny demanded more than that from the researchers in his lab. He told us to swing for the fences. The second Leonard is Leonard Hayflick, who decades ago designed a simple but clever experiment to test whether cells’ limited capacity to replicate in culture was caused by microbial contamination or some unknown culture condition. At the time, it had only recently been shown that female cells could be distinguished from male cells by the presence of Barr bodies (formed by condensed inactive X chromosomes.) Using Barr bodies as a guide, Leonard discovered that, after a series of reproductions, only female cells remained, showing that replication ceased "not because of some extrinsic factor," he would later explain, "but because of an intrinsic cell phenomenon—a revolutionary idea at the time." The idea was so revolutionary, in fact, that it was rejected by The Journal of Experimental Medicine before being accepted for publication in Experimental Cell Research in 1961. What's more, the rejection came from Francis Peyton Rous who was already scientific royalty and went on to win a Nobel Prize a few years later. From Leonard Hayflick, I learned something that has helped steel me for the challenges that have come from forging my own path the way Lenny Guarente demanded: Never give up on what you believe. I don't always see eye-to-eye with either of the Leonards. Lenny Guarente and I were once described as being engaged in a "bitter dispute" that was nothing short of a "family feud." (It wasn't really anything like that, but we have published dueling papers and have been engaged in the very sort of spirited competition that drives science forward.) Leonard Hayflick has been an outspoken critic of efforts to extend human lifespans, and has gone so far as to say that aging is not a disease; I obviously disagree. Last week, I was chatting with some undergraduates at Harvard, who deeply impressed me with their interest in and insights about aging research, and especially with the tough questions they asked about the social and environmental implications of my work. Later, over a beer with a friend, I reflected on how nice it was to think they might one day engage in their own bit of name dropping—with me! "Oh, they'll do that," my friend said. "They'll tell all their friends about the time they disagreed with you in front of a classroom of fellow students." Yeah, I think I'm OK with that. --- Hey there. I'm writing a book about the past, present and future fight to slow, stop and reverse aging. Want to help me name it? Head over to Twitter—I'm @davidasinclair—and give me your suggestion! Introducing Lifespan - The Book About Why We Age & Why We Don't Have To David A. Sinclair Ph.D., A.O.Click here to view David A. Sinclair Ph.D., A.O.’s profile David A. Sinclair Ph.D., A.O. Professor at Harvard Medical School and Co-Host of the Lifespan Podcast Published Sep 10, 2019 + Follow The blurb that blurbed me When Siddhartha Mukherjee called my book, “an elegant and exciting book that deserves to be read broadly and deeply," I didn’t know how to react. These were the words of an absolutely brilliant physician, biologist and oncologist, for goodness sake, from an author who won the Pulitzer Prize for non-fiction. His book, “The Emperor of All Maladies: A Biography of Cancer” was formative in some of the ideas and the writing style of “Lifespan: Why We Age — and Why We Don’t Have To.” “Lifespan” challenges the idea that cancer reigns supreme over all other diseases—because, as you may have heard, I have argued that aging itself is a disease, and that it is, in fact, the key driver of other diseases, including cancer. So, when I saw those words in my inbox, a few months ago, I was stunned and humbled. And, I’ve got to admit: I was also excited. Because if Siddhartha Mukherjee thinks this book deserves to be read, maybe it really does. Visit Lifespanbook.com to order the book today If you know me, you know that I’m a generally confident guy who doesn’t like to be told what to do. That’s in part the Aussie in me. It’s also the result of being very fortunate to have had mentors, colleagues, collaborators and students who have pushed me to be my very best. I’ve always thought this book was important, that an awakening to the true nature of aging is underway, and that the proffering of a unified theory of aging was a vital step toward a better future. But, at the same time, I’ve been immersed in it for years, and I know that being completely surrounded by something is a good way to lose sight of the horizon. And so, to be honest, I was worried that I might miss the mark. Not when it comes to the science, but in the way I’ve presented it. Would my humor fall short? Would the stories seem self-indulgent? Would some people find the book too complicated and give up on it altogether? Would others wish I’d not gone deep enough? Then that amazingly kind “blurb” landed in my inbox. And then, after that, another came from Leroy Hood, the famous biologist, and National Medal of Science recipient, whose work in DNA sequencing has been instrumental in driving forward many of the greatest advances in science of the past 40 years. “There are few books that have ever made me think about science in a fundamentally new way,” Hood wrote. “David Sinclair’s book did that for me on aging.” Wow. Just. Wow. The blurbs kept coming. From Mark Hyman and Dean Ornish. From William Li and Dale Bresden and Sara Gottfried. These are all people who have written books that fundamentally changed the way other people think about health and science. It was all so incredibly humbling. And also, it was confidence-boosting. Look, I still don’t know how this book will be received when it “hits the streets.” I’m told that some books that seem destined for best-seller status fizzle out when people crack the bindings, while others that seemed to be destined for the dollar bin wind up selling millions of copies. I don’t really know what other people’s expectations for this book are. But for me, it comes down to this: I believe you’ll find this book to be exciting. I believe this book will challenge your ideas about aging. I believe this book will make you think about your own life and your future — and the future of our species on this planet — in a different way. Indeed, today, as this book is put out on shelves and as it arrives in people’s mailboxes around the world, I’m feeling confident about all of that. I hope you will agree. __________________________________________________________________________ By David Sinclair on September. 