Australian IVF mix up ‘probably not the first time'

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

The Age

an hour ago

The Age

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

This story is part of the June 14 edition of Good Weekend. See all 14 stories. For a man approaching his 56th birthday, David Sinclair looks to be in excellent shape. Thick, dark hair. Gleaming white teeth. Skin so smooth it's almost spooky. As the celebrated scientist sips matcha green tea at an outdoor cafe on a sunny Sydney morning, I find myself surreptitiously studying his forehead. OK, there are a couple of faint lines, but nothing you could classify as a wrinkle. If he were a used car, you'd say he was in as-new condition. What's his secret? Sinclair's answer is basically that humans, like automobiles, benefit from assiduous maintenance. 'I've always regarded the body as something that you should really take care of,' he says. Caring for the body, specifically holding off the wear and tear associated with ageing, is in Sinclair's case both a personal and professional mission. Australian by birth, he has lived for the past 30 years in the US, where he is a professor of genetics at Harvard Medical School in Boston and a leader in a booming field of scientific endeavour that might be summed up as a quest for eternal youth. The aim is to slow the ageing process in our cells, enabling us to extend our lifespan and, in effect, stay younger for longer. Sinclair takes this a step further, arguing that ageing can be not only delayed, but reversed. Because that's an attractive notion to a lot of people, and because Sinclair makes it sound entirely plausible, his work has brought him money and fame. The Wall Street Journal, which calls him 'the longevity business's brightest star and chief salesman', estimates that investors have pumped more than $US1 billion into biotech enterprises he has spun out of ideas generated in his Harvard laboratory. He has an agent, a publicist, a bestselling book (Lifespan: Why We Age – and Why We Don't Have To), a podcast, more than 1.2 million followers on social media and a calendar filled with speaking engagements. He also has critics. A press release issued last year quoted Sinclair as saying that a company he co-founded, Animal Biosciences, had developed a canine nutritional supplement proven to reverse ageing in dogs. 'That is a lie,' American biologist Matt Kaeberlein responded on X, going on to describe Sinclair as 'the textbook definition of snake oil salesman'. Sinclair said he had been misquoted. Nevertheless, Kaeberlein and others resigned in protest from the Academy for Health & Lifespan Research, a nonprofit organisation co-founded by Sinclair. After a tense meeting of the academy's board, Sinclair relinquished the presidency. To me, he insists that he wasn't pushed out. 'I was going to step down anyway because it was quite a distraction from my research,' he says. 'I didn't have time for the in-fighting.' Sitting with us at the cafe table is Sinclair's partner of four years, Serena Poon. I don't have to ask how he feels about her: I've read his heartfelt tributes on Instagram ('Serena My Love, I feel like the luckiest guy on Earth, having found my perfect match'). Poon, 49, is from California, where she trained as a nutritionist and worked as a private chef – including a couple of years cooking for publisher Hugh Hefner at the fabled Playboy Mansion in Los Angeles. She now bills herself as a 'longevity wellness expert'. She has her own brand, Serena Loves, and sells products such as 'Aura Cleansing Mist with Pure Organic Bulgarian Rose Water' (from $US67 plus postage). Sinclair credits Poon with improving his eating habits: she has weaned him off dairy food and meat, as well as alcohol. It was Poon, too, who introduced him to drinking matcha, which is made from the powdered leaves of tea bushes deprived of sunlight for part of their growing period. The theory is that the resulting stress on the plants produces a brew rich in beneficial antioxidants. 'Every morning we have at least one of these,' Sinclair says, gesturing to the green drink in front of him. That's after he has taken his daily dose of three chemical compounds he believes slow ageing: resveratrol, nicotinamide mononucleotide (NMN) and the diabetes drug metformin. He also swallows vitamins D and K². In other measures aimed at increasing his chances of being around to meet his great-great-grandchildren (to whom he dedicated his book), he sleeps in a bed that lowers his body temperature during the night. He works at a standing desk. He rinses his mouth with coconut oil. He exercises. The dietary changes encouraged by Poon seem to Sinclair to have had visible results. 'You said my skin looks better?' he says, turning to her for confirmation. 'Yes,' she assures him. 'You look younger now than you did when we met.' Gift for overpromising In person, Sinclair is affable and softly spoken. In the spotlight, he morphs into a performer, with a showman's propensity to make sweeping claims ('the first person to live to 150 has already been born') and a habit of presenting himself in a heroic light ('my goal is to save millions of lives'). The flourishes that add colour to his TED Talks and media appearances do not necessarily endear him to fellow scientists. 'David is a gifted storyteller,' says leading biochemist Charles Brenner, based at the City of Hope National Cancer Centre in Los Angeles County. 'He uses rhetorical devices to try to convince people that there is evidence for things that aren't really true.' To some, the most compelling proof of Sinclair's persuasiveness was the decision by pharmaceutical giant GSK – then GlaxoSmithKline – to pay $US720 million for Sirtris Pharmaceuticals, a company he had founded to develop anti-ageing drugs based on resveratrol. Sinclair had only a minor shareholding by the time the purchase was made in 2008 but still collected about $US8 million. (He tells me he can't recall the exact sum.) Eyebrows were raised when GSK stopped resveratrol trials a few years later, having failed to get worthwhile results. 'He pulled off a massive sale of something that didn't work,' says American investigative journalist Scott Carney. Former Harvard Medical School dean Jeffrey Flier has accused Sinclair of failing to acknowledge holes found in his science. 