For those who haven’t hit them yet… brace yourselves for the ages of 44 and 60.
Whereas the previous thinking was that ageing is a linear, gradual process, recent research suggests that it in fact hits you hardest at these two distinct points of your life.
It’s then that the middle-age spread might really attack, for instance, and rather than being able to drink the night away, hangovers hit you even harder. That cup of coffee you used to unthinkingly down after lunchtime might now keep you awake at night, too.
But the good news is that there are measures you can take to combat these sudden shifts (more on this later).
The latest insight comes from a study published in Nature Ageing, which aimed to pinpoint the changes that happen at a molecular level that underlie the ageing process.
Researchers at Stanford University in the US took blood, saliva, nasal, stool and skin samples from 108 healthy 25 to 75-year-olds, every three to six months, for around seven years.
They monitored various markers including changes in the microbiome – the community of microbes found within the gut, nasal passages and mouth – as well as levels of cytokines, which are proteins that control inflammation (known to play a part in ageing and many diseases).
The researchers found that, whereas minor changes occurred year on year, the dramatic changes occurred at the ages of 44 and again at 60 – and that applied to everyone: men and women.
Dr Edouard Debonneuil, an expert in cardiopulmonary ageing based at the London Longevity Clinic
They found, for example, that at these ages the levels of damaging proteins linked to plaque build-up in the arteries shot up, as did levels of enzymes associated with combating inflammation – indicating that levels of inflammation were also rapidly rising.
What’s more, the strength and thickness of the skin and muscles started to decline at both 44 and 60 – bad news for those hoping to hold off the wrinkles and bingo wings.
The findings suggest ‘we do more ageing in our 40s and 60s than in the rest of our life span,’ says Adam Gordon, a professor of the care of older people at the Academic Centre for Healthy Ageing at Queen Mary University of London.
‘This has some sort of plausibility to it, because if you look at your friends and family, you can see that people do seem to age more rapidly from their mid-40s.’
What’s more, he says, it adds weight to the theory being backed by increasing research that we don’t ‘age roughly the same amount each year and our biological processes undergo constant and predictable change’.
This new study is the first to identify such a significant shift in the ageing process at 44 and 60. Professor Gordon says this new finding should be ‘a call to arms that there’s a period in life when we are going to be vulnerable to ageing and that’s a good time for us to be looking at our lifestyle choices, the decisions we make and doing what we can to try to age in as healthy a way as possible.’
Here’s how to do it…
SHORT JOG CAN OFFSET CELL DAMAGE AT 44
At the age of 44 the researchers found that not only did cardiovascular ageing accelerate (with more molecules that have the potential to do damage in the blood vessels circulating, for example), so too did insulin resistance (when the body does not respond to insulin, which controls blood sugar levels) and oxidative stress – which can lead to cell and tissue damage.
‘When you look at those three clusters together, the thing that can modify them is doing regular exercise,’ says Professor Gordon.
‘If you do regular exercise, you’re less likely to develop insulin resistance, less likely to put on weight and less likely to develop cardiovascular disease – and some of the chemicals that are released in your body during exercise help combat the effects of oxidative stress.’
A 2011 study in Taiwan showed that even 90 minutes of exercise per week could improve lifespan (picture posed by model)
The experts agree that it’s best not to be a weekend warrior and instead to spread out the NHS guidelines of 150 minutes of moderate exercise across the week – to leave enough time for our bodies to recover between workouts.
Dr Edouard Debonneuil, an expert in cardiopulmonary ageing based at the London Longevity Clinic, says: ‘The best option is to do aerobic activity [such as jogging] for half an hour, two or three times a week – and leave two or three days for the body to regenerate.’
A 2011 study in Taiwan showed that even 90 minutes of exercise per week could improve lifespan, while a 2024 study showed people who exercised three times a week had lower incidences of sarcopenia (age-related muscle loss).
CUT BACK ON ALCOHOL AND COFFEE
The new study also discovered that at 44 our ability to break down caffeine, alcohol and fats slows – meaning that cup of coffee or extra glass of wine is going to linger for longer, with knock-on effects for our health.
‘We may metabolise alcohol or caffeine more slowly, so smaller amounts may have a more marked effect and by-products of alcohol metabolism may linger in the system – potentially doing more harm to your liver,’ says Professor Gordon.
When it comes to alcohol, ‘most of the evidence now suggests the risks are much greater than we perhaps realised even a decade ago’, says Professor Gordon.