10th, 2019 I have lots of weird ideas. Some of them turn into research questions. Others turn into companies. Some simply get tweeted, and that's the end of that. Head over to Twitter — I'm @davidasinclair — to find out what's on my mind. Order Lifespan here. 529 109 Comments Like Comment Share Muneera Salem-Murdock Muneera Salem-Murdock I do agree. I'm trying to find out if it's been translated into French to recommend to my Francophone friends. I've been reading it the last couple of days and almost done. Mind-blowing. Like Reply 1 Like 2mo Kevin Cranfield Kevin Cranfield Thanks David for the research and book - great to listen to on audible - I look forward to following more developments in this area Like Reply 5mo Emma Torkington Emma Torkington This is one of my favourite books. It was a fascinating read and beautifully written too. Thank you! Like Reply 1y Vania Assaly Vania Assaly Congratulations for your publication I´m looking forward read all the ideas inside it Best wishes from Brazil Like Reply 2y Swatantra Dhara Swatantra Dhara This book is my Bible!!! <3 Like Reply 2y Renato Galindo Caceres Renato Galindo Caceres I am waiting for the release of the book translated into Spanish to buy it 📚 Like Reply 1 Like 2y Nicholas Graham Platt Nicholas Graham Platt Comes out in March Like Reply 1 Like 2y Jules Opperman Social Media and Business Management Jules Opperman Social Media and Business Management Just started reading. Have you researched redox signalling and ageing? Like Reply 1 Like 3y Doug Hart Doug Hart One of he most fascinating books I've ever read, very hard to put down. I suggest reading this to anyone that wishes to remain healthy and glimpse the future, because we appear to be due for some groundbreaking medical breakthroughs in the coming years! Like Reply 3 Likes 3y Joel Rönnberg Joel Rönnberg Halfway through the book now - and had about a dozen chills of anticipation about what the future has in store for us! One of the best books i've read, with gripping narrative, and the science, although challenging to grasp, very nicely put with helpful pictures along the way :) Thanks for the book David! Highly recommended! Like Reply 3y Denis Podrug, MBA, PMP Denis Podrug, MBA, PMP This book blew me away. I read hundreds in my life time and this one is certainly my top 5. Life changing material. Read it over one weekend as I couldn’t stop reading. Planning on reading it again. Like Reply 1 Like 3y See more comments To view or add a comment, sign inTo view or add a comment, sign in People David A. Dismiss Sinclair Ph.D., A.O. Dismiss Join now Sign in Two of my family's dogs. They ate the birthday muffins. And our pets will lead the way... David A. Sinclair Ph.D., A.O.Click here to view David A. Sinclair Ph.D., A.O.’s profile David A. Sinclair Ph.D., A.O. Professor at Harvard Medical School and Co-Host of the Lifespan Podcast Published Jul 24, 2018 + Follow Recently I got a letter from a man named Geoff, who wanted to know if I could help him extend the life of his daughter’s pet hamster. OK. I know that sounds funny. That’s fine. Allow yourself a chuckle—but then let’s think seriously about this. First, who wouldn’t want their animal companions to be around for longer? In my home, as in many homes, our dogs aren’t just pets; they’re truly part of our family. Others feel that way about their cats or their birds. And Geoff’s daughter apparently feels that way about her hamster, whose name is Hershey. Biologically speaking, a hamster isn’t radically different than a mouse. and we have overwhelming evidence of the effects of calorie restriction, longevity drugs and other interventions on mice. There are some vital caveats, of course, one of which is that, as researchers from Finland’s University of Kuopio found more than 20 years ago, the modes and expression of certain enzymes make hamsters different from both mice and humans with respect to the mechanism and metabolism of some drugs. So we probably can’t give a hamster the same dose of a drug like NMN as we give mice and expect the exact same results. But from yeast to roundworms to fruit flies to mice to monkeys, we’ve seen remarkable similarities in the ways in which organisms respond to treatments and therapies aimed at slowing, stopping and reversing aging, all of which would seem to point to a root evolutionary cause. And indeed, our pets may benefit from this research before we do. The process for FDA approval for pet treatments, after all, is a lot faster than it is for humans. And that means that dogs and cats (and yes, maybe hamsters) could be early beneficiaries of longevity therapies. In doing so, they’ll be helping pave the way for humans, too. How soon is all of this coming? Soon enough that it’s possible that little Hershey may indeed benefit. Hamsters live two to three years, on average. And Hershey is apparently a middle-aged rodent. But there’s a lot of research momentum in this arena, and a lot of interest on the part of consumers. In my experience, that’s a recipe for amazing things. Hi there. While you're here, jump on over to Twitter and say hello. I'm @davidasinclair. These articles are not intended to endorse any product or service. A ‘Fountain Of Youth’ Pill? Sure, If You’re A Mouse. The race for the cure to aging sparks hope and hype among top scientists — plus billions of dollars in investment. By Marisa Taylor FEBRUARY 11, 2019 A mouse in the pathology and geriatrics lab at the University of Michigan. (Melanie Maxwell for KHN) This story also ran on The Daily Beast. This story can be republished for free (details). Renowned Harvard University geneticist David Sinclair recently made a startling assertion: Scientific data shows he has knocked more than two decades off his biological age. What’s the 49-year-old’s secret? He says his daily regimen includes ingesting a molecule his own research found improved the health and lengthened the life span of mice. Sinclair now boasts online that he has the lung capacity, cholesterol and blood pressure of a “young adult” and the “heart rate of an athlete.” Despite his enthusiasm, published scientific research has not yet demonstrated the molecule works in humans as it does in mice. Sinclair, however, has a considerable financial stake in his claims being proven correct, and has lent his scientific prowess to commercializing possible life extension products such as molecules known as “NAD boosters.” His financial interests include being listed as an inventor on a patent licensed to Elysium Health, a supplement company that sells a NAD booster in pills for $60 a bottle. He’s also an investor in InsideTracker, the company that he says measured his age. Discerning hype from reality in the longevity field has become tougher than ever as reputable scientists such as Sinclair and pre-eminent institutions like Harvard align themselves with promising but unproven interventions — and at times promote and profit from them. Fueling the excitement, investors pour billions of dollars into the field even as many of the products already on the market face fewer regulations and therefore a lower threshold of proof. “If you say you’re a terrific scientist and you have a treatment for aging, it gets a lot of attention,” said Jeffrey Flier, a former Harvard Medical School dean who has been critical of the hype. “There is financial incentive and inducement to overpromise before all the research is in.” Mice frolic in Richard Miller’s pathology and geriatrics lab at the University of Michigan. Miller heads one of the three labs funded by NIH to test anti-aging substances on mice.