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Proteomic fitness scores revolutionize disease prediction and personalized exercise plans

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Proteomic fitness scores revolutionize disease prediction and personalized exercise plans

A study published in Nature Medicine journal describes how proteomic scores of cardiorespiratory fitness can help predict disease risk as well as all-cause and disease-specific mortality risks beyond genetic risk scores.

Study Design: We developed and validated a circulating proteomic signature of CRF across four cohorts and various exercise modalities. In the UKB, we examined the relationship a proteomic CRF signature with a broad range of clinical endpoints and examined its interaction with polygenic risk. In HERITAGE, we examined the association of the proteomic CRF signature with response to exercise training and correlated changes in signature with changes in CRF. NAFLD, nonalcoholic fatty liver disease. Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks

Background

Cardiorespiratory fitness (CRF) is a useful prognostic marker of improved health, quality of life, and longevity. Assessing CRF in clinical settings is an effective approach to stratifying disease risk and promoting health.

However, the widespread use of CRF for clinical decision-making is restricted by some factors, including lack of availability and reproducibility of tests and high expenses. Training-responsive biomarkers of CRF is an alternative approach that may address these limitations and enable the identification of pharmacological targets that mimic the effects of exercise.

Exercise induces multiple changes in the metabolic state, which is depicted by changes in blood levels of metabolites associated with CRF. These molecular surrogates of CRF and training responses are associated with clinical prognosis.

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In this study, scientists have established, validated, and characterized a proteomic signature of CRF by linking proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF assessment methods.

They have used data from 22,000 individuals from the UK Biobank to determine the association of the proteomic signature of CRF with a broad range of clinical outcomes (death, cardiovascular, metabolic, malignancy, neurological) and examine its interaction with genetic risk score.

Furthermore, they have used the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study data to evaluate the impact of a 20-week exercise training program on the proteomic signature of CRF.

Proteomic CRF score  

The scientists developed a proteomic CRF score in the Coronary Artery Risk Development in Young Adults (CARDIA) study derivation dataset using exercise treadmill test time as the CRF measure. They further validated the proteomic CRF score across approximately 12,500 participants from four international cohorts. 

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They observed mechanistically reasonable directionality for proteins involved in innate immunity and inflammation, atherosclerosis, neuronal survival and growth, cell physiology, oxidative stress, energy expenditure, and substrate fuel utilization, adiposity, peripheral muscle responses to exercise, and autophagy.

Association between proteomic CRF score and clinical outcomes

The scientists analyzed proteomic profiles and survival data of 21,988 participants from the UK Biobank and observed a significant inverse association between proteomic CRF score and risk of all-cause mortality and disease-specific mortality.

They observed the proteomic CRF score’s consistent and robust protective effect on cardiovascular, metabolic, and neurological outcomes. They found that the proteomic CRF score improves risk prediction beyond standard clinical risk factors, with improved risk reclassification and discrimination.  

By analyzing the interaction between the proteomic CRF score and genetic risk score of common diseases, they observed a significant additive effect between the proteomic CRF score and each genetic risk score on the corresponding disease outcome. The highest disease risk was observed in participants with the lowest proteomic CRF score and a high genetic risk score.

Impact of exercise on proteomic CRF score

The scientists observed an increase in the proteomic CRF score following a 20-week exercise training program. This change was associated with an alteration in peak oxygen consumption, independent of age, sex, race, body mass index (BMI), pre-training peak oxygen consumption, and pre-training proteomic CRF score.

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Specifically, they observed that a higher proteomic CRF score is associated with greater peak oxygen consumption with training, independent of age, sex, and race. However, this association was not sustained after adjusting for BMI.

Furthermore, they observed that the proteomic CRF score components that exhibited significant post-training changes are correlated with a range of metabolic, vascular, and myocardial phenotypes.

Many of these components (proteins) were correlated with adiposity reduction, lipid metabolism, bone morphogenic pathway regulation, and ischemia-reperfusion injury management.