'It's not a good practice to cite a 2006 paper of yours that has been seriously and multiply refuted since then,' Flier said on social media in 2022. When Sinclair responded by blocking communication with him, Flier told followers on X: 'I crossed the line by noticing a major piece of his research was untrue, and I expressed concern that he continued to tout it as true …' Sinclair is a scientific rock star. In 2014, the year he was awarded the Australian Society for Medical Research Medal, Time magazine named him one of the world's 100 most influential people. In 2018, he was appointed an Officer of the Order of Australia (which he tells readers of his book is 'the equivalent of a knighthood'). Earlier this year, at a forum in Berlin, the Cinema for Peace Foundation presented him with something called the Noble Genius Award. In March, he was an honoured guest at the World Science Festival in Brisbane. Researching this story, I start to wonder who and what to believe. Is longevity science the force for good it's cracked up to be, or should I listen to Ukrainian molecular cell biologist Leonid Schneider, publisher of the For Better Science blog, who says 'the whole anti-ageing business is a huge scam'? Is Sinclair a noble genius or, as Scott Carney alleges, 'just the most prominent and successful of the longevity grifters'? Does Sinclair owe his youthful appearance to clean living and anti-ageing supplements or – as online snarks suggest – to hair dye and Botox injections? These questions are playing on my mind as I browse through Sinclair's Instagram account a few days after our meeting in the cafe. In one post, he recommends drinking matcha: 'It helps burn fat when you walk, protects kidneys from damage, improves memory, decreases inflammation and kills cancer cells.' Jeepers. If I'd known that, I'd have had a cup myself. Research race Kicking on to a ripe old age is more common than at any time in human history. In Australia and other high-income countries, the average life expectancy at birth rose by about 30 years in the 20th century, thanks largely to medical advances, vaccination programs and other improvements in public health. But according to a report published last year in the journal Nature Aging, gains in longevity have slowed since 1990 and will probably continue to decelerate as life expectancy approaches a biological ceiling. The report said that, this century, at most 15 per cent of females and 5 per cent of males are likely to reach the age of 100. Unless, of course, scientists can figure out how to slow our bodies' natural rate of decline. We age because our cells gradually deteriorate, functioning less efficiently and losing the ability to repair and renew themselves. What isn't clear is why this happens, and what, if anything, can be done to stop it. In a recent book, Why We Die: The New Science of Ageing and the Quest for Immortality, Nobel Prize-winning molecular biologist Venki Ramakrishnan writes that more than 700 biotech companies with a combined market cap of at least $US30 billion are racing to solve the puzzle. Ramakrishnan notes that tech billionaires Peter Thiel, Elon Musk, Larry Page, Sergey Brin, Jeff Bezos and Mark Zuckerberg have all shown interest in the research. 'And in many cases, they are funding it.' Blogger Leonid Schneider finds something unseemly in the scale of the effort. 'There are a lot of very rich people who know they will die one day and it makes them very sad, because they will be separated from their money,' Schneider says. 'This is where the whole business starts.' Philanthropist Bill Gates has expressed a similar view, pointing out that, in parts of the world, children continue to die from preventable diseases: 'It seems pretty egocentric, while we still have malaria and TB, for rich people to fund things so they can live longer.' Sinclair has a different perspective. For him, he says, the quest is intensely personal. During his childhood on Sydney's upper north shore, he spent a lot of time with his beloved grandmother, Vera, who had fled to Australia after the failure of the 1956 uprising in her native Hungary. (Her only son, Sinclair's father Andrew, changed the family name from Szigeti.) Sinclair was just four when Vera broke the news to him that no one lived forever: she would die one day, as would his parents – both biochemists – and his younger brother. Even the pet cat would die. 'As a four-year-old, that really freaks you out,' Sinclair said on the popular podcast hosted by US comedian Joe Rogan. 'That was a turning point in my life.' Sinclair understood from an early age that Vera expected big things of him. 'She said, 'I'm going to pour love into this child, and make him the vehicle to change the world, to make it a better place.' ' Her message was explicit: 'My grandmother said, 'Do something important.' So I said, 'I'll try to stop people getting old and sick.' I remember the exact moment. I remember where I was, what we were doing, what the carpet felt like.' I end up watching YouTube videos of all three of Sinclair's appearances on Rogan's show. During the first, in 2019, the podcaster says to him: 'You don't have grey hair. That's weird, isn't it? You don't have any?' Later, he asks Sinclair what can be done to mitigate the effects of ageing on the skin. 'You mean besides Botox and stuff?' Sinclair says. Botox isn't an anti-ageing substance, Rogan replies. 'It just freezes your face, like a weirdo.' Rogan can't understand why people use it. Especially males. 'When I see a man whose forehead doesn't move, I want to smack him in the mouth,' he says. Sinclair seems keen to change the subject. 'I don't spend a lot of time thinking about the cosmetic industry,' he says. 'For obvious reasons. I'm trying to save humanity and improve the planet.' A real go-getter When Sinclair enrolled in a science course at the University of NSW in 1987, he was convinced that his would be the last generation whose lives would be limited to the standard length. 'I was obsessing over this, and it was depressing me,' he tells me, recalling an occasion in a campus cafe when he snapped. 'My friends were smoking and drinking beer and playing cards and I just said, 'Stop! Do you realise that we were born one generation too early?' They were like, 'Yeah, whatever, David. Get a drink.' ' At 25, freshly armed with a PhD in molecular genetics, Sinclair bought himself a ticket to Boston. He had landed a job studying ageing in yeast cells in a laboratory at the Massachusetts Institute of Technology. One of his colleagues was Brian Kennedy, now a longevity scientist at the National University of Singapore, who remembers him as a real go-getter – smart, hard-working and 'very aggressive about what he was doing in the lab'. Another colleague was Matt Kaeberlein, who would later call Sinclair a snake-oil salesman but had no complaints about him then. 'He was very supportive, very helpful, a fun guy to be around,' Kaeberlein says. Loading By the age of 30, Sinclair was an assistant professor at Harvard. At 34, he was described in a 2004 article in Science, the journal of the American Association for the Advancement of Science, as 'deeply ambitious, relentlessly competitive, supremely self-confident'. Two years later, Sinclair and his Harvard research team published a paper that said overweight laboratory mice aged more slowly and stayed healthier if fed resveratrol, a plant-derived enzyme found in red wine. Resveratrol activated a protein called a sirtuin, which is involved in metabolic regulation, the paper said, and the sirtuin increased the rodents' longevity. This seemed to tie in with the 'French paradox' – the fact that the citizens of France, who drink a lot of wine, have a relatively low incidence of coronary heart disease despite a diet high in saturated fats. The paper made a major splash. Resveratrol was hailed as a wonder drug and Sinclair was everywhere in the media. When GlaxoSmithKline paid crazy money for his Sirtris Pharmaceuticals in 2008, he appeared to have hit the jackpot, both scientifically and financially. But over the next few years, reputable researchers released studies that disputed Sinclair's claims. They said resveratrol did not, in fact, activate sirtuins: the anti-ageing effect that Sinclair had observed was due to the fluorescent dye used in his experiments. This got much less attention than the original story, but Sinclair was nonetheless hurt and indignant. He told Joe Rogan: 'There were days when I said, 'Screw humanity. I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives.' ' In fact, it wasn't the first time Sinclair's work had been challenged. His former colleagues, Brian Kennedy and Matt Kaeberlein, had tried unsuccessfully to replicate an earlier study in which Sinclair examined resveratrol's impact on ageing in yeast. 