Will 2025 be the year that “age reversal” enters the medical mainstream? Is the fountain of youth about to become bigger than the Victoria Falls this year?
Probably not, since scientists can’t even agree on what “age reversal” actually means. That’s despite significant advances in age-reversal medicine and its close cousin, longevity medicine.
Longevity medicine focuses broadly on extending lifespan and “healthspan”, the term for improving health and adding quality to years left to live, without necessarily claiming to “reverse ageing”. Age-reversal medicine focuses more on reversing biological ageing processes, with the possibility of returning cells or tissues to a more youthful state.
Longevity medicine has its scientific challenges. However, it is not plagued by the myriad ethical challenges that hamper progress in age-reversal medicine. As a scientific concept, age reversal is now so mired in controversy, semantic skulduggery, research challenges and ethical dilemmas that some scientists say it no longer has any meaning.
They say that it is worsening rising levels of public distrust in science and highlighting the urgent need for improved communication strategies. They are calling for a new term to replace age reversal. Quite what it should be is not yet clear.
What is clear is one of the main drivers of controversy swirling around age-reversal science: prominent researchers who muddy the semantic and scientific waters with controversial claims that don’t stand up to scientific scrutiny. Exasperated peers are calling them “rogue scientists”, “snake oil salesmen” and purveyors of “exciting bullshit”.
They have aimed their harshest epithets squarely at the professional solar plexus of Harvard Medical School tenured genetics professor David Sinclair. Sinclair is one of the most prominent members of the age-reversal fraternity in the US. There are other prominent scientists globally in fields allied to longevity medicine in critics’ line of fire, among them, Japanese stem-cell researcher and Nobel laureate Dr Shinya Yamanaka.
There’s good reason that critics give Yamanaka an easier time than Sinclair. Yamanaka works at the Centre for iPS Cell Research and Application at Kyoto University in Japan. He holds the position of director emeritus and professor and is primarily recognised for his groundbreaking discovery of induced pluripotent stem cells (iPSCs). It has had profound implications for regenerative medicine and ageing research.
The discovery has enabled the generation of iPSCs from adult tissues without the ethical concerns associated with embryonic stem cells. In 2012, Yamanaka won the Nobel prize in physiology or medicine for his work, along with distinguished British developmental biologist Dr John Gurdon.
The prize consolidated Yamanaka’s position as a highly respected figure in the scientific community. His work on iPSCs has revolutionised regenerative medicine. However, Yamanaka has also faced criticisms for this research, particularly concerning associated cancer risk and immune system dysfunction.
While iPSCs do avoid ethical dilemmas associated with embryonic stem cells, concerns persist regarding the manipulation of human cells and the potential for unintended consequences in gene-editing practices. A major buffer for Yamanaka against criticism is that his work is grounded in rigorous scientific methodology and has been widely replicated. Unlike Sinclair’s.
Sinclair’s position at Harvard has provided institutional support and credibility. His academic pedigree has also helped. He is among the most prolific of age-reversal scientific authors with just more than 400 publications, mostly in peer-reviewed journals, and about 71,811 citations to his credit. Yamanaka has 300 publications to his credit, though with a higher citation rate at more than 100,000.
Both Sinclair and Yamanaka are acknowledged as having made significant contributions to the understanding of ageing. Sinclair has set himself apart by becoming the poster boy for age reversal’s scientific, ethical and other ills. His precipitous fall from scientific grace lies not just in scientific perspectives on ageing. An aggravating factor is the semantics of science — the variability of language scientists use to talk about it. It bears brief examination.
Ageing is, after all, a perfectly natural process. It is multifactorial, influenced by genetics, environment, lifestyle and individual health. It involves complex, interrelated internal processes, including cellular damage, genetic changes and metabolic decline. Some scientists see ageing as a series of biological changes leading to senescence.
Senescence is the natural process of biological ageing by which living organisms, including humans, gradually lose their ability to function well over time. It’s the reason for greying hair, wrinkles, declining cognitive function and increased vulnerability to disease. Senescence lies at the heart of why Sinclair and other scientists see ageing as a disease in itself, one that can be reversed or cured with the right targeted treatment.
Sinclair has demonstrated commitment not only to understanding the biological mechanisms of ageing but also to working actively towards reversing its effects. He has suggested that if medical science can just “reset” ageing in organs, it might be able to eliminate diseases associated with ageing altogether.
Other scientists take a more nuanced, multifactorial view of ageing as a more complex process. They characterise it as the accumulation of cellular damage or epigenetic changes.