Study significance

The study describes the development of a circulating proteomic signature of CRF using a treadmill exercise test that showed a consistent relation across sub-maximal treadmill exams in 10,320 UK residents and maximal cardiopulmonary exercise exams in 1,587 US residents.

The proteomic signature of CRF exhibits robust and independent associations with a range of metabolic, cardiovascular, and neurological clinical outcomes. These associations seem to be additive to the genetic risk of corresponding diseases. This highlights the utility of proteomic CRF signature for multiomic evaluation of disease and mortality risks.

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The study also highlights the dynamicity of proteomic CRF score following a 20-week exercise training program and an association between training-related changes in the score and peak oxygen consumption. This highlights the utility of proteomic CRF score for personalization of exercise recommendations.

Fitness

The Workout Habit That Can Become Harm

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The Workout Habit That Can Become Harm

If your day begins with a HIIT class and ends with the saintly glow of “I’ve been good,” you’re not alone. Regular movement can lighten stress, settle anxiety, and generally make the world feel a little less like a group chat on deadline. But for a small group of gym-goers, exercise addiction isn’t a punchline or a humblebrag — it’s a real behavioural pattern that can quietly bulldoze daily life.

Researchers in Budapest have suggested that for around 0.3 to 0.5% of gym-goers, working out and the quest for ultimate wellness can tip into unhealthy obsession. And a separate study from Anglia Ruskin University found the risk rises sharply for people with a history of eating disorders — with researchers reporting you’re nearly four times more likely to experience exercise addiction if you’ve previously had anorexia or bulimia.

It’s an uncomfortable twist, because exercise is supposed to be the good bit. The socially approved coping mechanism. The one that gets likes, not concerned phone calls.

Why “Healthy” Can Be a Convenient Disguise

Wellness culture has a curious magic trick: it can make rigid rules look like discipline. Eight hours’ sleep becomes a badge of honour. “Clean eating” becomes a personality. And a workout missed can feel, for some, less like a rest day and more like a moral failure.

That’s what makes compulsive exercise hard to spot — especially during or after recovery from disordered eating. To friends and family, it can look like someone has “sorted themselves out.” Under the surface, the engine can be the same: fear, control, anxiety — just with different gym kit.

As Eating Disorders Awareness Week begins (March 2–8), we spoke to experts about wellness, disordered exercise, and the additional risks for those with a history of eating disorders.

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Can Eating Disorders Be Replaced by Exercise Addiction?

Kerrie Jones, a psychotherapist specialising in eating disorders and clinical director of treatment centre Orri, says eating disorders and exercise addiction often share the same roots — and the same function.

“Eating disorders, like exercise addiction, arise when we have lived through an experience – or lots of different experiences – that have taught us that we’re not safe in our day-to-day lives,” she says.

“Obsessing about food, weight or exercise is a behavioural mechanism that has developed as a means of keeping us feeling safe and in control when otherwise we’d feel overwhelmed with fear and anxiety.”

Jones explains that these behaviours can narrow a person’s focus to what feels measurable and manageable — calories, reps, weight, shape — while masking the deeper fear underneath.

“We call these ‘maladaptive’ coping mechanisms, as they develop through seemingly good intentions, but to the detriment of our longer-term physical and mental health.

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“Sometimes, when people reach a point in their recovery where they are stable and functioning, they may move from an obsessive relationship to food, to an obsessive relationship to exercise.”

And because exercise is widely applauded — and often actively encouraged — the behaviour can stick around far longer than people realise.

“It’s a much more socially accepted and idolised means of maintaining obsessive behavioural patterns,” says Jones, which means it can linger for years before someone seeks help.

What Drives Exercise Addiction Psychologically?

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There’s rarely one neat cause. It’s more often an overlap of biology, social pressure, past experiences, and psychology — with a particular role for trauma and learned patterns of control.

