In 1961, Leonard Hayflick discovered that human cells grown in a laboratory stop dividing after roughly fifty divisions. They do not die right away, though. They linger, release inflammatory substances and poison their neighbours. Sixty years on, biologists have named them zombie cells and linked them to almost every disease of old age, from arthritis to Alzheimer’s. Find out what we know about senescent cells and what can actually be done about them.

Key facts about senescent cells:

What senescent cells are – cells that have permanently stopped dividing but have not died, and which release inflammatory substances into their surroundings.
SASP – the senescence-associated secretory phenotype, a cocktail of cytokines and enzymes that zombie cells use to damage neighbouring tissue.
Removing them in mice extended their healthy lifespan by up to 25 per cent, yet human evidence remains preliminary.
Senolytics are compounds that clear senescent cells – some are in clinical trials, others occur naturally in food.
Lifestyle – exercise, intermittent fasting, cutting back on sugar and avoiding sleep under seven hours slow down the formation of zombie cells.

What are senescent cells?

Senescent cells are cells that have permanently left the division cycle, yet remain alive and metabolically active. They typically appear in response to DNA damage, shortened telomeres (the caps on chromosomes that protect DNA) or excessive oxidative stress. In a young body, the immune system spots them and clears them within days. With age, the clean-up falters and senescent cells start to accumulate in tissues, from the skin to the liver and heart muscle.

Their role is ambiguous. In the short term, they protect against cancer – a cell with damaged DNA that stops dividing will not pass the error on. This mechanism is part of the hallmarks of ageing and one of the reasons evolution has preserved it at all. In the long term, the same cells become a source of chronic inflammation, which is one of the core mechanisms of ageing biology.

What is SASP and how does it affect neighbouring cells?

SASP, the senescence-associated secretory phenotype, is the set of substances that senescent cells pour into their surroundings. It contains pro-inflammatory cytokines (IL-6, IL-8), enzymes that digest connective tissue and growth factors that confuse neighbouring cells. Readers often ask what zombie cells really are – these are exactly that: aged cells that have not died and instead leak SASP into surrounding tissues. In practice, a single zombie cell can push healthy cells towards senescence, creating a cascade. This is how local hotspots of ageing develop – in the skin, joint cartilage and blood vessels.

Does removing zombie cells extend life?

In mice – yes; in humans – we do not know yet. In 2016, a team at the Mayo Clinic showed that genetically removing senescent cells in mice extended their median lifespan by 17 to 35 per cent, depending on the strain. The animals were fitter, had healthier kidneys and hearts, and developed cancer less often. The catch is that the genetic trick used in that study does not exist in humans.

Human data are far more cautious. In a 2019 pilot trial, patients with idiopathic pulmonary fibrosis received a three-day course of experimental senolytics and their physical performance improved within a week. The trial, however, included only fourteen people, ran for just a few weeks and did not measure lifespan. A robust answer on whether senolytics extend human life must wait for large, multi-year studies – currently in phase II and III.

What are senolytics and how do they work?

Many people ask what senolytics actually are. The answer is simple: senolytics are compounds that selectively kill senescent cells and leave healthy ones alone. Zombie cells stay alive thanks to over-active anti-apoptotic pathways – in plain terms, they have reinforced defences against self-destruction. Senolytics block those pathways, the senescent cell undergoes programmed death and macrophages sweep up the remains.

Main groups of senolytics studied scientifically:

The experimental D+Q duo – a combination of an anti-cancer drug with quercetin, tested in small clinical trials in patients with pulmonary fibrosis and diabetes.
Fisetin – a flavonoid found in strawberries, currently in clinical trials in people over the age of 65.
Experimental prescription compounds – block the proteins that protect senescent cells from self-destruction; effective in the lab but toxic to human platelets.
Natural polyphenols – fisetin and quercetin, weaker than pharmaceutical senolytics but easier to obtain through diet.

None of these compounds is a registered anti-ageing medicine today. Research is ongoing, results are promising but preliminary. For now, senolytics belong to science, not to the pharmacy.

Can natural senolytics from the diet help?

Natural senolytics from the diet work far more weakly than compounds tested in clinics, yet they can support the process of clearing zombie cells. The main players are flavonoids – polyphenols found in fruit and vegetables, which in a test tube can trigger the death of senescent cells. The best-studied are quercetin and fisetin. Their advantage is simple: they are safe within a normal diet and require no prescription.

Where can you get quercetin from the diet?

Quercetin is present in onions, capers, apples, broccoli, black tea and red wine. The richest source is capers – around 180 milligrams per 100 grams, although few people eat large portions. In practice, ordinary onions and apples eaten with the skin supply most of the daily intake. Boiling in water reduces quercetin content by 30 to 75 per cent, so flavonoid-rich vegetables are best eaten raw, baked or braised.

