Frailty sets in far earlier than you’d expect, but you can reverse it

If we live long enough, many of us will eventually start to exhibit telltale signs of frailty, from unsteady feet to mental confusion. Yet not all. Think of Julia Hawkins, who set world records in the 100-metre sprint after taking up running at age 100. Or the journalist Leonard Barden, who still files weekly chess columns at the age of 96. Such people defy the odds and seem to dodge the destiny of frailty. The question is: why?

The answer lies in new insights into frailty, which show that it is a far more complex and diverse condition than it first appears. Surprisingly, we are also discovering how it can start developing early in our life, with a significant number of people in their 30s or 40s unknowingly in a “pre-frail” state.

The good news is that we have more control over our future frailty than we might realise. Many of the factors that lead to it are modifiable, and midlife is a great time to take action. What’s more, this new understanding of how to age strongly is revealing unexpected ways to fight frailty – and it’s not all about exercise and weight training.

Becoming vulnerable

Roughly speaking, frailty affects around 10 per cent of people in their 50s, rising to around half of all those in their 80s. Although it is linked to ageing, it is also highly variable among people of the same chronological age.

Most of us are familiar with physical frailty, which includes the loss of muscle mass known as sarcopenia, which can make it difficult to get out of a chair without assistance, as well as osteoporosis, which leads to brittle bones and fractures. But people can also be cognitively frail, making them markedly more vulnerable to dementia. Overall, people who are frail have fewer biological reserves, so are much less resilient to any kind of trauma – whether that’s an infection, an operation or the sudden death of a family member – which leaves them prone to a significant decline in overall health.

“Frailty is more of a state of being than a specific disease,” says Mary Ni Lochlainn, a specialist in geriatric medicine at King’s College London. “It’s a state of reduced resilience, reduced reserve, so your ability to bounce back after a stressor is impaired.”

Frailty is increasingly being recognised as something that is important to spot as early as possible. Not only are older people with severe frailty five times more likely to die within the next year than those without, but frailty is linked to an increased risk of falls, delirium, hospital-acquired infections and dementia.

But frailty isn’t a sudden event. We now know that it represents the endpoint of a gradual continuum that can begin surprisingly early in life. One 2018 study of nearly half a million people in the UK found that 38 per cent of women aged 37 to 45 and 35 per cent of men had indicators of pre-frailty, a state that Tom Brennan, an ageing researcher at Flinders University in Australia, describes as “an early-warning stage”.

The pre-frailty stage

“Physiologically, pre-frailty reflects a body under strain, but still highly adaptable,” says Brennan. “People are not yet experiencing major limitations in everyday function, but small deficits are beginning to accumulate. They may feel more tired than they used to, move a little more slowly, be less active or notice subtle losses in strength.”

Identifying frailty has become a topic of increasing priority in medical practice. Since 2016, UK health services have been using a digital tool integrated into primary care electronic health record systems that enables doctors to predict older people’s risks of living with frailty, and intervene earlier. It is based on research carried out in the early 2000s by the geriatrician Kenneth Rockwood at Dalhousie University in Canada, who developed a way of assessing frailty as the combined accumulation of different physiological deficits, ranging from diseases to functional limitations.

Other ageing researchers have attempted to narrow down the main hallmarks of frailty. In a now landmark 2001 study, geriatrician Linda Fried, then at the Johns Hopkins Medical Institutions in Maryland, and her colleagues defined five traits as being particularly predictive of frailty: unintentional weight loss, self-reported exhaustion, low physical activity, slow walking speed and weak grip strength. If a person has one or two, they are pre-frail, but if they have three or more, they classify as frail.

“They worked out that this was a good predictor of future outcomes in terms of institutionalisation or vulnerability,” says Claire Steves, who studies ageing and health at King’s College London.

Of the five traits, Steves highlights walking speed as perhaps the most revealing of all. This is because walking utilises multiple bodily systems and can be affected by various underlying health conditions. Poor vascular health, for example, creates stiffness in the legs, as well as affecting the brain’s movement centres. “Walking is very much a whole-body thing,” says Steves. “In order to walk quickly, you need to have basic muscle function, really good balance, good spatial awareness of what’s around you and cognition to put all of that together.”