“There’s no one reason or cause why someone might develop an eating disorder or exercise addiction, however, it’s often a combination of social, genetic and psychological factors,” says Jones. “Commonly, we find a negative life experience or traumatic experience at the root.”

Chartered psychologist and Healthspan ambassador Dr Meg Aroll says more research is needed specifically on exercise addiction, but we already know a lot about how behavioural addictions operate — particularly the loop of compulsive thoughts and repeated behaviours.

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“We know that it’s important to change patterns of ruminative and compulsive thoughts in people with behavioural addictions, which is why treatments such as cognitive behavioural therapy are likely to be of help.”

In plain terms: it’s not about willpower. It’s about patterns — and treating what’s driving them.

Signs to Watch For: When Training Turns Compulsive

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There’s no single template for exercise addiction. People don’t present in one uniform way, and “looking fit” tells you precisely nothing about what’s happening mentally.

But there are common warning signs, especially when exercise becomes less about wellbeing and more about relief, guilt, or control.

Jones says a person might:

  • Feel guilt and shame about missing exercise routines
  • Keep secrecy around how much they’re exercising
  • Continue to workout when ill, exhausted or injured
  • Prioritise exercise repeatedly over family, friends, work, and recovery

That last point matters. Training that regularly trumps relationships, rest, or basic health isn’t “dedication.” It’s a red flag waving in fluorescent gym lighting.

Does Social Media Make It Worse?

Social media can be supportive — community can be a lifeline — but it can also validate compulsive habits. A life organised entirely around workouts can look, online, like “motivation,” when the reality might be anxiety management dressed up as routine.

“For people who are predisposed to eating disorders or behavioural addictions, wellness culture can appear to support and condone this type of maladaptive behaviour,” says Aroll.

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“However, on its own, wellness and social media culture is not to blame – someone with such conditions will have a complex combination of factors in their life leading to their symptoms, which should be investigated fully and treated professionally.”

Jones adds that if you know you have an addictive personality, it’s worth curating your feed with intent — and unfollowing content that escalates guilt, restriction, body obsession, or punishment narratives.

What To Do If You’re Worried About Someone

The hardest part is saying something — and the most important part is saying it well. Jones recommends addressing it directly, but with care around timing, tone, and what you focus on.

“It’s important to broach the topic with them directly as their physical and mental health may be severely at risk,” says Jones. “Pick a time to talk when emotions aren’t running high, and where possible, try and avoid talking about exercise specifically or the more symptomatic aspects of exercise addiction or their eating disorder.

“Instead, focus your questions and concerns on how they’re feeling, underneath their day-to-day activities.

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“Keep in mind that there are specialists out there who can help and the charity Beat has numerous resources on how to have a difficult conversation with someone.”

In other words: aim beneath the behaviour, toward the emotion.

Do We Need a Broader Conversation About “Healthy”?

Here’s the tricky bit. Health professionals rightly champion exercise for physical and mental health. But for people recovering from eating disorders — or with a vulnerability to compulsive behaviours — messaging can land differently. “More is better” can become a permission slip for harm.

“I think there needs to be a broader conversation about what it means to be ‘healthy’ and to live a ‘healthy lifestyle’,” says Jones. “What works for some, may not work for others, particularly if they’ve suffered with an eating disorder in the past and would have trouble maintaining a normal relationship to exercise and food.”

Jones says clinicians assessing physical health need to consider personal history and the intention behind the behaviour.

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“If possible, we need to investigate the intention associated with exercise and unpick the feelings that arise before, during and after exercising.”

That’s the real measuring stick. Not calories burned, not streaks kept alive, not the smug serenity of a kale smoothie. If movement helps you live more freely, it’s doing its job. If it’s tightening the cage — especially in recovery — it’s time to call it what it may be: exercise addiction, and something that deserves proper support, not applause.

