About a decade ago, 125 amateur cyclists from all over the UK filed into the laboratories at King’s College London. Aged between 55 and 79, they were there to participate in a long-term study examining how regular physical activity affects the ageing process.
Janet Lord, professor of immune cell biology at Birmingham University, who conducted the study in collaboration with King’s professor Steve Harridge, said the team were surprised by some findings when they examined the cyclists’ bodies and took blood samples over several years.
Her subjects, described as “very keen cyclists”, were fairly fit, riding up to 60 miles a week.
“We found things like increased fat in the body, which a lot of people tell you ‘oh, there’s nothing you can do about that, that’s part of ageing’ – just were not true. They didn’t happen in this group. We compared them with healthy older adults who were not regular exercisers. Our group did not lose muscle … and didn’t lose much bone mass either,” said Lord, who is the director of the university’s Institute for Inflammation and Ageing, and a special adviser to the House of Lords inquiry into ageing, which published a report in 2021.
The biggest surprise related to the thymus gland, which sits on top of the heart and makes white blood cells called T-cells. It normally shrinks in older people – but not in the cyclists. Its decline affects people’s immune system. “And that’s why you’re not very good at responding to new infections like Covid, or vaccines,” Lord said.
She and her team are still monitoring the cyclists to figure out how much exercise is needed, and how intense it needs to be, to reap the health benefits.
The study is one of many projects undertaken at British universities in recent years, as the UK carves out a leading role in ageing research globally. While still in its infancy, the longevity science sector is set to become a multibillion-dollar industry, forecast to grow to $2bn (£1.6bn) by 2030, according to Insight Analytics.
A number of longevity biotech startups have sprung up, such as Senisca in Exeter, Genflow Biosciences in London, and Shift Bioscience and clock.bio in Cambridge. In the US, the pack is led by California firms such as Altos Labs, which also has a research institute in Cambridge, Calico, backed by Google’s owner Alphabet, Unity Biotechnology and Retro Biosciences.
“We punch way above our weight in terms of the quality and the quantity of our scientific output in the ageing space,” said Lorna Harries, professor of molecular genetics at the University of Exeter, who set up the spinout Senisca in 2020. “But while we’re a scientific powerhouse, we need to develop our ability to turn our findings into things that are tangible outcomes in the real world.”
What many of these firms are working towards is a recipe for helping us live longer by ensuring our cells stay healthy. Currently, girls born in the UK in 2020 are expected to live for about 90 years, while boys are predicted to live about 87 years.
“Potentially, you could live to 120 if you did all the right things and you were lucky enough to have the right genes,” said Prof Lynne Cox at the University of Oxford, who specialises in cell senescence – the way cells that have been damaged or stressed change to a state that can damage surrounding tissues.
Ageing is generally regarded as the accumulation of damage to cells, or wear and tear, over time, that can lead to loss of function and common diseases such as diabetes, heart disease, dementia and cancer.
More than 60 years ago, the American anatomist Leonard Hayflick discovered that human cells have limited capacity to divide, after which they become senescent.
In 1993, Cynthia Kenyon at the University of California at San Francisco conducted a pioneering study which demonstrated that mutations in one gene in a species of worm could double their lifespan. But this could not be reproduced in humans. Today, there are various attempts at cellular reprogramming or other tweaks to halt or reverse ageing.
London-listed Genflow Biosciences, which last December became the first longevity company to float in Europe, uses a gene variant found in centenarians to try to develop a therapy that can repair DNA damage and extend the time we stay in good health by 25%. It intends to test an experimental therapy on people with an age-related liver disease called NASH within 18 months.
“Some people are lucky to have the good gene, and what we want to do is share that luck with everybody,” said Eric Leire, Genflow’s founder. “So it’s not just a few people who will have the chance to even live to 120 and never see chemotherapy in their life.”
Senisca is working on ways to restore the ability of cells to fine-tune the expression of their genes, in order to rejuvenate aged cells.