(MELANIE MAXWELL FOR KHN) Elysium, co-founded in 2014 by a prominent MIT scientist to commercialize the molecule nicotinamide riboside, a type of NAD booster, highlights its “exclusive” licensing agreement with Harvard and the Mayo Clinic and Sinclair’s role as an inventor. According to the company’s press release, the agreement is aimed at supplements that slow “aging and age-related diseases.” Further adding scientific gravitas to its brand, the website lists eight Nobel laureates and 19 other prominent scientists who sit on its scientific advisory board. The company also advertises research partnerships with Harvard and U.K. universities Cambridge and Oxford. Some scientists and institutions have grown uneasy with such ties. Cambridge’s Milner Therapeutics Institute announced in 2017 it would receive funding from Elysium, cementing a research “partnership.” But after hearing complaints from faculty that the institute was associating itself with an unproven supplement, it quietly decided not to renew the funding or the company’s membership to its “innovation” board. “The sale of nutritional supplements of unproven clinical benefit is commonplace,” said Stephen O’Rahilly, the director of Cambridge’s Metabolic Research Laboratories who applauded his university for reassessing the arrangement. “What is unusual in this case is the extent to which institutions and individuals from the highest levels of the academy have been co-opted to provide scientific credibility for a product whose benefits to human health are unproven.” The bottom line is I don’t try any of these things. Why don’t I? Because I’m not a mouse. FELIPE SIERRA, THE DIRECTOR OF THE DIVISION OF AGING BIOLOGY AT THE NATIONAL INSTITUTE ON AGING AT NIH The Promise A generation ago, scientists often ignored or debunked claims of a “fountain of youth” pill. “Until about the early 1990s, it was kind of laughable that you could develop a pill that would slow aging,” said Richard Miller, a biogerontologist at the University of Michigan who heads one of three labs funded by the National Institutes of Health to test such promising substances on mice. “It was sort of a science fiction trope. Recent research has shown that pessimism is wrong.” Mice given molecules such as rapamycin live as much as 20 percent longer. Other substances such as 17 alpha estradiol and the diabetes drug Acarbose have been shown to be just as effective — in mouse studies. Not only do mice live longer, but, depending on the substance, they avoid cancers, heart ailments and cognitive problems. “Until about the early 1990s, it was kind of laughable that you could develop a pill that would slow aging,” says University of Michigan biogerontologist Richard Miller. “It was sort of a science fiction trope. Recent research has shown that pessimism is wrong.”(MELANIE MAXWELL FOR KHN) But human metabolism is different from that of rodents. And our existence is unlike a mouse’s life in a cage. What is theoretically possible in the future remains unproven in humans and not ready for sale, experts say. History is replete with examples of cures that worked on mice but not in people. Multiple drugs, for instance, have been effective at targeting an Alzheimer’s-like disease in mice yet have failed in humans. “None of this is ready for prime time. The bottom line is I don’t try any of these things,” said Felipe Sierra, the director of the division of aging biology at the National Institute on Aging at NIH. “Why don’t I? Because I’m not a mouse.” The Hype Concerns about whether animal research could translate into human therapy have not stopped scientists from racing into the market, launching startups or lining up investors. Some true believers, including researchers and investors, are taking the substances themselves while promoting them as the next big thing in aging. “While the buzz encourages investment in worthwhile research, scientists should avoid hyping specific [substances],” said S. Jay Olshansky, a professor who specializes in aging at the School of Public Health at the University of Illinois at Chicago. Yet some scientific findings are exaggerated to help commercialize them before clinical trials in humans demonstrate both safety and efficacy, he said. “It’s a great gig if you can convince people to send money and use it to pay exorbitant salaries and do it for 20 years and make claims for 10,” Olshansky said. “You’ve lived the high life and get investors by whipping up excitement and saying the benefits will come sooner than they really are.” EMAIL SIGN-UP Subscribe to KHN's free Morning Briefing. Your Email Address Your email address Promising findings in animal studies have stirred much of this enthusiasm. Research by Sinclair and others helped spark interest in resveratrol, an ingredient in red wine, for its potential anti-aging properties. In 2004, Sinclair co-founded a company, Sirtris, to test resveratrol’s potential benefits and declared in an interview with the journal Science it was “as close to a miraculous molecule as you can find.” GlaxoSmithKline bought the company in 2008 for $720 million. By the time Glaxo halted the research in 2010 because of underwhelming results with possible side effects, Sinclair had already received $8 million from the sale, according to Securities and Exchange Commission documents. He also had earned $297,000 a year in consulting fees from the company, according to The Wall Street Journal. At the height of the buzz, Sinclair accepted a paid position with Shaklee, which sold a product made out of resveratrol. But he resigned after The Wall Street Journal highlighted positive comments he made about the product that the company had posted online. He said he never gave Shaklee permission to use his statements for marketing. Harvard University geneticist David Sinclair poses for a portrait in the lab at Harvard Medical School in Boston last year.