'We couldn't reproduce the ability of resveratrol to extend lifespan,' Kaeberlein tells me. After many failed attempts, the pair contacted Sinclair and asked for guidance: what were they doing wrong? 'Basically, we got the runaround,' says Kaeberlein. In 2004, he and Kennedy co-authored a paper that set out their findings: 'We didn't claim there was fabrication of data or anything,' Kaeberlein says. 'We just said, 'We can't reproduce the lifespan effect.' ' Sinclair still maintains he was right about resveratrol and says a study he published i n 2013 confirmed it. A substantial body of evidence contradicts that view. 'Nobody in the ageing field really is studying resveratrol any more,' says Kaeberlein. 'Everybody recognises this was a false lead.' Sinclair insists to me that the work of his laboratory has always been rigorous and accurate. 'None of our theories, none of our papers, have ever been proven wrong,' he says. Ageing action man Vera lived to the age of 92, but she had long been a shadow of her former self. Witnessing his grandmother's frailty in her final years strengthened Sinclair's resolve to save future generations from drawn-out decrepitude. Throwing himself into his research, he formulated a new theory, which is that ageing is caused by damage to the epigenome – the part of our cells that turns genes on or off. 'As we get older, we lose the ability to read our DNA correctly,' he says, and this ultimately causes cells to function abnormally. He argues that by using gene therapy to reprogram our cells, we can erase the corrupt signals that set them on the path to ageing. He gets a laugh at conferences when he says he no longer looks at a person as 'old': 'I just look at them as someone whose system needs to be rebooted.' Sinclair's mother, Diana, was diagnosed with lung cancer at the age of 50. A smoker, she had one lung removed and lived another 20 years, until 2014. In Lifespan, Sinclair writes that his father, Andrew, began to get a bit doddery in his mid-70s. Following Sinclair's example, Andrew started taking NMN, a molecule that converts in the body into nicotinamide adenine dinucleotide (NAD+), which helps build and maintain the structure of cells. Our levels of NAD+ decline with age, Sinclair says. He believes boosting the levels can make cells behave as if they are younger. The way Sinclair tells it in his book, the transformation in Andrew has been astonishing: these days, his father is a veritable action man – the kind of guy who hikes through wind and snow to the peak of Tasmania's highest mountain, goes whitewater rafting in Montana, explores ice caves in Austria. Sinclair told Joe Rogan in 2021 that Andrew had climbed 40 flights of stairs in 15 minutes. 'Holy shit,' Rogan replied. When Andrew visited Boston last year, Sinclair posted a picture on Instagram of the two of them posing with his son (he has three children with his ex-wife, molecular biologist Sandra Luikenhuis). 'Dad's over from Australia for his 85th birthday,' Sinclair wrote. 'He is a machine. No jet lag and fitter than Ben and me.' On meeting Andrew in Sydney, I ask for his own account of how the NMN has affected him. 'Probably gives you more energy,' he says mildly. A while later, in April, I see that Sinclair has posted a photograph of himself and Andrew at the top of the Sydney Harbour Bridge, which they had climbed. In his caption, Sinclair has again portrayed Andrew as freakishly hale and hearty: 'He doesn't even need glasses to drive at night!' Examining the picture, I register that in one respect at least, Andrew is a normal 85-year-old: the small amount of hair left on his head is silver-grey. The contrast with Sinclair's luxuriant dark locks is striking. Reputation for hyperbole On Sinclair's social media accounts, happy snaps of his family and laboratory staff are interspersed with startling scientific announcements. 'Age reversal works in primates to restore vision,' he tweeted in April 2023. '… Next up: age reversal in humans.' Three months later, he declared: 'This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating age-related diseases.' The post got the attention of the world's richest man, Elon Musk, who responded: 'OK, so what exactly is it?' Others, aware of Sinclair's reputation for hyperbole, urged caution. 'Many reasons to be concerned about these claims,' wrote Jeffrey Flier, the former Harvard dean. Matt Kaeberlein kept his comment short: 'Nobody has a drug to reverse aging.' Not yet, Sinclair concedes. But he is confident that, thanks to the cell-reprogramming gene therapy invented in his laboratory and developed by a company he chairs, Life Biosciences, such a drug is on the way. The therapy has been used to restore sight in monkeys, he tells me. 'Early next year we hope to treat the first blind human patient with this technology. If that works, I will be happy to say that, yes, we can rejuvenate parts of humans. And ultimately the whole body.' Think of the way a salamander regrows a limb, he says. If they can do it, why can't we? 'I believe we've uncovered that mechanism, which we've lost over time.' This idea turns anti-ageing science on its head, says Tristan Edwards, the Australian former hedge-fund manager who founded Life Biosciences with Sinclair in 2016. In the main, longevity researchers have concentrated on extending our productive lifespan by building our resistance to the ailments of old age, Edwards says. 'Now the focus is on having everyone just regenerate and be young and healthy indefinitely. If everyone is essentially 25 for a thousand years, you don't need to worry about Alzheimer's any more. Cardiovascular disease isn't a thing.' Life Biosciences chief executive Jerry McLaughlin, who has travelled extensively with Sinclair, reports that he is recognised all over the world. Not long ago they were having a snack in a Marriott hotel in Saudi Arabia when they realised that the two other people in the lounge were staring at the scientist. 'I feel for him sometimes,' McLaughlin says. 'It's part of the price you pay for doing such wonderful work.' Bogus claims He isn't in it for the money. Sinclair would like to make that clear. 