So for those approaching their mid-40s, he suggests ‘you adhere to 14 units and make sure you have two or three alcohol-free days a week, to recover’.
‘As for caffeine, if we are not metabolising it so well it could contribute to heart problems or interfere with the sleep/wake cycle,’ he says.
To offset this, Professor Gordon suggests cutting back and ideally having no more coffee after lunchtime.
APPROACHING 60? BOOST YOUR PROTEIN
The study authors found that among the key changes in our 60s was a shift in the ability to break down carbohydrates, which means it’s harder to burn the energy we gain from carbs. Any excess is stored as fat, leading to weight gain.
Professor Gordon says this tallies with other research that has found our protein requirements increase as we age, to make up for the muscle loss we experience from our 40s and which speeds up in our 60s – known as sarcopenia.
Dr Dariusz Sołdacki, an immunologist and scientific director of the Longevity Centre Europe based in Zurich, Switzerland
‘There’s evidence that we need to increase our protein intake as a proportion of the overall calories we consume, as we age,’ says Professor Gordon. ‘This evidence that we metabolise carbohydrates less well adds weight to that line of thinking.
‘So, as you grow older, you might want to take less of your calories as carbohydrates – so fewer potatoes, pasta and starchy vegetables – and take, for example, more eggs, dairy and bean-based vegetables that are rich in protein, in order to respond to your changing metabolic needs.’
Dr Debonneuil says he always has sardines for breakfast for this reason (he is 44).
‘They have bones which are a better source of calcium than milk. They have the skin [which provides anti-inflammatory omega-3 oils] which is beneficial for your skin, and they contain protein, so you’ll feel satisfied and don’t have this sugar spike that’ll need insulin to make it go down and make you feel tired mid-morning.’
BOLSTER YOUR IMMUNE SYSTEM AND MUSCLES
The immune system also underwent a significant change at 60, according to the study, meaning both everyday infections and chronic diseases become more likely.
Professor Gordon says: ‘We’ve known for a long time that immune function changes as you age. The new study showed that there is quite a significant step change in our early 60s.
‘This explains some of the vulnerability that we see in people in their early to mid-60s onwards to winter infections, and acts as a reminder for people to get their winter vaccines – for example, for flu – in time.’
Exercise can also help, says Dr Dariusz Sołdacki, an immunologist and scientific director of the Longevity Centre Europe based in Zurich, Switzerland.
‘Our thymus [a small organ located in the upper chest which makes and ‘trains’ our immune cells] shrinks as we age and our training for immune cells gets weaker,’ he says.
‘But we can stimulate our immune system by moving – studies show that after less than an hour of moderate exercise, you have 15-20 per cent more immune cells circulating in your system than before.’
A 2021 study showed that performing moderate-intensity exercise – in this case, a warm-up followed by 20 minutes of aerobic activity (jogging, swimming, etc.) and then weight-bearing exercise such as squats and press-ups – could retune the immune system and improve the immune response, which would perhaps even delay or reverse the decline of immune system function. It also led to fat loss and improved body composition.
This is also a good time to ensure you keep properly hydrated, says Dr Sołdacki.
‘In your late 60s and beyond you can be less aware of the sensation of thirst and therefore drink less water,’ he says. ‘With less water, there is a lower filtration rate, and the kidneys can’t function properly.’
Dr Debonneuil advocates investing in smart body composition scales, which give an indication of muscle mass – and losing our obsession with weight loss per se.
‘Focus on building muscle mass by lifting weights or doing resistance training. This causes muscles to secrete myokines (proteins that repair damaged tissue) locally and in the blood, and some myokines are thought to be behind the anti-tumour role of physical activity which has been observed in animals and people.’
ANTI-AGEING DRUGS ROUND THE CORNER
Currently, there is much excitement around the idea of senolytic drugs, which destroy cells that accumulate with age and lead to chronic diseases.
’There is the possibility in the future that we will uncover drugs that can slow the ageing process in a very general way by targeting specific metabolic pathways such as those identified recently that speed up ageing at 44 and 60 – and switch them off,’ says Professor Gordon.
‘You might find that there’s a drug that not only makes you look a bit younger, but also helps you be able to exercise a bit more, cope with more stress and metabolise nutrients better.
‘And it could be that, in the future, we identify people at points in their life when they’re approaching one of these ageing transitions, and we give them medication to prevent some of the worst effects of ageing – in much the same way that we give statins currently to reduce cardiovascular risk.
‘But that’s still some time off. For now the best thing is to focus on what you eat, how much exercise you do and the amount of alcohol you drink.’