(CRAIG F. WALKER/THE BOSTON GLOBE VIA GETTY IMAGES) Sinclair practices what he preaches — or promotes. On his LinkedIn bio and in media interviews, he describes how he now regularly takes resveratrol; the diabetes drug metformin, which holds promise in slowing aging; and nicotinamide mononucleotide, a substance known as NMN that his own research showed rejuvenated mice. Of that study, he said in a video produced by Harvard that it “sets the stage for new medicines that will be able to restore blood flow in organs that have lost it, either through a heart attack, a stroke or even in patients with dementia.” In an interview with KHN, Sinclair said he’s not recommending that others take those substances. “I’m not claiming I’m actually younger. I’m just giving people the facts,” he said, adding that he’s sharing the test results from InsideTracker’s blood tests, which calculate biological age based on biomarkers in the blood. “They said I was 58, and then one or two blood tests later they said I was 31.4.” InsideTracker sells an online age-tracking package to consumers for up to about $600. The company’s website highlights Sinclair’s support for the company as a member of its scientific advisory board. It also touts a study that describes the benefits of such tracking, which Sinclair co-authored. Sinclair is involved either as a founder, an investor, an equity holder, a consultant or a board member with 28 companies, according to a list of his financial interests. At least 18 are involved in anti-aging in some way, including studying or commercializing NAD boosters. The interests range from longevity research startups aimed at humans and even pets to developing a product for a French skin care company to advising a longevity investment fund. He’s also an inventor named in the patent licensed by Harvard and the Mayo Clinic to Elysium, and one of his companies, MetroBiotech, has filed a patent related to nicotinamide mononucleotide, which he says he takes himself. Sinclair and Harvard declined to release details on how much money he — or the university — is generating from these disclosed outside financial interests. Sinclair estimated in a 2017 interview with Australia’s Financial Review that he raises $3 million a year to fund his Harvard lab. Liberty Biosecurity, a company he co-founded, estimated in Sinclair’s online bio that he has been involved in ventures that “have attracted more than a billion dollars in investment.” When KHN asked him to detail the characterization, he said it was inaccurate, without elaborating, and the comments later disappeared from the website. Sinclair cited confidentiality agreements for not disclosing his earnings, but he added that “most of this income has been reinvested into companies developing breakthrough medicines, used to help my lab, or donated to nonprofits.” He said he did not know how much he stood to make off the Elysium patent, saying Harvard negotiated the agreement. Harvard declined to release Sinclair’s conflict-of-interest statements, which university policy requires faculty at the medical school to file in order to “protect against any faculty bias that could heighten the risk of harm to human research participants or recipients of products resulting from such research.” “We can only be proud of our collaborations if we can represent confidently that such relationships enhance, and do not detract from, the appropriateness and reliability of our work,” the policy states. Elysium advertises both Harvard’s and Sinclair’s ties to its company. It was co-founded by Massachusetts Institute of Technology professor Leonard Guarente, Sinclair’s former research adviser and an investor in Sinclair’s Sirtris. Echoing his earlier statements on resveratrol, Sinclair is quoted on Elysium’s website as describing NAD boosters as “one of the most important molecules for life.” Supplement Loophole? The Food and Drug Administration doesn’t categorize aging as a disease, which means potential medicines aimed at longevity generally can’t undergo traditional clinical trials aimed at testing their effects on human aging. In addition, the FDA does not require supplements to undergo the same safety or efficacy testing as pharmaceuticals. The banner headline on Elysium’s website said that “clinical trial results prove safety and efficacy” of its supplement, Basis, which contains the molecule nicotinamide riboside and pterostilbene. But the company’s research did not demonstrate the supplement was effective at anti-aging in humans, as it may be in mice. It simply showed the pill increased the levels of the substance in blood cells. “Elysium is selling pills to people online with the assertion that the pills are ‘clinically proven’” said O’Rahilly. “Thus far, however the benefits and risks of this change in chemistry in humans is unknown.” “Many interventions that seem sensible on the basis of research in animals turn out to have unexpected effects in man,” he added, citing a large clinical trial of beta carotene that showed it increased rather than decreased the risk of lung cancer in smokers. Elysium’s own research documented a “small but significant increase in cholesterol,” but added more studies were needed to determine whether the changes were “real or due to chance.” One independent study has suggested that a component of NAD may influence the growth of some cancers, but researchers involved in the study warned it was too early to know. Guarente, Elysium’s co-founder and chief scientist, told KHN he isn’t worried about any side effects from Basis, and he emphasized that his company is dedicated to conducting solid research. He said his company monitors customers’ safety reports and advises customers with health issues to consult with their doctors before using it. If a substance meets the FDA’s definition of a supplement and is advertised that way, then the agency can’t take action unless it proves a danger, said Alta Charo, a former bioethics policy adviser to the Obama administration. Pharmaceuticals must demonstrate safety and efficacy before being marketed. “A lot of what goes on here is really, really careful phrasing for what you say the thing is for,” said Charo, a law professor at the University of Wisconsin. “If they’re marketing it as a cure for a disease, then they get in trouble with the FDA. If they’re marketing it as a rejuvenator, then the FDA is hamstrung until a danger to the public is proven.” “This is a recipe for some really unfortunate problems down the road,” Charo added. “We may be lucky and it may turn out that a lot of this stuff turns out to be benignly useless. But for all we know, it’ll be dangerous.” The debate about the risks and benefits of substances that have yet to be proven to work in humans has triggered a debate over whether research institutions are scrutinizing the financial interests and involvement of their faculty — or the institution itself — closely enough. It remains to be seen whether Cambridge’s decision not to renew its partnership will prompt others to rethink such ties. Flier, the former dean of Harvard Medical School, had earlier heard complaints and looked into the relationships between scientists and Elysium after he stepped down as dean. He said he discovered that many of the board members who allowed their names and pictures to be posted on the company website knew little about the scientific basis for use of the company’s supplement. Flier recalls that one scientist had no real role in advising the