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I’ve seen some bizarre exercises online. If I were an influencer, this is the one workout I’d recommend | Devi Sridhar

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I’ve seen some bizarre exercises online. If I were an influencer, this is the one workout I’d recommend | Devi Sridhar

Are you still keeping up with your 2026 resolution to exercise more? Or perhaps you’re just trying to survive the winter doldrums, with exercise the last thing on your mind. Whatever it is, social media is alight with fitness influencers showing off all kinds of bizarre and viral exercise trends.

Take squats, a core exercise move. Those don’t seem good enough any more, so now we have Zercher squats (holding a barbell in your elbow crease like a metal baby), squats on vibration plates, squats while throwing a heavy ball and on and on. Some of these exercises may in fact be good, some useless, but because influencers can’t be seen to be doing the same thing every day, the key thing is that they’re novel and can be sold as “the little-known secret exercise that everyone should be doing”.

Then there’s adding a gimmick to an existing exercise. There’s goat yoga, puppy yoga and – my favourite new trend from the US – snake yoga, in which snakes such as pythons slither around the room and on to mats and yogis while they’re in downward dog thinking about spiritual intentions or, more likely, what’s for dinner. The marketing is that being around snakes in yoga can help overcome a fear of snakes while also building flexibility. Cross two things off your to-do list at once!

Here’s my public health take: fear of snakes is rational. About 5.4 million people are bitten by snakes each year. Evolution spent thousands of years instilling that fear in us – for good reason.

Why do bizarre fitness trends go viral, and why do they appeal to something within us? I think it has to do with boredom, the need for novelty and Fomo. Exercise can feel boring: going out running for the same 5k or heading to the gym to the same equipment and space. This is true also for yoga, which can feel slow and lack excitement.

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The idea of trying something new is appealing, plus there is a constant push by certain fitness influencers implying that they know something we don’t. Some of them play on health anxiety and a desire to optimise with the “best” exercise to maximise your time and results: how to get a six-pack in two weeks or how to lose 10kg in five days (both pretty much impossible, by the way). Plus they’re telling us to buy a supplement or try a new juice cleanse that will be the missing piece to make us feel better by March.

Fitness trends sell that hope of feeling better. Take Hyrox, a hybrid endurance event where super-fit people pay good money to push sleds, throw wall balls, burpee-jump across the room and run between various stations. It’s impressive to watch and looks great on social media – which feels essential these days – and it’s a clear way to show your friends how fit you are. But it also reflects the push towards extreme, complicated and injury-prone exercise.

I’m going to say something you don’t want to hear, especially if you love Hyrox or snake yoga: none of this is necessary. If your goal is to feel strong, move better, stay pain free and live longer, you need three things: cardio exercises, resistance training and mobility training.

You don’t need weights, reptiles or cameras. It sounds simple, but what makes exercise hard isn’t the actual movement. It’s finding the time and routine to make it sustainable and part of your daily life. Which brings me to the most untrendy thing I can offer you: a 13-minute workout you can do anywhere, with or without weights. This is my default on busy days, and when I’m at home I have an 8kg sandbag on hand to add in.

All you need is a timer on your watch or phone. Start with three minutes of cardio to get warm and your heart rate up, whether it’s jogging on the spot, jumping jacks or just marching. Then it’s three minutes of legs, rotating between five each of narrow squats, broad squats, backward lunges, forward lunges and calf raises. Then on to three minutes of upper body, moving between five each of narrow push-ups, wide push-ups and tricep dips. Time to move on to core with a one-minute plank (either on your hands or forearms) and one minute of glute bridges (lifting your hips off the floor while lying on your back). For the final two minutes, just stretch out, whether that’s standing and reaching for your toes, lying on your back and moving your legs right and left like windshield wipers or sitting cross-legged and folding forward.

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That’s it. Do this a couple of times a week if you can. Will you see it go viral on socials? No. Will it get sponsored by a supplement company? No. Will it increase your healthy life expectancy and make you feel happier? Public health evidence suggests yes. The real challenge, it turns out, isn’t finding the latest hack or trend. It’s sticking with a (snake-free) routine, even when the novelty wears off and 2026 resolutions fade from memory.