'People think I'm a multimillionaire, living the high life,' he says. What they don't realise is that he has ploughed almost everything he has earned back into his work: 'I would rather fund medical research and clinical trials than own a house.' He does have a weekender at Cape Cod, but it's mortgaged, he says. He rents his apartment in Boston. 'I don't want to die rich. I don't even want my kids to die rich. I want to fulfil the mission.' US President Donald Trump has threatened a $US3 billion ($4.6 billion) cut in federal funding to Harvard, the oldest and wealthiest university in the country. Sinclair expects his lab to lose grants worth about $US2 million, which will mean halting some research projects. 'It's a tragedy,' he says. 'It's forcing me to focus on generating revenue that I can funnel into research because I can't rely on the US government any more.' It isn't unusual for longevity scientists to get involved in the commercial side of the anti-ageing business. Sinclair has helped found numerous biotech companies, financing four of them himself, but so far, his attempts to turn profits have had limited success. According to an investigation published last December by The Wall Street Journal (' A 'Reverse Aging' Guru's Trail of Failed Businesses '), investors have little to show for the more than $US1 billion they have sunk into his start-ups. 'Four companies trying to develop longevity drugs have gone bankrupt or largely halted operations,' the Journal reported. 'Another four either haven't yet tested their drugs or gene therapies in humans or have run only small-scale trials that make it difficult to know whether a drug will work.' In 2011, Sinclair and colleagues started a company called OvaScience, which offered a fertility treatment designed to help older women become pregnant. Its share price tanked after the company admitted that the treatment had failed to improve IVF success rates in patients. In 2017, shareholders sued the company, claiming directors and executives had failed to disclose that the science behind the treatment was untested or in doubt. In Sinclair's defence, scientific progress is rarely made smoothly or easily, says Lindsay Wu, an associate professor of biomedical sciences at the University of NSW. 'Science is risky,' Wu says. 'Most drugs don't get to market.' When I ask Wu to tell me about Sinclair, whom he has known for years, he says: 'He loves science.' Another thing: he is unchanged by fame. 'When everyone wants to talk to him at conferences, he'll seek out an old friend and spend a long time chatting to them. Which I think is a sign of a good person.' On stage at the World Science Festival in Brisbane, Sinclair said he didn't sell or endorse longevity supplements. Yet as the co-founder of Animal Biosciences, he is involved in the sale of a supplement for dogs, marketed under the Leap Years brand. His brother, Nick, is chief executive of the company, which charges $US66 ($102) for a one-month supply for a medium-sized dog. After Sinclair drew flak last year for saying the product was proven to reverse ageing, Animal Biosciences issued an altered press release quoting him as saying it reversed 'the effects of age-related decline in dogs'. Even that seems a stretch to science integrity consultant Elisabeth Bik, who says she found little evidence to support the assertion when she read the research on which it was purportedly based. Loading 'David is basically playing on the emotions of people who want to do the best thing for their dog,' says University of Oklahoma biochemist Professor Arlan Richardson, one of those who quit the Academy for Health & Lifespan Research during the Leap Years kerfuffle. 'I didn't want to be associated with an organisation where the leader was making what I considered to be bogus claims.' His disillusionment is echoed by Brad Stanfield, an Auckland GP with a particular interest in helping patients look and feel younger: he posts YouTube videos on the subject, and markets his own brand of microvitamins. Stanfield says he was dazzled by Sinclair when he saw him on the Joe Rogan podcast: 'He was on the cusp of curing ageing, was the impression that I got. He's a highly credentialled scientist from Harvard, so I just assumed that what he was saying was legitimate.' Stanfield joined the Sinclair fan club. 'I was one of his cheerleaders,' he says. 'It took me about a year to really properly look into David's research without having the rose-tinted glasses. I was bitterly disappointed when I found out the true story.' Sinclair's current championing of NMN seems to Stanfield to be unnervingly similar to his promotion of resveratrol 20 years ago. 'This is a multi-decade pattern of behaviour,' Stanfield says. 'Good scientists are very cautious about their findings. They'll try to disprove their hypotheses. Whereas David seems to want to hype it up.' For light relief, I watch a video of a 2024 podcast featuring Sinclair and English comedian David Walliams. At one point, Walliams says: 'You've had a lot of work done though, no?' Sinclair smiles thinly and says: 'This is all natural.' Walliams (amused): 'You've had a lot of work done if anybody has. Well, you look great.' No single magic bullet The satirical masthead The Onion once ran a story headlined 'World Death Rate Holding Steady at 100 Percent'. That statistic is still correct, and there's no indication that longevity science has done anything to help anyone delay the inevitable. 'How has such an enormous industry flourished for so long with so few actual advances to show for it?' asks Venki Ramakrishnan in Why We Die. The Nobel Prize-winner is dismayed by the amount of hot air that emanates from the anti-ageing field. Sinclair may not officially endorse supplements, Ramakrishnan writes, but he readily declares which ones he takes, and there is no evidence that any of them – resveratrol, NMN or metformin – increase lifespan in humans. None has been tested for this purpose in rigorous clinical trials, and metformin, the diabetes drug, hasn't been approved for use by healthy adults. To advocate their use seems to Ramakrishnan to be 'both ethically questionable and potentially dangerous'. Loading Biochemist Charles Brenner reckons longevity scientists might as well call off the search for a magic bullet. 'Human ageing is not a simple engineering problem,' says Brenner. 'I'm not sure I see any technology emerging that will extend maximum human lifespan.' Ramakrishnan is more hopeful. The explosion in research has certainly increased our understanding of ageing, he says. Sinclair's former colleague, Brian Kennedy, agrees. 'I'm very optimistic,' he says. 'I think things are already happening, basically.' Sinclair is just one person, Kennedy adds. 'Don't let the controversy about David bleed over into the whole field.' Sinclair bursts out laughing when I finally summon the nerve to ask if his preternaturally youthful visage has anything to do with, um, Botox? Fillers? Surgery? How about hair dye? 'No, this is my natural hair colour,' he says. 'I haven't had surgery. I haven't had fillers.' After a pause, he adds: 'I'm proud that I haven't. Because my goal is to be a role model for what a healthy lifestyle can do on the inside and the outside.'

