A single dose of stem cells can significantly improve the physical endurance of older people living with frailty, a condition that affects 1 in 10 people over the age of 65, according to new research published in the journal Cell Stem Cell.
The randomised, placebo-controlled trial tested four escalating doses of laromestrocel – a therapy derived from donated bone marrow – in 148 adults aged between 70 and 85, all of whom had been formally diagnosed with frailty.
After nine months, those who received the highest dose walked an average of 60 metres further in a standard six-minute walk test than participants who had received a placebo. That’s an improvement of around 20 per cent.
"The results were kind of stunning," Dr Joshua Hare, chief science officer of Longeveron, the company developing the therapy, told BBC Science Focus. “There was this beautiful separation based on time and based on dose. The more we gave, the more the increase there was in the six-minute walk test.”
Frailty is a common medical condition, though one that remains widely misunderstood. It describes a state of heightened vulnerability to stressors – infections, falls, surgery – that goes well beyond what would be expected from normal ageing.
Its hallmarks include diminished muscle strength, reduced endurance, and a sharply increased risk of disability, hospitalisation, and death. According to the British Geriatric Society, someone with severe frailty is five times more likely to die within a year than someone without it.
"If you look at 80-year-olds, some of them will be in a nursing home requiring continuous 24-hour care, and some are still out there playing tennis and golf and living a full life,” Hare said. “What's the difference? It turns out there's something biological happening."
That biology, Hare argues, centres on inflammation – or "inflammageing”, as he calls it, given its age-related component. As people get older, the immune system becomes dysregulated, producing elevated levels of inflammatory signalling molecules called cytokines.
This persistent inflammation damages blood vessels, depletes stem cell reserves, and accelerates the loss of muscle mass, a process known as sarcopenia.
The result is frailty: a body increasingly unable to repair itself or respond effectively to physical or medical stress.
Current treatments amount to little more than nutritional support and physical therapy programmes.
"What we typically do with people like this is not much," Hare said. "So we said, ‘Look, we’ve got to see if we can tackle this at a biological level.’ We know what the problem is.”
Mesenchymal stem cells, which are found naturally in bone marrow and other tissues, have attracted scientific interest for their ability to modulate the immune system.
Crucially, they carry few of the surface proteins that would ordinarily trigger an immune rejection, meaning recipients do not need to take the immunosuppressive medications that can leave already-vulnerable patients at risk of fatal infections.
Hare and his colleagues collected stem cells from donated bone marrow and administered them intravenously.
Participants received either a placebo or one of four doses of laromestrocel. Neither the patients nor the clinicians administering the treatment knew which they had received.
The results, tracked every three months over nine months, were clear: greater amounts of stem cells produced greater improvements in walking distance. In the placebo group, meanwhile, physical performance declined by the end, as would be expected in a population of frail 75-year-olds left untreated.
Patient-reported outcomes – questionnaires asking participants to assess their own physical performance, upper body strength, and mobility – showed improvements that correlated with the gains measured in the walk test. Participants also improved on a physician-assessed frailty scale, which runs from one (least frail) to nine (most frail).
“Fully one-third of the people who got treated reverted to a two or a three on the scale, which are healthy scores,” Hare said. “A two or three means you don’t have frailty anymore.”
The researchers also identified a potential biological marker of the treatment's effect: soluble Tie2, a protein shed into the bloodstream when blood vessel walls are inflamed or degraded. In patients who received stem cells, levels of this marker fell in line with the dosage.
“This is some of the best evidence yet that we can use a medical treatment to reverse frailty,” Dr Andrew Steele, director of The Longevity Initiative, told BBC Science Focus. “We’ve known for a long time that exercise can help, but that’s often challenging, especially in the very frail, so it’s incredible to be able to not just slow the decline but show actual improvements with an infusion of stem cells.” Steele was not involved in the research.
Yet the study raises questions that remain unanswered. How the therapy works is still not entirely clear since the stem cells have wide-ranging effects.
“It might be that these cells go to parts of the body where they’re needed and build new cells,” Steele said. “Or it might just be that they emit a helpful anti-ageing cocktail of molecules that encourages the body’s own cells to rejuvenate.”
The trial also followed participants for nine months only, leaving open the question of whether improvements persist long-term or how effective repeat doses might be.
Hare said his team has conducted some longer-term tests, in which participants receive multiple doses. The preliminary picture is encouraging, with people appearing to improve and then sustain their gains with no adverse side effects, but without a placebo group, the evidence is less solid than the randomised trial. Formal studies of repeat dosing are being planned.
The path to widespread clinical use also faces a significant regulatory obstacle. Neither the US Food and Drug Administration nor its European counterparts currently recognise frailty as a disease, which complicates the approval process considerably.
"It's going to be a battle," Hare said, stating that an approval pathway may prove easier for Alzheimer's disease, where laromestrocel has already shown promising results in a separate trial.
"We think it'll be approved for Alzheimer's disease before it's approved for ageing frailty, because that's a clearly defined disease with an unmet need."
For now, the trial represents something promising: robust, placebo-controlled evidence that frailty is not simply an inevitable feature of getting old, but a biological process that can, at least in part, be reversed.
"Human lifespan has almost doubled in the last 120 years," Hare said. "But even though longevity is increasing, health span isn't keeping up with it. There's always this period of time at the end of life where people have disability, infirmity, require support and lose function.”
If progress continues, that gap could finally begin to close.
Read more:
- This new drug may have cracked the 'cheat code' for reversing ageing
- 10 breakthroughs that could soon slow or reverse your biological age
- New study reveals the best walking pace for a long, healthy life
