Why the key to slowing down ageing is targeting ‘zombie' cells

Telegraph

08-05-2025

At last year's British Society for Research on Ageing conference, an annual meeting to discuss the latest ideas for improving healthy ageing and lifespan, one theme kept cropping up – how best to rid the body of senescent cells?
Often dubbed 'zombie cells,' because instead of replicating and then dying off like most healthy cells in our body, senescent cells stop dividing and instead simply linger, refusing to disappear. They were first discovered in the 1960s but have attracted growing attention in the past two decades, because their steady accumulation throughout our lives is increasingly being implicated in almost all age-related diseases and even the underlying ageing process itself.
'They've been described as the undead cells, and they seem to be a common denominator in almost every single major age associated disease that has been ever looked at,' says Dr Johannes Grillari, the director of the Ludwig Boltzmann Institute for Traumatology in Vienna, who studies senescent cells. 'You see this whether it's cardiovascular diseases, neurodegenerative diseases, musculoskeletal diseases, lung fibrosis, chronic kidney disease. Name any one of these killers, and senescent cells are there.'
The flip side of this, of course, is that by removing them, we might actually have a new means of curing many diseases, and perhaps even slowing the underlying ageing process. Because of this, research into senolytics – drugs capable of removing senescent cells – is now one of the active areas of longevity science, with dozens of clinical trials underway around the world.
So what causes these zombie cells to form, can we stop them, and what do we know about future drugs?
What are senescent cells?
At the Mayo Clinic in Rochester, Minnesota, the geriatrician and medical professor James Kirkland is one of the world's leading experts on senescent cells. He explains that while excessive numbers can harm us, our body has evolved to harbour these cells for a number of reasons – they're involved in everything from childbirth to wound healing.
'It's actually molecules produced by senescent cells that appear to drive the baby through the birth canal in the last five days of pregnancy,' he says.
Likewise, the formation of these zombie cells also acts as one of the body's inbuilt protective mechanisms against cancer development. Over our lifetimes, this prevents numerous individual cancer cells from continuing to grow and form a tumour. 'Senescence means that cells carrying cancerous mutations in their DNA then stop dividing, preventing them from developing into a rapidly growing cancer,' says Prof Kirkland.
However, the problem is that as we age, we gradually accumulate more and more senescent cells. While they no longer divide, they are still metabolically active, which means they're still able to communicate with surrounding cells by producing continuous streams of molecules. In particular, some zombie cells start to generate large quantities of pro-inflammatory cytokines – proteins which are associated with chronic inflammation.
'By the time we reach old age, we have senescent cells in many of our tissues, creating this chronic low-grade inflammation,' says Dr Grillari. 'We think that's their most detrimental activity.'
How they affect the body
While we can accumulate zombie cells in every single one of our organs, there are some where they have been particularly implicated in disease.
Spine and joints
Zombie cells building up in spinal discs – cushion-like structures that sit between the vertebrae – either as a result of ageing or damage, have been associated with back pain. The same is true for the knees and ankles where growing numbers of zombie cells in the cartilage and soft tissues which line the inner surface of our joints, cause inflammation and loss of flexibility. This has been linked to osteoarthritis, the degenerative joint disease which represents the most common form of arthritis.
Liver, pancreas, gut and fat tissue
At Amsterdam University Medical Centre, the gastroenterologist Dr Stijn Meijnikman has been studying the role of zombie cells in common metabolic diseases, from Type 2 diabetes to non-alcoholic fatty liver disease. According to Dr Meijnikman, the development of these diseases is linked to zombie cells accumulating in many of the internal organs, as well as the gut and even fat tissue. Because these cells are no longer working as they should, this leads to loss of organ function and the formation of scar tissue.
'In all metabolic diseases, we can see these senescent cells popping up everywhere,' he says.
Kidneys
Studies have previously linked zombie cells to kidney and other organ transplant failures, one of the reasons why organs donated by people over the age of 60 make for less successful transplant candidates. 'There's been papers that have shown that the more senescent cells you have in a transplant organ, the worse the outcome of the transplantation,' says Dr Grillari.
Eyes
Our ability to see owes much to lens epithelial cells, those which are responsible for the growth and development of the eye lens. However, with age or damage – for example from excessive exposure to UV light, as a result of not wearing sunglasses - these cells can become senescent, leading to the eventual formation of cataracts.