company and never attended a company meeting. Even so, Elysium was paying him for his role on the board, Flier said. Caroline Perry, director of communications for Harvard’s Office of Technology Development, said agreements such as Harvard’s acceptance of research funds from Elysium comply with university policies and “protect the traditional academic independence of the researchers.” Harvard “enters into research agreements with corporate partners who express a commitment to advancing science by supporting research led by Harvard faculty,” Perry added. Like Harvard, the Mayo Clinic refused to release details on how much money it would make off the Elysium licensing agreement. Mayo and Harvard engaged in “substantial diligence and extended negotiations” before entering into the agreement, said a Mayo spokeswoman. “The company provided convincing proof that they are committed to developing products supported by scientific evidence,” said the spokeswoman, Duska Anastasijevic. Guarente of Elysium refused to say how much he or Elysium was earning off the sale of the supplement Basis. MIT would not release his conflict-of-interest statements. Private investment funds, meanwhile, continue to pour into longevity research despite questions about whether the substances work in people. One key Elysium investor is the Morningside Group, a private equity firm run by Harvard’s top donor, Gerald Chan, who also gave $350 million to the Harvard School of Public Health. Billionaire and WeWork co-founder Adam Neumann has invested in Sinclair’s Life Biosciences. An investment firm led by engineer and physician Peter Diamandis gave a group of Harvard researchers $5.5 million for their startup company after their research was publicly challenged by several other scientists. In its announcement of the seed money, the company, Elevian, said its goal was to develop “new medicines” that increase the activity levels of the hormone GDF11 “to potentially prevent and treat age-related diseases.” It described research by its founders, which include Harvard’s Amy Wagers and Richard Lee, as demonstrating that “replenishing a single circulating factor, GDF11, in old animals mirrors the effects of young blood, repairing the heart, brain, muscle and other tissues.” Other respected labs in the field have either failed to replicate or contradict key elements of their observations. Elevian’s CEO, Mark Allen, said the early scientific data on GDF11 is encouraging, but “drug discovery and development is a time-intensive, risky, regulated process requiring many years of research, preclinical [animal] studies, and human clinical trials to successfully bring new drugs to market.” Flier worries research in the longevity field could be compromised, although he recognizes the importance and promise of the science. He said he’s concerned that alliances between billionaires and scientists could lead to less skepticism. “A susceptible billionaire meets a very good salesman scientist who looks him deeply in the eyes and says, ‘There’s no reason why we can’t have a therapy that will let you live 400 or 600 years,’” Flier said. “The billionaire will look back and see someone who is at MIT or Harvard and say, ‘Show me what you can do.’” Despite concerns about the hype, scientists are hopeful of finding a way forward by relying on hard evidence. The consensus: A pill is on the horizon. It’s just a matter of time — and solid research. “If you want to make money, hiring a sales rep to push something that hasn’t been tested is a really great strategy,” said Miller, who is testing substances on mice. “If instead you want to find drugs that work in people, you take a very different approach. It doesn’t involve sales pitches. It involves the long, laborious, slogging process of actually doing research.” KHN senior correspondent Jay Hancock contributed to this report. Marisa Taylor: mtaylor@kff.org, @marisaataylor This is not an advice article David A. Sinclair Ph.D., A.O.Click here to view David A. Sinclair Ph.D., A.O.’s profile David A. Sinclair Ph.D., A.O. Professor at Harvard Medical School and Co-Host of the Lifespan Podcast Published Jun 25, 2018 + Follow “Hi David. Thanks for everything you’re doing to increase healthy human lifespans. I’m excited by your research. Could you tell me what I should be taking?” “Dr. Sinclair, what supplement should I be taking?” “Dear David, I am not going to get any younger on my own. Would you please tell me how much NMN, NR, metformin or resveratrol I should be taking?” I get messages like this every day, and often multiple times each day. And even though I’d like to, I simply don’t have the time to respond to all of them. Hence this short article. First, though, a caveat. A big one. I DON’T GIVE ADVICE. Not on what chemicals you should put in your body, at least. If you’d like to know what restaurants to eat at in Boston, New York or Sydney, I might be your guy. But when it comes to how to live a longer and healthier life, I’m not going to tell you “do this” or “don’t do that.” I’m a researcher, not a medical doctor; I don’t make health and wellness recommendations. I don’t mind sharing what I do, though, for whatever that is worth. In fact, in the spirit of transparency, I think it’s rather important. I try to do everything I can to make my life and my work an open book. So, with all that in mind, strap in, because there’s a lot of stuff to go over. OK, I’m just kidding. It’s actually quite simple: • I take 750 mg of NMN every morning, along with a gram of resveratrol and 500 mg of metformin. Yup, that’s it. There are other things that I am doing with an eye toward making it to 100, very healthy and happy, and continuing onward from there — maybe I’ll write about those things here in the future if there’s interest — but when it comes to the longevity molecules I’m putting in my body, that really is it. And? So far so good. My resting heart rate is 57 — I checked it again this morning. That, I'm told, is the heart rate of an athlete, and I'm no athlete. My lungs operate at levels doctors expect to see among adults in their 20s — quite a shock since I’ve inherited the genetic lung defect that contributed to my mother’s death. My LDL cholesterol and blood pressure are both considered very healthy for a young adult. When I exercise with weights, I recover quickly — just like I did when I was in my 20s. When I run I get bored long before I get tired. What else would you like to know about my research and the fight against aging? Head on over to Twitter — you can follow me at @davidasinclair — and ask me a question. 