Sydney Morning Herald

an hour ago

Sydney Morning Herald

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

This story is part of the June 14 edition of Good Weekend. See all 14 stories. For a man approaching his 56th birthday, David Sinclair looks to be in excellent shape. Thick, dark hair. Gleaming white teeth. Skin so smooth it's almost spooky. As the celebrated scientist sips matcha green tea at an outdoor cafe on a sunny Sydney morning, I find myself surreptitiously studying his forehead. OK, there are a couple of faint lines, but nothing you could classify as a wrinkle. If he were a used car, you'd say he was in as-new condition. What's his secret? Sinclair's answer is basically that humans, like automobiles, benefit from assiduous maintenance. 'I've always regarded the body as something that you should really take care of,' he says. Caring for the body, specifically holding off the wear and tear associated with ageing, is in Sinclair's case both a personal and professional mission. Australian by birth, he has lived for the past 30 years in the US, where he is a professor of genetics at Harvard Medical School in Boston and a leader in a booming field of scientific endeavour that might be summed up as a quest for eternal youth. The aim is to slow the ageing process in our cells, enabling us to extend our lifespan and, in effect, stay younger for longer. Sinclair takes this a step further, arguing that ageing can be not only delayed, but reversed. Because that's an attractive notion to a lot of people, and because Sinclair makes it sound entirely plausible, his work has brought him money and fame. The Wall Street Journal, which calls him 'the longevity business's brightest star and chief salesman', estimates that investors have pumped more than $US1 billion into biotech enterprises he has spun out of ideas generated in his Harvard laboratory. He has an agent, a publicist, a bestselling book (Lifespan: Why We Age – and Why We Don't Have To), a podcast, more than 1.2 million followers on social media and a calendar filled with speaking engagements. He also has critics. A press release issued last year quoted Sinclair as saying that a company he co-founded, Animal Biosciences, had developed a canine nutritional supplement proven to reverse ageing in dogs. 'That is a lie,' American biologist Matt Kaeberlein responded on X, going on to describe Sinclair as 'the textbook definition of snake oil salesman'. Sinclair said he had been misquoted. Nevertheless, Kaeberlein and others resigned in protest from the Academy for Health & Lifespan Research, a nonprofit organisation co-founded by Sinclair. After a tense meeting of the academy's board, Sinclair relinquished the presidency. To me, he insists that he wasn't pushed out. 'I was going to step down anyway because it was quite a distraction from my research,' he says. 'I didn't have time for the in-fighting.' Sitting with us at the cafe table is Sinclair's partner of four years, Serena Poon. I don't have to ask how he feels about her: I've read his heartfelt tributes on Instagram ('Serena My Love, I feel like the luckiest guy on Earth, having found my perfect match'). Poon, 49, is from California, where she trained as a nutritionist and worked as a private chef – including a couple of years cooking for publisher Hugh Hefner at the fabled Playboy Mansion in Los Angeles. She now bills herself as a 'longevity wellness expert'. She has her own brand, Serena Loves, and sells products such as 'Aura Cleansing Mist with Pure Organic Bulgarian Rose Water' (from $US67 plus postage). Sinclair credits Poon with improving his eating habits: she has weaned him off dairy food and meat, as well as alcohol. It was Poon, too, who introduced him to drinking matcha, which is made from the powdered leaves of tea bushes deprived of sunlight for part of their growing period. The theory is that the resulting stress on the plants produces a brew rich in beneficial antioxidants. 'Every morning we have at least one of these,' Sinclair says, gesturing to the green drink in front of him. That's after he has taken his daily dose of three chemical compounds he believes slow ageing: resveratrol, nicotinamide mononucleotide (NMN) and the diabetes drug metformin. He also swallows vitamins D and K². In other measures aimed at increasing his chances of being around to meet his great-great-grandchildren (to whom he dedicated his book), he sleeps in a bed that lowers his body temperature during the night. He works at a standing desk. He rinses his mouth with coconut oil. He exercises. The dietary changes encouraged by Poon seem to Sinclair to have had visible results. 'You said my skin looks better?' he says, turning to her for confirmation. 'Yes,' she assures him. 'You look younger now than you did when we met.' Gift for overpromising In person, Sinclair is affable and softly spoken. In the spotlight, he morphs into a performer, with a showman's propensity to make sweeping claims ('the first person to live to 150 has already been born') and a habit of presenting himself in a heroic light ('my goal is to save millions of lives'). The flourishes that add colour to his TED Talks and media appearances do not necessarily endear him to fellow scientists. 'David is a gifted storyteller,' says leading biochemist Charles Brenner, based at the City of Hope National Cancer Centre in Los Angeles County. 'He uses rhetorical devices to try to convince people that there is evidence for things that aren't really true.' To some, the most compelling proof of Sinclair's persuasiveness was the decision by pharmaceutical giant GSK – then GlaxoSmithKline – to pay $US720 million for Sirtris Pharmaceuticals, a company he had founded to develop anti-ageing drugs based on resveratrol. Sinclair had only a minor shareholding by the time the purchase was made in 2008 but still collected about $US8 million. (He tells me he can't recall the exact sum.) Eyebrows were raised when GSK stopped resveratrol trials a few years later, having failed to get worthwhile results. 'He pulled off a massive sale of something that didn't work,' says American investigative journalist Scott Carney. Former Harvard Medical School dean Jeffrey Flier has accused Sinclair of failing to acknowledge holes found in his science. 'It's not a good practice to cite a 2006 paper of yours that has been seriously and multiply refuted since then,' Flier said on social media in 2022. When Sinclair responded by blocking communication with him, Flier told followers on X: 'I crossed the line by noticing a major piece of his research was untrue, and I expressed concern that he continued to tout it as true …' Sinclair is a scientific rock star. In 2014, the year he was awarded the Australian Society for Medical Research Medal, Time magazine named him one of the world's 100 most influential people. In 2018, he was appointed an Officer of the Order of Australia (which he tells readers of his book is 'the equivalent of a knighthood'). Earlier this year, at a forum in Berlin, the Cinema for Peace Foundation presented him with something called the Noble Genius Award. In March, he was an honoured guest at the World Science Festival in Brisbane. Researching this story, I start to wonder who and what to believe. Is longevity science the force for good it's cracked up to be, or should I listen to Ukrainian molecular cell biologist Leonid Schneider, publisher of the For Better Science