But why do some people begin to develop traits of frailty at a relatively young age, while others stay fit and robust well into their 90s? Understanding this requires a little dive into the underlying biology of ageing.

How the gut drives frailty

When I began researching my upcoming book The Age Code, which delves into the link between what we eat and how we age, I noted how frailty was associated with reduced diversity of the gut microbiome and a decrease in the number of health-promoting anti-inflammatory metabolites produced by these microbes, all of which results in heightened inflammation throughout the body. Much of this is due to the close connection between the state of the gut and the immune system.

As we age, we develop growing numbers of senescent cells – zombie-like cells that no longer divide and replicate, but simply linger and spew out a steady stream of inflammatory molecules. “When you get to the age of 70 or 75, you could have anything between 300 and 500 grams of senescent cells in your body,” says Nicholas Rattray at the University of Strathclyde in Glasgow, UK.

But while healthy midlifers and older adults do better at keeping senescent cells at bay, studies have shown that both pre-frailty and frailty are associated with the formation of growing numbers of senescent immune cells in the gut. This triggers intestinal inflammation, while blooms of harmful populations of gut bacteria can synthesise metabolites that make senescent cell formation more likely.

This all steadily worsens a person’s wider health. As white blood cells called T-cells become senescent, the immune system is less capable of fighting off infections, while the inflammatory molecules being generated in the gut can affect distant organ systems, from muscle tissue to the brain. The inflammation can also drive a phenomenon known as anabolic resistance in which the body struggles to generate new muscle tissue, even in response to protein intake and exercise, creating a heightened risk of sarcopenia.

“There’s a lot of direct evidence linking inflammation and loss of muscle mass,” says Niharika Duggal at the University of Birmingham, UK.

Other hallmarks of ageing are also involved in frailty – in particular, impairments to the powerhouses in our cells called mitochondria, which convert nutrients like fats and sugars into the molecule ATP that fuels the body. People who are frail display marked mitochondrial dysfunction. For instance, a 2019 study by Rattray and his colleagues of 1191 people aged between 56 and 84 identified 12 blood-based metabolites that differentiate the frail from the non-frail, pointing to an impaired ability to metabolise fats – which affects their brain, immune and wider organ health.

“Ultimately, all the cells in our body need energy to go about their daily business,” says Rattray. “As those mechanisms break down, your cells are going to have reduced capacity, and less ability to recover from insults.”

But there are some surprising causes of frailty too, such as your state of mind. Brennan has investigated behavioural and psychological changes in midlife that often precede visible physical decline. A study he did with colleagues last year found that, while someone might appear healthy, their psyche can act as an early red flag, with pre-frail individuals being more likely than non-frail people to feel lonely and hold more negative attitudes towards ageing.

These discoveries are already being used in healthcare settings. In France, for instance, the National Public Health Agency has prioritised identifying a person’s level of frailty as a way of preventing falls, with doctors being incentivised to assess older adults’ intrinsic capacity. This involves evaluating their mobility, cognition, psychological state, nutritional health and the state of sensory faculties such as vision and hearing.

Researchers believe this can make a major difference. Brennan, for one, thinks that screening people in their 40s for frailty traits such as walking speed, grip strength and psychological metrics could improve public health. Rattray is hoping to use some of the accumulating knowledge about the underlying biology of frailty to develop a blood test to screen older adults about to undergo surgery as a way of assessing their resilience.

“If it showed that an individual had enhanced frailty markers… they might benefit from steroids to help with their immune response,” he says. “It could even be a case where they don’t have the surgery in the first place.”

But there’s also much that we ourselves can do to prevent or offset signs of pre-frailty. The sooner we take action, and make tailored adjustments when noticing red flags such as a lack of energy or muscle weakness, the greater the benefits.