“Our fundamental discovery dates back almost 15 years,” said Harries. “Each gene can make several different messages that contain instructions depending on what the cell encounters in its environment. We discovered that as we age, our cells lose this ability, which means they cannot react to challenging signals from the environment and they become senescent.”
She added: “We have found that if we restore the activity of those genes, we can restore the ability of the cell to make what it needs, which allows the cells to rejuvenate.” Senisca aims to develop therapies that can benefit older people within the next 10 years.
Shift Bioscience, co-founded by the former Cambridge University biologist Daniel Ives, uses machine learning to explore cellular reprogramming.
The German-American geneticist Steve Horvath pioneered the first accurate “clock” to determine human ageing by examining chemical changes to DNA in different tissues. Similarly, Shift has developed a single cell ageing clock and will use it to find safe combinations of genes for cellular reprogramming. This is expected to take two years, followed by testing in human cells in the lab, on mice and eventually in humans.
Ives’s father, Steve, who is Shift’s finance chief, said: “The idea is to introduce genes into cells to trigger processes which make those cells biologically younger. This new focus on reprogramming really represents a new paradigm targeting the root causes of ageing.”
The co-founder of clock.bio, Mark Kotter, and its chief executive, Markus Gstöttner, plan to start a clinical trial before 2030 that aims to rejuvenate cells.
The anti-ageing industry in the US has attracted a flurry of interest from a clutch of health-obsessed tech entrepreneurs, some of whom are known as “buff billionaires” for their newfound fitness. Among those is Amazon founder Jeff Bezos, who backs Altos Labs.
Bezos and PayPal founder Peter Thiel are investors in San Francisco-based Unity Biotechnology, which focuses on eliminating or modulating senescent cells to restore damaged tissues, initially for neurological conditions and eye diseases. The artificial intelligence entrepreneur Sam Altman, chief executive of OpenAI, has invested in Retro Biosciences, which is betting on cellular reprogramming, as is NewLimit, backed by the cryptocurrency billionaire Brian Armstrong, chief executive of Coinbase.
“In the UK, there are way fewer startups in this space than you would expect, based on how much research we do,” said Harries. “I suspect it’s because as academics in the UK, we are not necessarily trained to be entrepreneurial.”
Cox says British academics often have too many other commitments. “The incentives are not there at the moment for academics to push to startups – it’s an incredibly risky thing to do … A lot of universities really struggle with the idea of commercialising.”
Lord points to the lack of a thriving venture capital sector to fund startups. “It’s huge in the US, and we just don’t have that here. So we’re very reliant on government funding. If we could get more venture capitalists interested in what’s going on in the UK, that would help.”
One area of research is inflammation, a main driver of biological ageing. Cox said: “The human genome is full of bits of viral DNA that crept in there over our evolution, and they’re normally repressed. But as we get older, they jump out again and trigger inflammation, the body’s response to an infection. The problem is the immune system is also old, and so it can’t deal with it.”
A group at Oxford University is looking at ways of improving elderly immune systems by making cells more able to clear out their rubbish, in a process called autophagy.
Centenarians tend to pass on longevity genes, but having the right gut bacteria is also key, academics say. Researchers in Japan found that gut bacteria in centenarians are different from those of other older people; one bacterium even acts as an antibiotic and kills harmful bacteria in the gut.
Social and economic factors come into play too. “People living with socioeconomic deprivation have a higher level of cell senescence; they’ve got more inflammation,” says Cox. “They’re exposed to things like pollution or poor diets. And you can see this molecular signature of them ageing faster.”
Researchers talk about a paradigm shift – moving to treating the shared causes of ageing diseases rather than their consequences, which will relieve the pressure on the NHS and other health systems.
Some are confident that the UK can be among the leaders in the longevity industry. Miles Witham, a professor of clinical trials for older people at Newcastle University, says: “We are world leaders in terms of laboratory ageing research in the UK; we’re also world leaders in the epidemiology of ageing in the UK. What is hard is to make sure that what we’ve learned comes through into clinical trials in humans and eventually into the clinic [to patients]. Nobody’s really doing enough of this in any country in the world. We’re trying to make sure that the UK is at the forefront of this.”