blog, who says 'the whole anti-ageing business is a huge scam'? Is Sinclair a noble genius or, as Scott Carney alleges, 'just the most prominent and successful of the longevity grifters'? Does Sinclair owe his youthful appearance to clean living and anti-ageing supplements or – as online snarks suggest – to hair dye and Botox injections? These questions are playing on my mind as I browse through Sinclair's Instagram account a few days after our meeting in the cafe. In one post, he recommends drinking matcha: 'It helps burn fat when you walk, protects kidneys from damage, improves memory, decreases inflammation and kills cancer cells.' Jeepers. If I'd known that, I'd have had a cup myself. Research race Kicking on to a ripe old age is more common than at any time in human history. In Australia and other high-income countries, the average life expectancy at birth rose by about 30 years in the 20th century, thanks largely to medical advances, vaccination programs and other improvements in public health. But according to a report published last year in the journal Nature Aging, gains in longevity have slowed since 1990 and will probably continue to decelerate as life expectancy approaches a biological ceiling. The report said that, this century, at most 15 per cent of females and 5 per cent of males are likely to reach the age of 100. Unless, of course, scientists can figure out how to slow our bodies' natural rate of decline. We age because our cells gradually deteriorate, functioning less efficiently and losing the ability to repair and renew themselves. What isn't clear is why this happens, and what, if anything, can be done to stop it. In a recent book, Why We Die: The New Science of Ageing and the Quest for Immortality, Nobel Prize-winning molecular biologist Venki Ramakrishnan writes that more than 700 biotech companies with a combined market cap of at least $US30 billion are racing to solve the puzzle. Ramakrishnan notes that tech billionaires Peter Thiel, Elon Musk, Larry Page, Sergey Brin, Jeff Bezos and Mark Zuckerberg have all shown interest in the research. 'And in many cases, they are funding it.' Blogger Leonid Schneider finds something unseemly in the scale of the effort. 'There are a lot of very rich people who know they will die one day and it makes them very sad, because they will be separated from their money,' Schneider says. 'This is where the whole business starts.' Philanthropist Bill Gates has expressed a similar view, pointing out that, in parts of the world, children continue to die from preventable diseases: 'It seems pretty egocentric, while we still have malaria and TB, for rich people to fund things so they can live longer.' Sinclair has a different perspective. For him, he says, the quest is intensely personal. During his childhood on Sydney's upper north shore, he spent a lot of time with his beloved grandmother, Vera, who had fled to Australia after the failure of the 1956 uprising in her native Hungary. (Her only son, Sinclair's father Andrew, changed the family name from Szigeti.) Sinclair was just four when Vera broke the news to him that no one lived forever: she would die one day, as would his parents – both biochemists – and his younger brother. Even the pet cat would die. 'As a four-year-old, that really freaks you out,' Sinclair said on the popular podcast hosted by US comedian Joe Rogan. 'That was a turning point in my life.' Sinclair understood from an early age that Vera expected big things of him. 'She said, 'I'm going to pour love into this child, and make him the vehicle to change the world, to make it a better place.' ' Her message was explicit: 'My grandmother said, 'Do something important.' So I said, 'I'll try to stop people getting old and sick.' I remember the exact moment. I remember where I was, what we were doing, what the carpet felt like.' I end up watching YouTube videos of all three of Sinclair's appearances on Rogan's show. During the first, in 2019, the podcaster says to him: 'You don't have grey hair. That's weird, isn't it? You don't have any?' Later, he asks Sinclair what can be done to mitigate the effects of ageing on the skin. 'You mean besides Botox and stuff?' Sinclair says. Botox isn't an anti-ageing substance, Rogan replies. 'It just freezes your face, like a weirdo.' Rogan can't understand why people use it. Especially males. 'When I see a man whose forehead doesn't move, I want to smack him in the mouth,' he says. Sinclair seems keen to change the subject. 'I don't spend a lot of time thinking about the cosmetic industry,' he says. 'For obvious reasons. I'm trying to save humanity and improve the planet.' A real go-getter When Sinclair enrolled in a science course at the University of NSW in 1987, he was convinced that his would be the last generation whose lives would be limited to the standard length. 'I was obsessing over this, and it was depressing me,' he tells me, recalling an occasion in a campus cafe when he snapped. 'My friends were smoking and drinking beer and playing cards and I just said, 'Stop! Do you realise that we were born one generation too early?' They were like, 'Yeah, whatever, David. Get a drink.' ' At 25, freshly armed with a PhD in molecular genetics, Sinclair bought himself a ticket to Boston. He had landed a job studying ageing in yeast cells in a laboratory at the Massachusetts Institute of Technology. One of his colleagues was Brian Kennedy, now a longevity scientist at the National University of Singapore, who remembers him as a real go-getter – smart, hard-working and 'very aggressive about what he was doing in the lab'. Another colleague was Matt Kaeberlein, who would later call Sinclair a snake-oil salesman but had no complaints about him then. 'He was very supportive, very helpful, a fun guy to be around,' Kaeberlein says. Loading By the age of 30, Sinclair was an assistant professor at Harvard. At 34, he was described in a 2004 article in Science, the journal of the American Association for the Advancement of Science, as 'deeply ambitious, relentlessly competitive, supremely self-confident'. Two years later, Sinclair and his Harvard research team published a paper that said overweight laboratory mice aged more slowly and stayed healthier if fed resveratrol, a plant-derived enzyme found in red wine. Resveratrol activated a protein called a sirtuin, which is involved in metabolic regulation, the paper said, and the sirtuin increased the rodents' longevity. This seemed to tie in with the 'French paradox' – the fact that the citizens of France, who drink a lot of wine, have a relatively low incidence of coronary heart disease despite a diet high in saturated fats. The paper made a major splash. Resveratrol was hailed as a wonder drug and Sinclair was everywhere in the media. When GlaxoSmithKline paid crazy money for his Sirtris Pharmaceuticals in 2008, he appeared to have hit the jackpot, both scientifically and financially. But over the next few years, reputable researchers released studies that disputed Sinclair's claims. They said resveratrol did not, in fact, activate sirtuins: the anti-ageing effect that Sinclair had observed was due to the fluorescent dye used in his experiments. This got much less attention than the original story, but Sinclair was nonetheless hurt and indignant. He told Joe Rogan: 'There were days when I said, 'Screw humanity. I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives.' ' In fact, it wasn't the first time Sinclair's work had been challenged. His former colleagues, Brian Kennedy and Matt Kaeberlein, had tried unsuccessfully to replicate an earlier study in which Sinclair examined resveratrol's impact on ageing in yeast. 