298 66 Comments Like Comment Share Sophia Han Sophia Han This is Sophia ,i just check your article，NMN is effect for us .It is popupalr in market at present.and we can provide it Like Reply 2y Richard Robinson Richard Robinson Thank you very much for publishing this account of what you take re: anti-aging. Could you let us know your suppliers, or reliable suppliers, although i cannot get metformin as i live in the UK and it needs a GP prescription. I am thinking of taking NR as well. Also if somehow you publicised this article maybe you would get less requests for information. Like Reply 3y Jurgen Van Puyenbroeck Jurgen Van Puyenbroeck Hi, has anyone of you experience with the quality of NMN made in China? Like Reply 2 Likes 3y john pourchot john pourchot Dr. Sinclair, I really appreciate your research. I started taking NMN and NAD+ a couple of weeks ago. Based on the recommendation on the site where I purchased it, I have been breaking up the daily dosage of about 1G into smaller amounts, sublingual. Do you have any opinion on the value of sublingual vs. oral in terms of NMN? Like Reply 1 Like 3y Joseph Quispe Joseph Quispe Where do you get a gram of resveratrol a day? 500 mgs of pure resveratrol is like 300 bucks! Like Reply 3y Shawn Rogers Shawn Rogers I see 10g of Resveratrol Powder online for under $20. Claims to be 98% pure. How is that different from what you are seeing for at .5g for $300? Like Reply 1 Like 3y Robin Greenfr Robin Greenfr Hi and thanks for sharing:) What would you think about taking those anti aging molecule not every other day , but intermittently ,every 3days for example? Like Reply 4y Ali Khankan ,PMP,ITIL EXPERT Ali Khankan ,PMP,ITIL EXPERT i noticed that you feed your mice NMN in their drinking water, do you personally take NMN orally or sublingual? i understand from your research that NMN is more soluble than resveratrol? Like Reply 1 Like 4y Srinivas Sirigina Srinivas Sirigina Dr. Sinclair, Thank you for the podcast with Dr. Attia. It is very informative and thoroughly enjoyed it. Regarding the supplements you take, do you mind sharing the brands that you take. Like Reply 2 Likes 4y Alex Olteanu Alex Olteanu Any luck with finding what would be a decent brand for these supplements? Like Reply 4y Jose Ramos Jose Ramos Did you found out the brands or where to get it? Like Reply 4y Dennis Meyers Dennis Meyers Thanks for your podcast with Dr Attia. It was super informative. You mentioned in your podcast with Dr Attia that you take your resveratrol with fat. What source of fat do you take with it and how much? Like Reply 4y David A. Sinclair Ph.D., A.O. David A. Sinclair Ph.D., A.O. 1 gram of resveratrol mixes in nicely and cant taste it. Like Reply 1 Like 4y David A. Sinclair Ph.D., A.O. David A. Sinclair Ph.D., A.O. I make my own yogurt from http://bravoprobioticyogurt.com/ cultures and whole milk (which you can get on line) that is supposed to boost your immune system. Figured that messing with my microbiome might have fun effects. It's better than any store yogurt. Add fruit and stevia and All Bran. Have lost weight and not had a sniffle in 12 months since I started eating it. Like Reply 3 Likes 4y Beth Payne Beth Payne Thank you Dr Sinclair for all your work. I am very interested in the other factors you refer to in this article. My husband and I are taking NMN and would like to learn about what else you consider to be essential to contribute to your longevity. Could you please share the other things you do to live longer. Thanks. Like Reply 4y David A. Sinclair Ph.D., A.O. David A. Sinclair Ph.D., A.O. Thanks Beth. Well I'm only 49 so I don't have longevity...yet. 1. Eat less. Be hungry once a day. 2. Eat leafy vegetables. 3. Avoid eating mammals, bread, sugar. 4. Use the stairs. 5. Run once a week at least. 6. Don't bundle up at night. You'll burn more energy. Like Reply 4 Likes NOVOS The Anti-Aging Supplements David Sinclair Takes 07.11.2022 novos Try NOVOS Today RECOMMENDED NOVOS Core Starting at $79/mo View Product David Sinclair is a professor at Harvard University who has been studying aging for the better part of his academic career. Dr. David Sinclair’s main research interest is the epigenetics of aging, with a focus on epigenetic reprogramming of aging (e.g. reversing aging via Yamanaka factors), NAD+ metabolism and sirtuins, and NAD+ precursors like NR and NMN. You may have come across his published, New York Times best-selling book on aging, “Lifespan: Why We Age – And Why We Don’t Have To”, going deeper into those subjects (you can find our favorite longevity books here). So what supplements does Professor David Sinclair take to live longer? Keep in mind that to date, Dr. David Sinclair has made a point to not promote or endorse any supplement products. We compiled this list from interviews and books in which Professor David Sinclair mentions supplements he takes. We don’t know if he still takes these supplements, or whether he takes additional supplements that are not included on this list. For example, in his book Lifespan, he mentions on page 304 that he takes NMN and resveratrol every morning, often mixed in his yogurt. Based on multiple, recent interviews and his book, Dr. David Sinclair’s supplement and longevity drug stack likely looks as follows: 1. Nicotinamide mononucleotide (NMN): 1g per day, in the morning 2. Resveratrol: 1g per day, in the morning 3. Metformin: 800 mg, in the evening 4. Vitamin D3: ideally 4000 to 5000 IU per day 5. Vitamin K2: ideally 180 to 360 microgram per day 6. Statin 7. Low-dose aspirin: 83 mg per day 8. Alpha lipoic acid (ALA): recent status unknown 9. Coenzyme Q10 (coQ10): recent status unknown 10. Spermidine: 1 mg per day, in the morning 11. Quercetin and fisetin: 500 mg each, once per day, in the morning 12. TMG (trimethylglycine or betaine): 500 mg to 1000 mg per day 1. Nicotinamide mononucleotide (NMN), 1g per day, in the morning Our view: We are enthusiastic about NMN. NMN has been shown to slow down many aspects of aging in animal studies (R,R,R,R). NMN is a precursor to NAD+, an important metabolic molecule that many proteins need to properly carry out their function, like protecting and repairing our DNA and epigenome. 1000 mg is a high dose of NMN. 250 to 500 mg is also sufficient to benefit from NMN’s health and longevity promoting effects. In fact, studies done in humans with NMN use 250 mg per day (R,R). It’s interesting to know that David Sinclair takes NMN and not NR (another much touted “longevity” supplement). Despite all the hype on the internet, NR does not extend lifespan (R). Professor Sinclair considers NMN to be superior to NR. Learn more about the differences between NMN and NR here. 2. Resveratrol, 1g per day, in the morning Our view: We are lukewarm about resveratrol. We believe pterostilbene is better. Resveratrol is a stilbenoid found in the skin of grapes in low amounts. Studies have shown that resveratrol can reduce the risk of heart disease, cancer and neurodegeneration. David Sinclair believes that resveratrol works synergistically with NMN. Resveratrol is needed to activate the sirtuin genes (which protect our DNA and epigenome), while NMN is needed to fuel the sirtuins. However, resveratrol is difficult to be absorbed by the gut, and the little resveratrol that ends up in the body is broken down very quickly. Therefore, pterostilbene is a better alternative. Pterostilbene is a molecule that looks very similar to resveratrol, but it is absorbed considerably better and is far more stable in the human body. Various studies show that pterostilbene works better than resveratrol regarding anticancer, antidiabetic and cardioprotective effects (R,R,R). 