Brain
In 2022, a study from American researchers backed by the US National Institute on Ageing found that patients with Alzheimer's disease have considerably more zombie cells in their brains than those who are cognitively normal. The research suggested senescence could contribute to the build-up of toxic tau tangles in the brain which represent one of the hallmarks of the disease.
Senescent cells and ageing
So what makes us more vulnerable to accumulating senescent cells, and is there anything we can do to protect ourselves?
Three years ago, a study from the Mayo Clinic indicated that physical inactivity is a major cause of prematurely accumulating large numbers of zombie cells, while on the other hand, regular moderate-vigorous activity may help by kicking the immune system into gear and provoking it to clear these cells.
One study of 170 healthy participants aged between 18 and 80 found that doing more than 240 minutes a month of any form of moderate physical activity (for example running, swimming, and cycling) leads to fewer zombie cells. Resistance training using weights or press-ups may also help, with one study of overweight and obese women in their 70s, finding that five months of resistance training resulted in fewer zombie cells in their fat tissue.
At the same time, the relationship between exercise and senescence is not straightforward. Some studies have indicated that forms of exercise where the body is pushed to extreme exhaustion, for example ultra-marathon running or attempting endurance challenges without sufficient training, could push you to accumulate more of these cells.
Last year, another study suggested that adequate levels of sleep, intermittent fasting, consuming enough dietary fibre and commonly available probiotics, such as Lactobacillus, may help reduce your levels of zombie cells. On the other hand, regularly consuming excess alcohol, smoking, exposure to sunlight without sufficient protection and chronic stress drives the formation of these cells.
Can you get rid of senescent cells?
But for people who have already accumulated large numbers of zombie cells which are contributing to different diseases, the main hope is future drug treatments which can rid these cells from the body, an emerging class of medicines known as senolytics.
Over the last decade, Prof Kirkland has pioneered studies on a series of compounds, which include the chemotherapy drug dasatinib and high doses of two natural plant chemicals quercetin and fisetin, originally found in various fruits and vegetables. His work, and that of others, has shown that they can help eliminate zombie cells by disabling the biological pathways which allow them to persist, causing them to self-destruct.
Dr Katarzyna Whysall, an associate professor at the University of Galway, describes these three senolytics as already showing great promise in tackling various age-related disorders. One human trial, carried out by Prof Kirkland in patients with a form of chronic lung disease, found that three weeks of treatment with dasatinib and quercetin improved their physical strength in various ways.
'Another small study found encouraging results for senolytics use in Alzheimer's disease, although more research is still needed,' she says.
Other senolytics are also currently being researched. A recently published study from Canadian scientists found that two drug candidates, called o-vanillin and RG-7112, demonstrated the ability to clear zombie cells from spinal discs in mice, suggesting that they could potentially represent a future treatment for back pain.
But at the moment, the most well-characterised senolytics are dasatinib and quercetin and this treatment combination is currently being investigated in several more human trials ranging from early Alzheimer's disease to chronic kidney disease. Dr Meijnikman is currently leading a Dutch government-funded trial investigating the potential of these drugs to reverse non-alcoholic fatty liver disease.
'Based on studies in mice, if you can clear the senescent cells from the liver, you get rid of the fibrosis [a medical term for scarring],' says Dr Meijnikman. 'Of course, humans are different which is why we're doing this proof-of-concept trial for 21 weeks with a liver biopsy before and after. If we can see a decrease in fibrosis in this very short-term trial, that would create an incentive for longer trials with more patients.'
At the same time, Dr Meijnikman is keen to emphasise that people should not try taking these drugs at home, and we're still far from a point where they can be given to healthy mid-lifers to see if they can help slow ageing. For example, one very real risk of clearing too many zombie cells with senolytics drugs which needs to be assessed in these trials is that this could make people more vulnerable to developing cancers.
'This is why at the moment they're only being given in clinical settings to people who already have severe disease, who could benefit from them,' he says. 'With our trial, we're trying to do a 'hit and run' approach where just for a few weeks, we temporarily disrupt these pathways which are allowing senescent cells to survive, enough to clear them but hopefully without risking longer term side effects.'