'We couldn't reproduce the ability of resveratrol to extend lifespan,' Kaeberlein tells me. After many failed attempts, the pair contacted Sinclair and asked for guidance: what were they doing wrong? 'Basically, we got the runaround,' says Kaeberlein. In 2004, he and Kennedy co-authored a paper that set out their findings: 'We didn't claim there was fabrication of data or anything,' Kaeberlein says. 'We just said, 'We can't reproduce the lifespan effect.' ' Sinclair still maintains he was right about resveratrol and says a study he published i n 2013 confirmed it. A substantial body of evidence contradicts that view. 'Nobody in the ageing field really is studying resveratrol any more,' says Kaeberlein. 'Everybody recognises this was a false lead.' Sinclair insists to me that the work of his laboratory has always been rigorous and accurate. 'None of our theories, none of our papers, have ever been proven wrong,' he says. Ageing action man Vera lived to the age of 92, but she had long been a shadow of her former self. Witnessing his grandmother's frailty in her final years strengthened Sinclair's resolve to save future generations from drawn-out decrepitude. Throwing himself into his research, he formulated a new theory, which is that ageing is caused by damage to the epigenome – the part of our cells that turns genes on or off. 'As we get older, we lose the ability to read our DNA correctly,' he says, and this ultimately causes cells to function abnormally. He argues that by using gene therapy to reprogram our cells, we can erase the corrupt signals that set them on the path to ageing. He gets a laugh at conferences when he says he no longer looks at a person as 'old': 'I just look at them as someone whose system needs to be rebooted.' Sinclair's mother, Diana, was diagnosed with lung cancer at the age of 50. A smoker, she had one lung removed and lived another 20 years, until 2014. In Lifespan, Sinclair writes that his father, Andrew, began to get a bit doddery in his mid-70s. Following Sinclair's example, Andrew started taking NMN, a molecule that converts in the body into nicotinamide adenine dinucleotide (NAD+), which helps build and maintain the structure of cells. Our levels of NAD+ decline with age, Sinclair says. He believes boosting the levels can make cells behave as if they are younger. The way Sinclair tells it in his book, the transformation in Andrew has been astonishing: these days, his father is a veritable action man – the kind of guy who hikes through wind and snow to the peak of Tasmania's highest mountain, goes whitewater rafting in Montana, explores ice caves in Austria. Sinclair told Joe Rogan in 2021 that Andrew had climbed 40 flights of stairs in 15 minutes. 'Holy shit,' Rogan replied. When Andrew visited Boston last year, Sinclair posted a picture on Instagram of the two of them posing with his son (he has three children with his ex-wife, molecular biologist Sandra Luikenhuis). 'Dad's over from Australia for his 85th birthday,' Sinclair wrote. 'He is a machine. No jet lag and fitter than Ben and me.' On meeting Andrew in Sydney, I ask for his own account of how the NMN has affected him. 'Probably gives you more energy,' he says mildly. A while later, in April, I see that Sinclair has posted a photograph of himself and Andrew at the top of the Sydney Harbour Bridge, which they had climbed. In his caption, Sinclair has again portrayed Andrew as freakishly hale and hearty: 'He doesn't even need glasses to drive at night!' Examining the picture, I register that in one respect at least, Andrew is a normal 85-year-old: the small amount of hair left on his head is silver-grey. The contrast with Sinclair's luxuriant dark locks is striking. Reputation for hyperbole On Sinclair's social media accounts, happy snaps of his family and laboratory staff are interspersed with startling scientific announcements. 'Age reversal works in primates to restore vision,' he tweeted in April 2023. '… Next up: age reversal in humans.' Three months later, he declared: 'This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating age-related diseases.' The post got the attention of the world's richest man, Elon Musk, who responded: 'OK, so what exactly is it?' Others, aware of Sinclair's reputation for hyperbole, urged caution. 'Many reasons to be concerned about these claims,' wrote Jeffrey Flier, the former Harvard dean. Matt Kaeberlein kept his comment short: 'Nobody has a drug to reverse aging.' Not yet, Sinclair concedes. But he is confident that, thanks to the cell-reprogramming gene therapy invented in his laboratory and developed by a company he chairs, Life Biosciences, such a drug is on the way. The therapy has been used to restore sight in monkeys, he tells me. 'Early next year we hope to treat the first blind human patient with this technology. If that works, I will be happy to say that, yes, we can rejuvenate parts of humans. And ultimately the whole body.' Think of the way a salamander regrows a limb, he says. If they can do it, why can't we? 'I believe we've uncovered that mechanism, which we've lost over time.' This idea turns anti-ageing science on its head, says Tristan Edwards, the Australian former hedge-fund manager who founded Life Biosciences with Sinclair in 2016. In the main, longevity researchers have concentrated on extending our productive lifespan by building our resistance to the ailments of old age, Edwards says. 'Now the focus is on having everyone just regenerate and be young and healthy indefinitely. If everyone is essentially 25 for a thousand years, you don't need to worry about Alzheimer's any more. Cardiovascular disease isn't a thing.' Life Biosciences chief executive Jerry McLaughlin, who has travelled extensively with Sinclair, reports that he is recognised all over the world. Not long ago they were having a snack in a Marriott hotel in Saudi Arabia when they realised that the two other people in the lounge were staring at the scientist. 'I feel for him sometimes,' McLaughlin says. 'It's part of the price you pay for doing such wonderful work.' Bogus claims He isn't in it for the money. Sinclair would like to make that clear. 'People think I'm a multimillionaire, living the high life,' he says. What they don't realise is that he has ploughed almost everything he has earned back into his work: 'I would rather fund medical research and clinical trials than own a house.' He does have a weekender at Cape Cod, but it's mortgaged, he says. He rents his apartment in Boston. 'I don't want to die rich. I don't even want my kids to die rich. I want to fulfil the mission.' US President Donald Trump has threatened a $US3 billion ($4.6 billion) cut in federal funding to Harvard, the oldest and wealthiest university in the country. Sinclair expects his lab to lose grants worth about $US2 million, which will mean halting some research projects. 'It's a tragedy,' he says. 