Resilience via the gut microbiome

Given that an imbalance of gut microbes has been linked to frailty, dietary changes that encourage microbiome diversity can significantly help. In my book, I outline how consuming more fibre and fermented foods improves gut microbiome diversity and cognitive function in the pre-frail. For example, a 2020 clinical trial involving more than 600 people aged 67 to 79 found that consuming a Mediterranean diet high in plants and fresh foods resulted in a reduction of frailty-associated gut microbes. Other research has found that people who are deficient in key minerals – particularly calcium, magnesium, selenium and zinc – are more at risk of frailty.

Other options may help those who are already frail. For instance, a 2024 clinical trial of the prebiotics inulin and fructooligosaccharides – both forms of soluble fibre – resulted in significant improvements in walking speed and grip strength for frail adults aged over 65.

For particularly severe cases of frailty, Steves is interested in whether more extensive microbiome modulation through faecal microbiome transplants (FMTs) – receiving the gut bacteria of a younger, healthy donor, typically by ingesting samples of their faeces as pills or through a direct infusion into the bowels – can help rejuvenate certain organ systems.

Two years ago, she and her colleagues conducted a clinical trial called CLODIfrail in which very frail older adults with a life-threatening Clostridioides difficile infection in their colon received an FMT. The results showed that it was linked to a short-term fall in the risk of death. “Anecdotally, it improved some other things, other than the C. difficile,” says Steves. “So, some people’s joints felt much better after the transplant, things like that.”

But for midlifers who wish to avoid becoming pre-frail, Steves recommends simple lifestyle changes to avoid aggravating the immune system, such as cutting down on alcohol and getting recommended vaccines. Some studies have suggested that alcohol consumption, and particularly binge drinking, can contribute to the formation of senescent cells, while vaccinations can have wider benefits for the immune system, such as preventing mitochondrial damage from infections.

Exercise is key, too, as it benefits our body, brain and immune system in myriad ways. Daisy Wilson, a geriatrician at the University of Birmingham, says resistance training such as push-ups or lifting weights is a good way to stave off physical frailty by maintaining muscle and bone health. Even very frail people in their 90s can improve their strength.

Furthermore, certain supplements may maximise the benefits of exercise as you age. Some research points to creatine, a natural compound stored in muscles and the brain that is favoured by bodybuilders as it aids energy production during high-intensity exercise and helps build muscle, but which may be particularly helpful in later life. Steves, however, is most interested in the apparent benefits of leucine. This amino acid has been shown in some studies of older adults to help counteract age-related muscle loss, as it triggers a biochemical pathway involved in muscle repair and growth, particularly when combined with vitamin D3.

Anti-ageing therapeutics

As with FMTs, evidence is building – mainly in animal studies – about the various benefits of other anti-ageing therapeutics, sometimes known as geroprotectors, when it comes to preventing or reversing frailty. Geroprotectors range from a group of drugs and plant chemicals known as senolytics, which can clear excess senescent cells from the body, to supplements like nicotinamide riboside (a form of vitamin B3), which is thought to act as a fuel source that can help cells generate new mitochondria.

The race is now on to test these compounds in humans to see whether they can prevent or alleviate frailty. For instance, Wilson is leading a trial of three such potential therapeutics in older adults: metformin (a drug initially developed for type 2 diabetes that is thought to target mitochondrial dysfunction and other hallmarks of ageing), fisetin (a senolytic found in foods such as strawberries) and spermidine (a plant compound present in aged cheese, soya beans, mushrooms, peas and citrus fruits that may boost mitochondrial health).

Initially, each compound is being given to relatively healthy over-70s to see if it improves biological traits such as gut microbiome diversity, immune senescence and mitochondrial fitness. If the results are positive, the next stage will be to test the compounds on over-60s with signs of pre-frailty who are about to undergo surgery for colorectal cancer, to assess whether they prevent worsening frailty following the operation.

Ultimately, if geroprotectors are found to be effective, then the question will be whether they are given to people in middle age, or to people who are extremely frail, says Wilson. “There’s still a lot of unknowns.”

There remains a long way to go, but advances in ageing research could mean we will one day have many more options for addressing frailty. In the meantime, whether it is consuming enough fibre, making time for resistance exercises or keeping alcohol consumption to a minimum, there are many ways to keep stronger for longer.