3. Metformin (prescription drug): 800 mg, in the evening Our view: We are cautiously optimistic about metformin, keeping in mind some caveats. Metformin has shown to extend lifespan in various organisms, including mammals (R,R). In humans, we see that diabetics taking metformin actually live longer than healthy non-diabetics who obviously don’t take metformin (R). This was not the case for diabetics on other anti-diabetic drugs. Taking metformin can, however, have side effects. In the short-term, metformin can cause diarrhea and gastrointestinal discomfort, which often subsides after a few weeks. In the long-term, metformin can reduce the uptake of vitamin B12. Metformin probably works as a hormetic substance, meaning that it causes a little bit of damage to our cells so that our cells are put in a repair and protect modus. Metformin inhibits mitochondrial function, so the mitochondria will repair and protect themselves better. Therefore, given exercise also “damages” the mitochondria somewhat (so that afterwards they will repair themselves, which is one of the health benefits of exercise) he does not combine metformin with exercise given that could put too much stress on the mitochondria. That is why Prof Sinclair does not take metformin on the days he exercises. Also, recent studies suggest that perhaps very old people should not take metformin, given metformin causes too much stress on already very old and very stressed mitochondria (R). We wrote an article about natural alternatives for metformin here. Furthermore, David Sinclair takes metformin in the evening, before going to bed. He says this because during the night, the body is already in a fasting state and metformin could further advance this state. However, we would recommend taking metformin always before the largest meal (ideally 20 minutes before mealtime). This way, metformin can make the body more insulin sensitive when it matters the most: during and in the hours after a meal, when mitochondria have to process the sugars and fats from the meal. This is also how metformin is ideally prescribed according to medical guidelines. Furthermore, during the night, you are already in a fasting (insulin sensitive) state. It could be better to get the body more into an insulin sensitive state during the day too, especially when processing carbohydrates and fats after a meal. David Sinclair takes 800 mg of metformin only once per day. We would prefer lower doses spread over the day, like 500 mg twice daily, before lunch (500 mg) and before dinner (500 mg) – not in the morning because this is when the body is already most insulin sensitive anyhow. 4. Vitamin D3 Our view: We are positive about this vitamin. Vitamin D can extend lifespan, at least in simple organisms (R). Vitamin D can reduce the risk of various aging-related diseases. Vitamin D deficiency in humans has been associated with an increased risk of heart disease, type 2 diabetes, autoimmune diseases and Alzheimer’s disease. Vitamin D activates many genes that confer important health benefits (R). The dose of vitamin D that most governments advise is too low (e.g. 400 to 800 IU per day). Most vitamin D experts advise to take at least 4000 to 5000 IU per day, and get your vitamin D levels checked at least every year. Vitamin D is one of our supplements everyone should take for optimal health. 5. Vitamin K2 Our view: We like vitamin K (a lot). Vitamin K is important not just for bone health, but also vascular and mitochondrial health. Vitamin K also improves skin appearance. If you take vitamin D, you ideally also combine it with vitamin K2 (MK-7 is the best form): the two vitamins work synergistically. Ideally, doses of vitamin K2 are 180 to 360 microgram per day. However, taking only a few vitamins, like vitamin K and vitamin D, is not going to cut it: most people are deficient in many other vitamins, minerals and micronutrients, even when they eat healthy. Learn more about the vitamins, minerals and other nutrients everyone should take here. 6. Statin (prescription drug) – taken since his early 20s due to family history of cardiovascular disease Our view: We are not big fans. Statins could lower the risk of heart disease. But there is a lot of discussion about how significant the effect of a statin is on reducing the cardiovascular risk. Some scientists claim you should take statins if you have an increased risk of getting a heart attack (known as “primary prevention”), while others claim that you should only take statins when you’ve already had a heart attack (as “secondary prevention”). Other studies suggest that for many people, statins don’t work very well for primary prevention. This will likely depend on your personal genetic make-up; we see that some people react much better to statins while others derive no effect (R). Also, not all statins are the same. Some statins seem to be able to extend lifespan in mice (like simvastatin) while other statins do not have this effect. Also, statins can have side effects, like muscle aches or neuropathy (nerve pain), and some statins more than others. After all, statins inhibit the production of cholesterol, a molecule that is an important component of our cell membranes, especially of neurons and muscle cells. 7. Low-dose aspirin – 83 mg per day Our view: Neutral, but also a bit disappointed. A low dose aspirin could reduce inflammation, reduce the risk of heart attacks, and perhaps the risk of cancer. However, a recent large study that involved almost 20,000 participants and that lasted 4.7 years showed that a low dose of aspirin did not reduce cardiovascular disease and did not improve survival (R). In fact, it even showed that it could actually increase cancer risk somewhat (R), despite many other studies showing that aspirin could have health and longevity benefits. Further studies have to be conducted to sort this out. 8. Alpha lipoic acid (ALA) Our view: This antioxidant very likely does not extend lifespan in humans. In fact, it may actually even shorten lifespan. Note: According to earlier sources, Dr. Sinclair mentioned taking alpha-lipoic acid. However, in recent interviews (done in 2022) David Sinclair didn’t specifically mention taking this supplement. Alpha lipoic acid (ALA) is a strong antioxidant. There has been a bit of a hype around ALA, especially combined with acetyl-L-carnitine (ALCAR), to slow down aging. However, there are various studies showing that ALA does not extend lifespan or slow down aging (R). However, alpha lipoic acid is a strong antioxidant, and scientists have learned that antioxidants could actually accelerate aging (as we explain here). So we should not be surprised to see that in studies in which aging mice receive alpha lipoic acid their lifespans are actually shortened (R,R). This why alpha lipoic acid is one of the anti-aging supplements you should not take. In short, we would be careful with taking supraphysiological doses (much greater than you’d ever find in a healthy diet) of antioxidants. 