'It's forcing me to focus on generating revenue that I can funnel into research because I can't rely on the US government any more.' It isn't unusual for longevity scientists to get involved in the commercial side of the anti-ageing business. Sinclair has helped found numerous biotech companies, financing four of them himself, but so far, his attempts to turn profits have had limited success. According to an investigation published last December by The Wall Street Journal (' A 'Reverse Aging' Guru's Trail of Failed Businesses '), investors have little to show for the more than $US1 billion they have sunk into his start-ups. 'Four companies trying to develop longevity drugs have gone bankrupt or largely halted operations,' the Journal reported. 'Another four either haven't yet tested their drugs or gene therapies in humans or have run only small-scale trials that make it difficult to know whether a drug will work.' In 2011, Sinclair and colleagues started a company called OvaScience, which offered a fertility treatment designed to help older women become pregnant. Its share price tanked after the company admitted that the treatment had failed to improve IVF success rates in patients. In 2017, shareholders sued the company, claiming directors and executives had failed to disclose that the science behind the treatment was untested or in doubt. In Sinclair's defence, scientific progress is rarely made smoothly or easily, says Lindsay Wu, an associate professor of biomedical sciences at the University of NSW. 'Science is risky,' Wu says. 'Most drugs don't get to market.' When I ask Wu to tell me about Sinclair, whom he has known for years, he says: 'He loves science.' Another thing: he is unchanged by fame. 'When everyone wants to talk to him at conferences, he'll seek out an old friend and spend a long time chatting to them. Which I think is a sign of a good person.' On stage at the World Science Festival in Brisbane, Sinclair said he didn't sell or endorse longevity supplements. Yet as the co-founder of Animal Biosciences, he is involved in the sale of a supplement for dogs, marketed under the Leap Years brand. His brother, Nick, is chief executive of the company, which charges $US66 ($102) for a one-month supply for a medium-sized dog. After Sinclair drew flak last year for saying the product was proven to reverse ageing, Animal Biosciences issued an altered press release quoting him as saying it reversed 'the effects of age-related decline in dogs'. Even that seems a stretch to science integrity consultant Elisabeth Bik, who says she found little evidence to support the assertion when she read the research on which it was purportedly based. Loading 'David is basically playing on the emotions of people who want to do the best thing for their dog,' says University of Oklahoma biochemist Professor Arlan Richardson, one of those who quit the Academy for Health & Lifespan Research during the Leap Years kerfuffle. 'I didn't want to be associated with an organisation where the leader was making what I considered to be bogus claims.' His disillusionment is echoed by Brad Stanfield, an Auckland GP with a particular interest in helping patients look and feel younger: he posts YouTube videos on the subject, and markets his own brand of microvitamins. Stanfield says he was dazzled by Sinclair when he saw him on the Joe Rogan podcast: 'He was on the cusp of curing ageing, was the impression that I got. He's a highly credentialled scientist from Harvard, so I just assumed that what he was saying was legitimate.' Stanfield joined the Sinclair fan club. 'I was one of his cheerleaders,' he says. 'It took me about a year to really properly look into David's research without having the rose-tinted glasses. I was bitterly disappointed when I found out the true story.' Sinclair's current championing of NMN seems to Stanfield to be unnervingly similar to his promotion of resveratrol 20 years ago. 'This is a multi-decade pattern of behaviour,' Stanfield says. 'Good scientists are very cautious about their findings. They'll try to disprove their hypotheses. Whereas David seems to want to hype it up.' For light relief, I watch a video of a 2024 podcast featuring Sinclair and English comedian David Walliams. At one point, Walliams says: 'You've had a lot of work done though, no?' Sinclair smiles thinly and says: 'This is all natural.' Walliams (amused): 'You've had a lot of work done if anybody has. Well, you look great.' No single magic bullet The satirical masthead The Onion once ran a story headlined 'World Death Rate Holding Steady at 100 Percent'. That statistic is still correct, and there's no indication that longevity science has done anything to help anyone delay the inevitable. 'How has such an enormous industry flourished for so long with so few actual advances to show for it?' asks Venki Ramakrishnan in Why We Die. The Nobel Prize-winner is dismayed by the amount of hot air that emanates from the anti-ageing field. Sinclair may not officially endorse supplements, Ramakrishnan writes, but he readily declares which ones he takes, and there is no evidence that any of them – resveratrol, NMN or metformin – increase lifespan in humans. None has been tested for this purpose in rigorous clinical trials, and metformin, the diabetes drug, hasn't been approved for use by healthy adults. To advocate their use seems to Ramakrishnan to be 'both ethically questionable and potentially dangerous'. Loading Biochemist Charles Brenner reckons longevity scientists might as well call off the search for a magic bullet. 'Human ageing is not a simple engineering problem,' says Brenner. 'I'm not sure I see any technology emerging that will extend maximum human lifespan.' Ramakrishnan is more hopeful. The explosion in research has certainly increased our understanding of ageing, he says. Sinclair's former colleague, Brian Kennedy, agrees. 'I'm very optimistic,' he says. 'I think things are already happening, basically.' Sinclair is just one person, Kennedy adds. 'Don't let the controversy about David bleed over into the whole field.' Sinclair bursts out laughing when I finally summon the nerve to ask if his preternaturally youthful visage has anything to do with, um, Botox? Fillers? Surgery? How about hair dye? 'No, this is my natural hair colour,' he says. 'I haven't had surgery. I haven't had fillers.' After a pause, he adds: 'I'm proud that I haven't. Because my goal is to be a role model for what a healthy lifestyle can do on the inside and the outside.'

Is it too easy to get a prescription for medicinal cannabis?

ABC News

2 hours ago

ABC News

Is it too easy to get a prescription for medicinal cannabis?

There are concerns people are getting their hands on medicinal cannabis to treat conditions where there's very little evidence of benefit — and the possibility of harm. Also, why weight loss drugs could improve treatment for people with schizophrenia. The full breadth of corporate ownership of radiology clinics is revealed. And what questions need to be asked with IVF in the spotlight, as Monash IVF deals with the fallout from a second bungled embryo transfer. References:

Australian IVF mix up ‘probably not the first time'

Hashtags

Try Our AI Features

Comments

Related Articles

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

Is it too easy to get a prescription for medicinal cannabis?

Australian IVF mix up ‘probably not the first time'

Hashtags

Try Our AI Features

Comments

Related Articles

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

Never say die: A controversial Harvard-based Aussie's hunt for the fountain of youth

Is it too easy to get a prescription for medicinal cannabis?

Get Started Now: Download the App