A confounding factor in the controversy is that age-reversal medicine extends beyond reversing internal ageing processes and disease to encompass strategies for achieving a more youthful external appearance. Sinclair’s work and leanings tap directly into cultural narratives — some would say obsessions — with eternal youth.
At age 53 and with a wrinkle-free face, Sinclair is a good advertisement for what he preaches. He promotes the idea that lifestyle changes, supplements and, potentially, gene therapies can slow or reverse ageing processes. He has regularly claimed to have “knocked more than two decades off [his] biological age”.
His popular book, Lifespan: Why We Age, And Why We Don’t Have To, and public persona as a “longevity guru” have further fuelled interest in his work. They tap directly into societal desires and fantasies about eternal youth and health.
Yamanaka’s research is most often viewed through a scientific lens rather than a cultural one. His contributions have proved transformative in the realm of regenerative medicine but less focused on the quest for youthful immortality.
His approach emphasises ethical considerations and potential for treating age-related diseases rather than sensational claims about halting or reversing ageing itself. This scientific rigour has garnered respect from peers, making them less likely to criticise him harshly. It especially inoculates him against personal attack.
Conversely, and unsurprisingly, Sinclair’s reliance on anecdotal evidence and speculative claims, coupled with his entrepreneurial bent and enthusiasm for commercialisation of his research has drawn significant criticism from peers who prioritise empirical validation.
One of his fiercest critics is top US biochemist Dr Charles Brenner, an award-winning researcher in the longevity field and chair in diabetes and cancer metabolism in the department of diabetes and cancer metabolism of the City of Hope National Medical Centre. As a recently avowed “longevity sceptic”, he is the perfect foil to Sinclair’s image as a “longevity guru”.
Brenner has worked closely with Sinclair and is scathing about him. He calls Sinclair’s Lifespan book “an important and influential source of disinformation”. He calls Sinclair a “fabulist” — and worse.
Sinclair first became known for his research in the early 2000s on resveratrol, a compound found in red wine. He claimed research data showed that the compound could activate specific molecules called sirtuins that could extend lifespan in model organisms, such yeast and mice.
Sirtuins are a family of seven proteins with enzymatic activity. They are often referred to as “the guardians of the genome” as they help maintain the integrity of our genetic material by protecting our DNA. They also support the regulation of various biological processes related to metabolism, cellular health and how we age.
Sinclair’s assertion about the ability of resveratrol to stimulate sirtuins became a cornerstone of his claims about its ability to promote longevity. He told audiences at media events: “If you drink red wine, you’re getting a little bit of resveratrol, which is good for you.”
Critics pointed out that the amount of resveratrol in red wine was relatively low and unlikely to produce the effects he was promoting. They criticised him for making false claims, contributing to misinformation in longevity research and creating unrealistic expectations among the public regarding efficacy of resveratrol and similar compounds.
Sinclair responded by making increasingly bold statements about resveratrol, calling it “as close to a miraculous molecule as you can find”. He suggested that it could prevent age-related diseases, such as heart disease, stroke and cancer. He predicted that in the future people might take such compounds daily to enhance health and longevity.
In 2004, Sinclair founded Sirtris Pharmaceuticals. He focused the company on developing therapies based on his resveratrol research. He claimed that the lead compound the company developed, a formulation based on resveratrol, could mimic the effects of caloric restriction and potentially extend lifespan and improve health.
Brenner was on the Sirtris scientific advisory board. In an interview, he described the experience as “an eye-opener” that was not positive.
In 2008, GlaxoSmithKline (GSK) acquired Sirtris for $720m, making Sinclair suddenly very rich. The acquisition was initially seen as a validation of his research and marked a significant moment in Sinclair’s career.
However, the substantial financial stakes involved raised concerns about Sinclair’s motivations. Scientists who struggled to replicate Sinclair’s findings on resveratrol’s effects on sirtuins began taking jaundiced looks in his direction.
Critics contended that Sinclair had selectively reported findings favouring resveratrol, while downplaying or ignoring studies questioning its efficacy. They accused him of overhyping his research data to inflate resveratrol’s value and to secure the lucrative deal by making the acquisition look more attractive to GSK.
In other words, critics accused Sinclair of prioritising commercial success over scientific integrity. Those criticisms grew louder once Amgen and Pfizer scientists began challenging the validity of Sinclair’s claims further after being unable to replicate his findings.
GSK shut down Sirtris in 2014 after disappointing results and a dearth of definitive evidence of efficacy in humans for age reversal or related conditions. Information since has shown that most GSK scientists vehemently opposed the acquisition from the outset on the basis of a critical lack of evidence of efficacy in humans.
