As a tenured professor of biology and genetics at Harvard Medical School, David Sinclair has long been the world’s most qualified “biohacker”. The term refers to a broad community that attempts to enhance bodily performance, sometimes through simple treatments like meditation. But some of its advocates go much further. Sinclair himself has turned his body into a walking laboratory to test his controversial thesis: that ageing itself is a treatable disease.

Looking incredibly young has certainly helped his case — even now, at 54, Sinclair could still pass for a 30-something. A decade ago, Time featured Sinclair on its annual list of the world’s most influential people. And by popularising the concept of “autophagy”, Sinclair has almost certainly influenced you at some point.

Autophagy, which comes from the Greek for “self-devouring”, refers to the process by which cells deprived of fresh supplies of glucose are forced to “feed off” themselves, reducing the inflammatory toxins that are so synonymous with ageing and, in theory, revitalising the mitochondria that power every cell. While Silicon Valley tech bros such as Brian Johnson, Peter Thiel and Jeff Bezos may have garnered more headlines, a lone maverick scientist, in science-fiction style, was busy working on the medical secret to substantiate their quest for eternal youth. Or so it seemed.

Nowadays, former colleagues in academia are queueing up to denounce Sinclair. In March, when he announced with his brother that their company Animal Bioscience had developed a supplement for dogs “shown to reverse the effects of age related decline”, it proved to be the final straw. A former research partner, and colleague at Harvard Medical School, labelled him “the textbook definition of snake-oil salesman”, before Sinclair resigned from his role as President of the Academy for Health and Lifespan Research on 13 March.

So where did it all go so wrong for Sinclair? After all, it’s not as though Time were wrong to cite his influence — which has become ubiquitous by stealth. With the unmasking of one of its leaders, where next for the biohacking movement? And is there more to it than billionaire daydreams and sketchy online apothecaries?

In many ways, it simply continues to grow. Because calorie restriction has been consistently shown to increase lifespan in laboratory animals, Sinclair’s championing of autophagy to stabilise lower blood sugars has seeped into popular consciousness as a rationale for weight-loss “hacks” that might also help you live longer. Advocates of intermittent fasting, buttered coffee, ultra-low carb diets, cold-water immersion or drinking diluted vinegar invariably invoke the implied cloak of scientific legitimacy that autophagy provides. And Sinclair personally aligned himself and his clout with these sorts of trends. By taking just one meal and 1,100 calories per day, and focusing on plant-based, low-carb, low-protein, and heart-healthy high-fat foods, he promoted the “deep cleanse” cellular repair and ultimate detox that autophagy is meant to provide. In turn, autophagy is in large part responsible for the popularity of the so-called 16:8 diet, whose adherents consume their calories in an eight-hour window before fasting for the next 16 to maintain low-blood sugars.

So, when the American Heart Foundation published research last month indicating that restricted-eating-window diets of the 16:8 variety were linked to 91% higher risk of cardiovascular deaths, they rattled many of the intermittent fasting advocates. But Sinclair had already been testing the scientific establishment’s patience for years. By suggesting that non-diabetics should consider taking the diabetes drug Metformin, for longevity purposes, as he did, Sinclair had long courted controversy, and not just from outside of the biohacking community but from within it.

Because if Sinclair is the father of anti-ageing biomedicine, Oedipal forces have been massing against him for some time. On 10 March, Dr Brad Stanfield, another noted longevity influencer, launched a withering takedown of his career and record. Stanfield alleged that by setting up companies trading in anti-ageing supplements of dubious merit, Sinclair amassed a personal fortune. Initially, it was resveratrol, the much hyped “miracle” compound found in red wine. According to Stanfield, GlaxoSmithKline bought the rights to the research for $720 million dollars and spent five years trying and failing to replicate Sinclair’s findings. More recently, again without compelling clinical evidence from human trials, Sinclair has been advocating for and marketing the supplement NMN to boost NAD+ levels, in order — he said — to encourage DNA repair and enhance insulin sensitivity.

Such internal feuding demonstrates the reality of the biohacking movement. Because, while the public has a tendency to conflate longevity science with plutocrats obsessed with living forever, the movement is far from an elite project. Many biohackers are in late-middle age and have more grounded expectations. When I meet John Hemmings, a 63-year-old biohacker, he explains that by extending his “healthspan” he hopes to “compress his morbidity” and delay the onset of age-related conditions such as heart disease, diabetes, cancer and, in particular, Alzheimer’s. Hemmings is hardly your average subject matter — in an earlier political career, he was a Lib Dem MP who used parliamentary privilege to denounce Ryan Giggs’s attempts to use a super-injunction to silence press coverage of his private life. But in other ways, Hemmings’s anxieties are representative, given that, on average, senior citizens rack up five separate comorbidity diagnoses by the age of 80. It’s easy to see why some might seek more control over their exit strategy.