9. Coenzyme Q10 (coQ10) Our view: This antioxidant probably cannot extend lifespan in humans. It could possibly even shorten lifespan. Note: According to earlier sources, Dr. Sinclair mentioned taking coenzyme Q10. However, in recent interviews (done in 2022) David Sinclair didn’t specifically mention taking this supplement. Coenzyme Q10 is an antioxidant that improves mitochondrial functioning. There is insufficient scientific evidence (at least in well-conducted studies with the right disease model mice) that coenzyme Q10 can extend lifespan. Various studies show that coenzyme Q10 does not extend lifespan (R,R,R,R). Some studies show that coenzyme Q10 can actually shorten lifespan (R). Also, coenzyme Q10 is an antioxidant. In recent years, scientists have learned that antioxidants can actually accelerate aging (for reasons described here). We would be cautious about taking strong antioxidants like coenzyme Q10 to extend lifespan. That is also why we added coenzyme Q10 to the list of anti-aging supplements one should not take for longevity. 10. Spermidine, 1 mg per day, in the morning Our view: We think spermidine is an interesting molecule for longevity. Spermidine is a molecule first found in sperm, hence its name. As a supplement, spermidine is extracted from wheat-germ. It can also be found in foods like cheese, soy, legumes, and mushrooms. Spermidine can impact important aging-mechanisms, such as autophagy. Studies have shown that spermidine can improve various biomarkers of health and longevity (R), and that spermidine can extend lifespan in different organisms, including mice (R). We wrote more about spermidine and longevity here. 11. Quercetin and fisetin, 500 mg each, once per day, in the morning Our view: we like fisetin more than quercetin. We would also reduce the dose. Quercetin and fisetin are very similar molecules. They are often called “senolytics”, in the sense they are assumed they can clear away senescent cells. Senescent cells are cells that accumulate during aging and secrete substances which damage normal healthy cells (learn more here). However, we believe the main reason why molecules like fisetin can extend lifespan is because of other effects than being a “senolytic”, such as by reducing inflammation. For this reason, we prefer fisetin taken in lower doses (100 mg per day) and in a continuous way, instead of in higher doses (e.g. 1000 mg or more) once every month in order to “clear” senescent cells. We prefer fisetin more than quercetin. One reason is that there are more and better studies done with fisetin showing longevity effects, such as studies in mice demonstrating that fisetin extends lifespan (R). Learn more about fisetin and longevity here. 12. TMG (trimethylglycine or betaine) Our view: combining TMG with NMN makes sense, but we prefer phosphatidylcholine (or a combination of TMG with phosphatidylcholine). Dr. David Sinclair mentioned in podcasts that he takes TMG (trimethylglycine) to err on the safe side regarding the possibility of NMN reducing methylation in the body. Methyl groups are small molecules that are put on DNA, proteins and substances in order for them to work properly. For example, methylated DNA (DNA covered with methyl molecules) prevents that DNA from being active (learn more about the epigenome here). Methyl molecules are also sometimes linked to specific substances in order for them to be broken down. NMN is used by cells to create NAD+, a molecule pivotal for health. However, when NAD+ is used by the body, nicotinamide is formed. This molecule needs to be disposed of. In order to do so, a methyl group is placed on nicotinamide so it can be secreted by the kidneys. So if people take a lot of NMN, lots of methyl groups could be used. TMG provides methyl groups (TMG consists of 3 methyl groups per TMG molecule). We agree with David Sinclair that adding TMG could be worthwhile. A proper dose would be, for example, 500 mg to 1 gram of TMG per day. However, some people experience gastro-intestinal issues from TMG, or have difficulty sleeping after taking it. Therefore, as alternatives, one can take phosphatidylcholine, which can also deliver methyl groups. It also improves brain health and cognition. One can also drink green tea when taking NMN. Green tea contains EGCG, which inhibits the enzyme that puts methyl groups on nicotinamide (the enzyme is called “NNMT”). This way, less methyl groups are used to methylate nicotinamide. We wrote more about methylation and NMN here. OTHER THINGS DAVID SINCLAIR DOES TO LIVE LONGER Of course, Dr. David Sinclair does not only rely on supplements to live longer and healthier. He knows very well that nutrition, exercise, proper sleep and stress reduction are also very important methods to extend lifespan. How does he go about this? 1. Nutrition David Sinclair often eats only 2 meals per day instead of 3 meals. He drinks lots of green tea and very little alcohol. He eats little (red) meat, and consumes lots of vegetables. Professor Sinclair is a proponent of regular fasting. We wrote more about Sinclair’s longevity regimen here. You can read more about the best longevity diet (and download the poster!) here. 2. Exercise Regarding exercise, David Sinclair runs once or twice a week, both in a low intensity and high-intensity way. He also does weight lifting once or twice a week. 3. Health tracking Professor Sinclair uses a continuous glucose monitor (CGM) to track how the foods he eats increase his blood sugar levels. Examples of continuous glucose monitors are FreeStyle Libre or Levels (not sponsored). He also does regular blood tests to track his health. We wrote about the best blood tests for longevity here. CONCLUSION We think that the list of supplements that David Sinclair is not bad, but can be further improved. In this regard, we make the distinction between longevity supplements and health supplements. Longevity supplements, like NMN, micro-dosed lithium or calcium alpha-ketoglutarate, could actually slow down aging. Health supplements enable our body to work properly: deficiencies of them could accelerate aging. Find here a list of the best longevity supplements, and find here an overview of health supplements that everyone should take. Learn more about the anti-aging supplement NOVOS Core