26th May 2024

First generation of anti-aging treatments may arrive before 2040

Daniel Ives, PhD, an aging researcher from Cambridge University, predicts an optimistic timeline for the first effective anti‑aging therapies.

The ability to halt or even reverse the aging process must surely rank among the most exciting and consequential of scientific breakthroughs predicted to occur in the future. Partial reversals have already been achieved in worms, fruit flies, mice, and primates. If replicated in humans, profound implications can be expected for society, culture, and the economy.

In addition to massively eroding the burden of age-related health costs – a benefit likely amounting to many trillions of dollars – people's entire outlook on life may begin to shift, from short-term to longer-term interests. Knowing you have the option to live beyond a natural lifespan could fundamentally alter personal, financial, and other planning for generations to come.

For the more adventurous and dedicated, repeated treatments every few years could serve as a form of biological time travel, allowing those born in the 20th or early 21st centuries to experience the wonders of the far future.

In a recent interview with London Futurists, longevity researcher Daniel Ives, from the UK's University of Cambridge, discussed the latest progress in the field and presented a future roadmap to these world-altering therapies.

Mr. Ives, a co-founder of Shift Bioscience, began by explaining what inspired him to enter the field. He cited a TED Talk by Aubrey de Grey, a gerontologist who is known for running the SENS Research Foundation and has predicted that the first human to reach 1,000 years of age may already have been born.

Mr. Ives then explained to David Wood, interview co-host, that rejuvenation therapies may have additional benefits, beyond simply living longer. They could make long-duration space travel a lot safer, for example, by repairing damage to the human body caused by radiation and microgravity.

Epigenetics

As the interview progressed, Ives and Wood moved onto epigenetics, the core subject of their discussion. Epigenetics is a way to study how the covering or "packaging" of DNA in cells changes over time. This can alter which genes are turned on or off, while the underlying DNA sequence remains intact. It can include mechanisms like DNA methylation and histone modification, which have increasingly damaging consequences, the older we get. Understanding and manipulating these processes holds the potential for revolutionary anti-aging therapies.

The epigenetic clock, developed at the University of California in 2013, measures biological age by tracking DNA methylation levels. Essentially, this tool provides a more accurate estimate of an organism's age compared to chronological age. For example, two people may both have a chronological age of 40, while differing in their epigenetic clocks. A healthier person might have an epigenetic clock of only 37 or 38, but a less healthy person may show 42 or 43.

Ives highlighted that the ability to "reset" this epigenetic clock could extend the healthy lifespan of cells, thereby rejuvenating tissues and potentially reversing aspects of aging. In particular, he mentioned research into the Yamanaka factors. These are a set of four transcription factors – proteins that help turn specific genes "on" or "off" by binding to nearby DNA – capable of reprogramming adult cells back to a youthful, pluripotent state. While this technique is still in the experimental stage, it holds tremendous promise. Ives and his team at Shift Bioscience are refining these techniques to make them safer and more effective for potential clinical use.

P53, an example of a transcription factor, surrounding a piece of DNA. The P53 protects against cancer. Credit: Volodymyr Dvornyk/Dreamstime

Similar to the risks posed by telomeres – which are now known to play a crucial role in aging – Yamanaka factors are a double-edged sword. Unless they are carefully controlled, they can trigger cancer. The process of reprogramming cells to a youthful state involves significant changes in gene expression, which can lead to uncontrolled cell growth and tumour formation if the factors are not precisely regulated.

In addition to the Yamanaka factors, Ives and his team are researching alternative factors that may confer similar or even greater benefits. Shift Bioscience is just one of many companies in the longevity field who are exploring these alternatives.

"The writing's on the wall," said Ives. "We have something by the tail, but it's not perfect. Let's find an improved combination of factors that can reverse the age of cells without causing all of these major problems. This seems like the obvious thing to do, so we're trying to find this alternative set of factors."

Although scientists have now identified this key target for anti-aging therapies, the number of experiments needed is enormous. When considering all the available transcription factors, there are an estimated 365 million possible combinations. Ives highlighted the magnitude of this challenge by comparing it to his team's original plan of conducting about 35,000 experiments over two years in the wet lab, underscoring the exponential increase in scale required.

Deep learning

And now for the really good news. In 2023, scientists began using transformer models (a type of deep learning AI) and graph neural networks to understand the relationships between genes in real cells in the wet lab. They are now able to create virtual versions of these interactions that correlate well with real-world cells.

Using this new method, which is based on a model called single-cell GPT (scGPT), identifying the best combination of transcription factors could be made around 300 times faster. This would enable 10 million experiments within two years. That still isn't close to 365 million, but would "allow us to explore this vast landscape of different combinations of genes," identify the most useful areas on the landscape, and then "iterate on those things that are working," said Ives.

"I think the real-world version just isn't viable," he added, given the sheer numbers and timescale required. So-called longevity escape velocity is therefore likely to be achieved through algorithms, rather than purely physical experiments.

When asked by interviewer David Wood how this deep learning approach may play out, Ives predicted that a suitable combination of genes will be identified within the next two to three years, with safety confirmed in multiple cell types across the body. Initially, this would be demonstrated in mice, and possibly also non‑human primates, taking another two to three years. He expects human clinical trials to span nine or so years, divided into the usual phases I, II, and III.

This timeline of around 15 years – from the number-crunching work of the AI through to regulatory approval – could mean the first generation of anti-aging treatments emerging in the late 2030s. As different therapies are subsequently developed for different parts of the body, Ives said he believes that some biohackers like billionaire entrepreneur Bryan Johnson may be willing to experiment on themselves and combine multiple treatments, perhaps even all of those available at the time. This could pose risks, as the nascent technology is still being refined and its long-term effects are not yet fully understood.

"These therapies won't be perfect," acknowledged Mr. Ives. "Nothing is. When you try and solve a problem, it's never a perfect solution. But it's still a pretty big step forward."

For the ultimate goal of whole-body rejuvenation, he proposes the eventual need for a "cell replacement component" that would involve "a blueprinted genome from the outside, which is artificially held, like in a lab. You grow cells on the back of that, and then you replace tissue with blueprinted genomes when the cancer risk becomes too high."

"This is fascinating," said interview co-host David Wood. "The possibility is that, as a result of the epigenetic reversals which you're pioneering, amongst others, this will give people hope. They will see that a significant part of aging can be reversed, and this can arouse attention, and more resources will come piling into the field to address the remaining aspects of damage of aging. So, it will no longer just be a minor industry – it'll be something huge, maybe the largest industry in the world, with the largest public activist community behind it."

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