Telocyte founder discusses new book and reveals plans to initiate telomerase gene therapy trial in dogs this year.
As longevity biotech Telocyte continues its efforts to develop a telomerase gene therapy aimed at reversing Alzheimer’s pathology at the cellular level, the company’s founder Michael Fossel is making the case that the field has been asking too little of itself for too long. Fossel’s newly published book, Reversal: Science, Medicine, and a Future Beyond Aging, sets out the thesis that aging should not be treated as an inevitable slide into damage control, but as a biological process that can be understood well enough to intervene upstream, potentially resetting cellular function rather than merely slowing decline.
Longevity.Technology: Fossel’s latest work arrives at a moment when interest in age-reversal science is accelerating but consensus on the best path forward remains elusive. He proposes that the real medical opportunity is not simply to manage the diseases of aging one by one, but to confront the aging process that gives rise to them. While that principle in many ways underpins what longevity biotech should be all about, Fossel argues that much of today’s sector is still stuck in what he calls “short-gevity” – chasing marginal improvements instead of true reversal. We sat down with the scientist, author and entrepreneur to find out more.
With Telocyte having finally secured the investment needed to move forward with its clinical development plans, Fossel said the long wait inspired him to put his thoughts on the longevity field down in writing.
“We’ve been as patient as we can be for the longest time,” he says. “Instead of twiddling my thumbs, I thought, why don’t I put together this book? What I’m really saying in the book is that almost everything we’re doing in the longevity community has been focused on what I call short-gevity. That is: how can we make people healthier for a few more years? Which is admirable, but the model is biologically flawed. Age reversal is the only viable path for effective therapy.”
Aging doesn’t ‘just happen’
Fossel argues that longevity biotech should be aiming for something much more profound – scientifically, medically, socially and economically.
“I think what we can do is actually show that we can reverse human aging – not just in cells and tissues and to some extent animals, the way we’ve done in the past – but in human trials,” he says. “The outcome of that will have more impact than probably any other paradigm shift: fire, agriculture, industrialization, computers, maybe even AI – certainly microbial disease did. Because what we’re talking about is doubling or tripling the normal human healthy lifespan by being able to cure and prevent essentially all age-related diseases.”
According to Fossel most people still assume that aging “just happens” – that our biology naturally declines over time, and the most we can do about it is to slow the decline down.
“I understand that view, but it’s not borne out when you look carefully at the scientific evidence,” he says. “What the evidence suggests is that things don’t just go downhill – they go downhill because maintenance fails. The question is: can we reset that maintenance?”
A few companies, including Telocyte, are betting that the answer to that question is yes – at least to some extent. And Fossel is keen to find out what that extent is.
“There will be both conceptual and technical obstacles ahead of us,” he says. “We don’t know what they are yet. There are bound to be surprises. But yes, I think we can pull this off. My best wish would be to get this through the FDA and show that we’re actually capable of doing this in human beings. Beyond that, I’d like to see other people do it as well. The key outcome is simply to do it – regardless of who does it.”
‘We need a Wright brothers moment’
By way of an analogy, Fossel reflects on Lord Kelvin’s famous words in 1895, when he claimed that heavier-than-air flying machines were “impossible.”
“Back then, you might try to come up with the best hot-air balloon you could,” says Fossel. “So even if you had AI and quantum computing, you might still have been perfecting the hot-air balloon rather than building the Wright brothers’ airplane.”
“In the same sense, when it comes to aging we need a Wright brothers moment. I think we’re being a little too near-sighted in what we’re looking at. We’re trying to get small gains. If we stepped back and re-examined our assumptions, I think we could do a lot better.”
Using Alzheimer’s as an example, Fossel describes progress in drug development as focusing largely “downstream”.
“We tried drugs to decrease agitation or aggression and drugs to help memory,” he says. “Then you got therapies targeting beta-amyloid, like lecanemab and similar antibodies. That’s a step closer to the cause rather than the symptom. But even that raises a deeper question: if beta-amyloid is involved, what caused the beta-amyloid accumulation? So you’re still only one step upstream.”