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The exercise more important than walking – especially if you’re older

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The exercise more important than walking – especially if you’re older

Walking is brilliant. It’s accessible, affordable and enjoyable, plus it comes with many health benefits, which is why it forms the backbone of most government exercise guidance.

But it is strength that underpins all movement. If you don’t have the strength to get out of your chair and put one foot in front of the other, what good is being told to walk more?

This was the key takeaway from recent research led by Dr Michael LaMonte and his team at the University at Buffalo, which shows the immense value of building skeletal muscle with strength training. It found that, in more than 5,000 women aged 63 to 99, greater strength levels were strongly linked to a lower risk of death from any cause.

Maintaining muscle should be seen as a savvy investment. Muscle allows you to stand, move and remain independent, all while offering further perks that extend far beyond physical function. It powers our breath, regulates blood sugar levels, emits anti-inflammatory myokines and constantly chats with other bodily systems to keep things running smoothly. In short, muscle is the medical marvel you already own.

Here is how to maintain your body’s largest, and in some ways smartest, organ for decades to come.

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Why strength training matters

There is a wealth of research on the merits of aerobic exercise, such as walking, running, swimming and cycling. This is a major reason why it dominates government physical activity guidelines. There is far less research into strength training, and much of the data available centres around young, fit men.

By looking at the impacts of strength training in previously understudied demographics, such as women aged 60 and above, studies like this one from the University at Buffalo could change future exercise recommendations for the better.

“When women go through menopause and lose their body’s own secretion of oestrogen, the loss of skeletal muscle mass increases rapidly,” says Dr LaMonte. “We typically see a change in their body composition, where they start losing muscle and holding fat in the belly area, particularly. That’s not healthy.”

Both men and women also tend to become less active as they grow older, which can contribute to sarcopenia – the age-related loss of strength and muscle. Both menopause and sarcopenia are inflammatory processes, Dr LaMonte says.

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Read more: Sitting all day wreaks havoc on your hips and spine – here’s how to stop that from happening

There is limited research around strength training in older populations – but that is changing (Getty/iStock)

This shift impacts fitness. “Muscle strength is fundamental for getting the body from point A to point B, especially when you’re working against gravity.” But it also throws off chemical signalling between skeletal muscle and other systems in the body, such as the heart.

“Fat tissue tends to secrete chemicals called cytokines that are pro-inflammatory,” Dr LaMonte explains. “There’s quite a bit of evidence to show that, when skeletal muscle contracts, it secretes counterbalancing cytokines that are anti-inflammatory.

“This was discovered by a scientist named Bente Pedersen in the 2000s. She published a compelling series of papers showing that these cytokines, which she called myokines, had regulatory functions outside the muscle itself.”

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Exactly how skeletal muscle interacts with other crucial systems in our body is unclear, Dr LaMonte says. But it is constantly in deep discussions with them, and it is looking to help out where it can. For this reason, if you can keep your muscles strong and healthy, they can be a powerful force for good.

Read more: Expert warns why this daily habit is shortening your life – even if you exercise

Maintaining healthy muscle not only ensures independence and physical capacity, it can also lead to deeper-lying health benefits

Maintaining healthy muscle not only ensures independence and physical capacity, it can also lead to deeper-lying health benefits (Getty/iStock)

3 simple ways to gauge your strength

Dr LaMonte’s research used a series of simple tests to assess the strength levels of 5,472 women aged 63 and above:

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  • Grip strength: a dynamometer was used to assess grip strength, with people asked to hold their upper arm at their side, elbow bent at a right angle, then squeeze the machine as hard as possible. This is an indication of upper-body strength.
  • Sit-to-stand: people were timed to see how quickly they could stand up from a chair, then sit back down again five times with their arms across their chest. This is an indication of lower body strength.
  • Gait speed: a timer was used to see how long it took subjects to walk 2.5m.