GSK has faced scrutiny regarding its investment decisions. It has acknowledged challenges in its R&D strategy over the years without explicitly stating regret or embarrassment at having spent close to a billion dollars to acquire Sirtris.
“Marketing won out,” one critic said.
The closure of Sirtris knocked some of the gloss off Sinclair’s reputation but he speedily bounced back. He focused attention on his research into nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme found in all living cells that plays a vital role in various metabolic processes.
After Sirtris, Sinclair founded several other companies (about 20, according to some reports). Many have struggled or failed. These ventures have reflected a pattern, say critics, of ambitious promises from Sinclair followed by disappointing outcomes.
Critics have consistently accused him of promoting supplements and treatments without adequate evidence of efficacy and safety, potentially misleading and endangering the public. They have raised ethical concerns about potential conflicts of interest from Sinclair’s involvement in commercial ventures related to his research.
Sinclair may have taken his biggest step too far in 2024 with claims that his newest company, Animal Biosciences, had developed a supplement based on NAD+ that could “reverse ageing” in dogs. This sparked the most significant backlash yet. It also precipitated a flood of resignations from the Academy for Health and Lifespan Research, that Sinclair cofounded with Dr Nir Barzilai.
Barzilai, director of the Institute for Ageing Research at the Albert Einstein College of Medicine and another prominent figure in the age-reversal field, reportedly said of Sinclair’s claim: “The data is not good, you’re calling it the wrong thing and then you’re selling it. The selling is a step too far.”
Among those who resigned, as a result, from the Academy for Health and Lifespan Research, was Dr Matt Kaeberlein, a prominent US biogerontologist and researcher specialising in the biology of ageing and age-related diseases.
Kaeberlein is professor of laboratory medicine and pathology at the University of Washington. He is also co-director of the Dog Ageing Project, a large-scale study aimed understand ageing in dogs and exploring interventions, such as rapamycin, to extend their healthspan. The project is unique in studying pet dogs as models for human ageing and longevity.
He took strong exception to Sinclair’s claim about reversing ageing in dogs. In his resignation statement on X, Kaeberlein cited Sinclair’s behaviour that he found “both personally and professionally unacceptable”.
He also found it “deeply distressing that we’ve gotten to a point where [dishonesty] in science is normalised to an extent that nobody is shocked when a tenured Harvard professor falsely proclaims in a press release that a product he is selling to pet owners has ‘reversed ageing in dogs’,”.
Kaeberlein called Sinclair’s claim “textbook definition of snake oil salesman”.
Sinclair was only relatively remorseful. He claimed to have been misquoted and promised to be “more mindful in future” of his words.
Animal Biosciences changed statements and wording in press releases to say that the supplement could “reverse the effects of age-related decline” in dogs rather than claiming to reverse ageing outright. That shift looked more like damage control than any attempt to address concerns around Sinclair’s original claims.
Sinclair is unrepentant. He has insisted that all his research is grounded in solid science. He has argued that while some findings may not be replicated immediately or may face scepticism, that is just normal cut and thrust of scientific progress.
Sinclair has retained his position at Harvard — despite the controversies and criticisms, while most likely laughing all the way to the bank. The most pressing reason for Harvard keeping their man is probably the financial implications of his work, including funding in the billions from his ventures. Harvard is likely to have benefited financially from Sinclair’s sale of Sirtris through potential royalties, increased funding for his laboratory, enhanced institutional prestige and new collaboration opportunities, contributing to its standing in the field of biomedical research.
Tenured professors at Harvard also enjoy protections under the university’s statutes. These stipulate that professors can be removed only for serious infractions. This high threshold for dismissal means that even serious allegations may not lead to immediate action unless substantiated through formal investigations.
In Sinclair’s case, critics of his resveratrol research have primarily categorised it as “bad science” rather than outright, scientific fraud. That distinction is critical; allegations of scientific misconduct typically require clear evidence of fabrication, falsification or plagiarism, which have not so far been substantiated against Sinclair.
Brenner has some famous last words and a bottom line to give in an interview on the future of longevity and ageing research, published on CTech, an arm of the Israeli daily business and economics website, Calcalist. In it, he says that he does not foresee technological developments that would significantly extend maximum life expectancy, and he definitely does not foresee eternal life becoming a reality.
“Scientists who promote such innovations greatly exaggerate the ability to extend life expectancy, and they will continue to promise too much and deliver too little,” Brenner says. “Instead of chasing age reversal, we need to focus on healthy ageing — to live in good health into our 90s and 100s.”
Amen to that.
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