According to Fossel, the same approach has largely been adopted when it comes to aging.
“Take the 12 classic hallmarks of aging,” he says. “In a sense they’re symptoms and signs. They’re important because they let you measure outcomes. You need biomarkers to say: here’s what we measured, here’s what changed. But it’s not clear that any of those are causal. They may be downstream effects.”
Of course, at the opposite extreme there are also approaches targeting upstream risk factors, such as people with two copies of APOE4, who are known to have a much higher risk of Alzheimer’s.
“You could attempt gene therapy, or you could reduce head trauma, toxin exposure, infections,” says Fossel. “Those approaches are upstream. But what’s happening in between? We know genetic risk factors exist. We know amyloid and tau appear. But why?”
Solving biological discordance
Always fond of an analogy, Fossel likens the various approaches to aging as the parts of an orchestra playing a symphony.
“Imagine the symphony once played beautifully – now it’s discordant,” he says. “One group says the first violin is out of tune. Replace the violinist. Another group says the brass section is the problem.”
“Yamanaka-factor researchers say the strings are the issue. But I would argue they’re not asking deeply enough. Why did methylation change? Why did Yamanaka factor expression change? Why did amyloid accumulate? The real question is: what’s the optimal point of intervention – clinically and financially?”
Similarly, for the past 30 years, Fossel has argued that it has to do with altering telomere length.
“But theory alone isn’t enough, you must take it into human trials,” he says. “Until then, it’s still just theory. After that, we’ll see.”
“From my standpoint, many approaches are aiming at the wrong part of the symphony. They’re adjusting the string section – or even just the first violinist – when what we really need to change is the score and the conductor.”
It’s not lost on Fossel that Telocyte itself is initially focusing on a single indication, Alzheimer’s, in its development roadmap.
“If the FDA said aging was a disease, we’d target it directly – since they don’t, we target Alzheimer’s disease,” he says. “Strategically it makes sense: Everyone agrees it’s a disease. It’s fatal. Over 3,000 interventional trials have been registered – and essentially all have failed. Even the newest antibodies at best slow progression slightly in some patients. They don’t stop or cure the disease.”
“And the risk-benefit ratio strongly favors trying new approaches. If I offer you an experimental gene therapy for wrinkles, you’d say come back in ten years. If I offer you one for Alzheimer’s, the calculus changes.”
Critically, says Fossel, Telocyte is targeting cellular aging itself in its mission to combat Alzheimer’s, not amyloid or tau.
“The same principle could apply to coronary arteries, hepatocytes in the liver, podocytes in the kidney – any tissue,” he says. “The key issue is delivery. Viral vectors, for example, preferentially target certain cells. So the broader question remains: what cells can we effectively address?”
Ready for canine trials
While progress at Telocyte has slowed in recent years due to funding constraints, Fossel says that the company is now expecting the first tranche of funding from a group of unnamed investors and is preparing for “large animal trials” in dogs later this year.
“Two independent global groups have committed to fully funding the trials through the FDA process,” he says. “If funding timing works out, we’d like to use aging beagles and examine not just CNS function but multiple systems: coronary arteries, cardiac myocytes, kidney podocytes, lung pneumocytes and joint chondrocytes, along with the usual toxicology and physiological data.”
“Our first FDA submission would likely focus on the brain, but if funding permits, we would simultaneously present cardiovascular data as well. We want to collect everything at once so we don’t have to repeat large animal studies later.”
Fossel closes on a broader ethical point, highlighting a story about the famed American anthropologist Margaret Mead.
“She was asked what the first sign of civilization was, and her answer was a healed femur,” he says. “Why? Because a healed femur means someone cared for that person for months while they recovered: that’s civilization.”
“Today we tend to assume people simply grow old and fall apart. My view is that we should do better than that. We should be able to heal the femur.”