Hemming’s new career as a committed biohacker began in earnest in 2020 when, at 21 stone, he realised that was a likely candidate for type 2 diabetes. He managed to lose seven stone in just nine months (a process he broadcast on social media) by making use of a device designed for diabetics. A skin sensor allowed him to perform continuous glucose monitoring (CGM) and track his blood sugar in real time through an app. For the first time he could see how levels spiked and fell in relation to different meals and activities. Preventing spikes means eliminating the crashes that inevitably follow, which reduces hunger pangs and helps weight loss. And CGM is the most prevalent biohacking trend of the moment. For many, weight loss is the primary goal, but for others, like Hemmings, it’s a gateway to biohacking through which the ultimate prize of a longer, healthier life first becomes visible. That higher glucose levels act as an ageing accelerator is the central premise of the longevity community, but Hemmings quickly realised its limitations. “It’s not as if there is just one number that matters. It requires a holistic approach.”

Today, he spends around £10,000 a year on weekly blood tests to track the effects of his various interventions on key biomarkers as a way of stalling ageing at a cellular level. And he is now a convert-turned-preacher: he publishes blogs replete with homespun microbiological research that track the impact of his treatments. More radically, these include rapamycin, which Hemmings sources from India. Although it’s a potentially harmful immunosuppressant used to prevent the rejection of kidney transplants, rapamycin has also been shown to extend lifespans in animal trials and is the longevity community’s greatest hope of a “quick win” against ageing. Hemmings believes rapamycin is likely to be a more effective method than fasting when it comes to inducing that all important state of autophagy.

He monitors his long-term progress through epigenetic tests — a type of biochemical assessment that looks at DNA to see how well cells are ageing in relation to their chronological age (he proudly tells me that one put his age at 53, and another at just 36). But with his political background, Hemmings sees his personal travails as heralding social change. He believes that our health service is out of date because it is predicated on repairing the damage caused by our afflictions, by which time it’s often already too late. “Biohacking enables people to have detailed information as to what they can do to improve how their bodies function in the short term. Hence rather than waiting to get ill and then going in and out of health care, the level of personal health can be maintained,” he says.

Despite all the money he has spent, Hemmings represents the grassroots of the biohacking movement — those seeking their own routes to longevity. And he has long been sceptical of figures like Sinclair: “The science just isn’t strong enough to support some of the claims he’s been making.” Instead, it is other leading longevity podcasters such as Dr Peter Attia and the newly emergent voice of Dr Stanfield who are likely to benefit from Sinclair’s defenestration. As a practising GP in Auckland, with clinical expertise in helping people age gracefully, Stanfield in particular has become Sinclair’s online nemesis.

“What works for laboratory rodents doesn’t necessarily apply to large mammals like human beings.”

Both Stanfield and Attia are physicians, and appear comparably mindful of their Hippocratic responsibility to, first, do no harm. Both tend to wait until multiple clinical studies converge around similar findings before recommending supplements. And both have identified the worrying tendency of longevity researchers such as Sinclair to conflate the evidence from animal and human trials. Looked at independently, the evidence from human trials alone often tells a very different story. And Sinclair’s entire theory of autophagy may well prove to be a classic example of this pattern. What works for laboratory rodents doesn’t necessarily apply to large mammals like human beings. Stanfield cites evidence suggesting that humans would need to fast for four days to derive the autophagy benefits that can be induced in mice in just 16 hours.

Like Attia, Stanfield regards autophagy as a dangerous distraction, and beyond short-term weight loss, he contests the idea that calorie restriction and fasting has any long-term longevity benefits, a stance now echoed by the American Heart study. What’s more, depriving your body of vital nutrients like protein for 16 hours a day is a high-risk strategy, given that human studies show that frailty is the commonest factor in all-cause mortality. As Attia argues, unless we mitigate “sarcopenia”, the age-related loss of skeletal muscle mass and strength which normally begins in our 30s, ultimately frailty will be our undoing — even if it’s not listed on our death certificates.

By advocating fasting and low-protein intake, Sinclair has been flying in the face of preventative care clinical guidelines for years. It seems that you can be a serious research scientist or an entrepreneur, but not both (and by pushing supplements for dogs, Sinclair appears to have opted for neither). But perhaps the work of more serious figures like Attia and Stanfield shows that what we currently call biohacking could ultimately become part of general medical treatment. Given that the global market for anti-ageing biomedicine is projected to be worth $93 billion by 2027, they are certainly unlikely to be the last to try and realise its immortal temptations.

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Source: UnHerd Read the original article here: https://unherd.com/