Women with greater grip strength – a good signifier of overall strength levels – and faster sit-to-stand times had a “significantly lower death risk over an eight-year follow-up”, the study discovered.

“Gait speed is another one of the most potent predictors of mortality,” Dr LaMonte adds.

“I’d like to see the health care profession embrace functional health as much as they do the things they can prescribe drugs for – because you can’t prescribe a drug for this. It’s a behaviour, and I think that’s why it probably doesn’t get the same kind of attention. Nobody makes money from this, but people do die from it.”

Dr LaMonte also suggests another bonus test anyone can use as a sign they need to work on their strength levels:

  • The pickle jar test – this is a proxy for any everyday task. If you notice it starts to feel more difficult, this is a good indication that your fitness has decreased, and it would be beneficial to gain strength and muscle through exercise.

“When you can’t open the pickle jar any more, don’t just assume they’re making the jars harder to open,” Dr LaMonte says. “That’s a good indicator that you might be at a phase of life where your strength levels have changed unknowingly.

“The same applies when you go to pick up a grandchild or climb the stairs, and you find you’re huffing and puffing – it could simply be that you’re getting more out of shape, or in the worst case scenario, it could be indicative of disease.

“Be mindful of your body. It’s going to tell you where you’re at, and we don’t want an injury to be that indicator.”

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Read more: Four things you can do to reduce inflammation and cut heart disease risk, according to the experts

When daily tasks such as climbing the stairs start to feel markedly harder, it could be a sign that your strength levels are decreasing, Dr Michael LaMonte says

When daily tasks such as climbing the stairs start to feel markedly harder, it could be a sign that your strength levels are decreasing, Dr Michael LaMonte says (Getty/iStock)

How to start strength training at any age

The human body is a representation of the life it has lived, informed by genetics and altered by myriad interventions along the way. A robust life, filled with challenging physical tasks, often builds a robust body. As a result, someone who has always been active will likely find it easier to remain more active as they age.

“I wouldn’t want to convey a message that age becomes a constraint for people doing what they enjoy,” says Dr LaMonte. “I know people in their late, late years who still enjoy going to gyms and lifting weights. It’s effective for their strength goals, and the social aspect keeps them healthy in other ways.”

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However, if you are new to strength training and exercise generally, you need to start more conservatively. As with any new skill, there is an obligatory learning curve that allows your mind and body to adapt to the fresh stimulus without being overwhelmed.

“You can use simple bodyweight exercises like press-ups against a wall or sit-to-stands – US adults in their 70s and 80s spend around nine-and-a-half hours each day sitting down, so you could break this up by doing a few sit-to-stands every hour, or each time there is an advert if you are watching television,” Dr LaMonte says.

“Resistance bands are another good option, or even using soup cans or books as a form of resistance provides stimulus to skeletal muscles.”

The common denominator behind these exercises is the act of overcoming resistance. That resistance needs to be slightly challenging, relative to your individual strength levels, to trigger an increase in muscle and strength levels. By consistently doing a task that requires you to be stronger, you are telling your body you want it to adapt to handle it better. If the task feels easy, the body has no reason to make any changes.

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“If someone finds that lifting a soup can or book [for example, pressing it overhead 10 times] challenges them, that’s probably the level they should be working at, and they should not be trying to do more,” says Dr LaMonte. As you grow stronger, you can then gradually progress to slightly heavier items to continue to increase your strength levels.

“Older adults in particular should consult with their health care provider about the safety of beginning muscle-strengthening exercises,” Dr LaMonte adds.

In short, building and maintaining strength is important at any age. And if you do fall below this study’s 63-99 demographic, any strength and muscle you can develop now will likely serve you well for the rest of your life.

“We want to live as long as we can healthily, and I think resistance exercises are a part of that,” Dr LaMonte concludes. “When we can no longer get out of the chair and move around, we are in trouble.”

Read more: After 50, you need to train smarter – the eight rules for strength training in midlife, according to experts

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Read more: The science-backed two-minute daily workouts for improving heart health

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