What is fisetin and what is the evidence?

Fisetin is a flavonoid found mainly in strawberries, with smaller amounts in apples, persimmons and onions. In 2018, a Mayo Clinic team led by Paul Robbins showed that short courses of fisetin extended the lifespan of older mice by up to 10 per cent and improved inflammatory markers. In humans, several clinical trials are underway, with the first results expected over the next few years. For the time being, fisetin remains a dietary compound with a good safety profile but without official dosing recommendations.

Why aren’t senolytics a medicine yet?

Because the journey from a promising compound in a test tube to a registered medicine takes fifteen years and costs billions of pounds. Senolytics do perform beautifully in mice and cell lines, yet the human body is far more complex. We still do not know what dose is safe, how often it should be given or at what age to start. A handful of small clinical trials is not enough to put a drug on the shelves.

Key barriers to the development of senolytics:

Lack of reliable biomarkers – we cannot easily measure how many senescent cells a given person has before and after therapy.
Heterogeneity of zombie cells – senescent cells in the liver behave differently from those in the brain, and a single drug rarely works on all of them.
Risk of side effects – some senolytics damage platelets or strain the liver, which rules out long-term use.
Long research horizons – checking the effect on human lifespan requires decades of follow-up, not months.
Patient selection – senolytics may help people of a specific age or with a particular condition, and do nothing for others.

Phase II and III trials started only a few years ago, and a realistic date for the first registration is the second half of the 2020s at the earliest. Until then, the only sensible strategy is a lifestyle that shapes the formation of senescent cells.

How can lifestyle reduce the number of senescent cells?

The most effective approach combines movement, sensible eating and regular sleep. Regular physical activity switches on autophagy – the mechanism by which cells clean up damaged components inside themselves. This process is explained in daily cellular repair. Calorie restriction, intermittent fasting and lower insulin levels further reduce the signals that push cells towards senescence.

The second pillar is managing DNA damage. A senescent cell is often a cell that tried to fix too many lesions and finally gave up. Anything that lowers oxidative stress therefore indirectly slows down the creation of zombie cells. A diet rich in polyphenols, avoiding tobacco and heavy drinking, and protecting the skin from UV radiation achieve more than many experimental supplements.

Which habits accelerate senescence?

Four factors accelerate senescence the most: smoking, chronic sleep deprivation, a high-calorie diet based on ultra-processed foods and chronic stress. Tobacco directly damages DNA in lung and blood vessel cells. Short sleep (under six hours) limits nightly repair and telomerase activity. A diet rich in simple sugars keeps insulin elevated, which in turn activates pathways that encourage senescence.

What slows it down?

What slows it down is anything that reduces cellular damage and supports ongoing repair in the background. We are talking about concrete, repeatable habits, not miracle cures. Dietary amounts are safe, but before supplementing with fisetin, high-dose quercetin or compounds marketed as senolytic serums or senolytic cosmetics, it is worth speaking to a doctor – particularly when taking blood thinners.

Habits that slow senescence:

Strength training two to three times a week – stimulates mitochondria and autophagy in muscles, limiting the formation of zombie cells in muscle tissue.
Seven to eight hours of sleep – the window during which the body repairs DNA and clears damaged proteins.
A Mediterranean diet – olive oil, fish, pulses and colourful vegetables supply polyphenols and omega-3 fatty acids that dampen inflammation.
Eating windows and fasting – a 12 to 14 hour gap between dinner and breakfast supports autophagy without calorie restriction.
Stress management – breathing techniques, outdoor walks and regular social contact lower cortisol, which accelerates cellular ageing.

This approach will not replace senolytics in a laboratory, but it has two advantages: it works today and does not carry the risk of an unapproved therapy.

FAQ: Frequently asked questions about senescent cells

What are zombie cells?

Zombie cells are the informal name for senescent cells, which have permanently stopped dividing yet are still alive and release inflammatory substances that damage neighbouring tissue.

Can senescent cells be removed?

Removing senescent cells is possible in the laboratory and in animals, while clinical trials on effective and safe senolytics in humans are still underway.

What are senolytics and can they be bought?

Senolytics are compounds that selectively clear senescent cells – some of them are in clinical trials, and none has yet been registered as an anti-ageing medicine.

How can senescent cells be reduced naturally?

Regular exercise, seven to eight hours of sleep, a Mediterranean diet, intermittent fasting and reducing sugar slow the formation of zombie cells and support their clearance by the immune system.

References:

Baker, D. J., et al. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature. https://doi.org/10.1038/nature16932
Justice, J. N., et al. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. https://doi.org/10.1016/j.ebiom.2018.12.052
Yousefzadeh, M. J., et al. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. https://doi.org/10.1016/j.ebiom.2018.09.015

Zombie cells – what senescent cells are and how to remove them