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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

80-year-old fitness icon Joan MacDonald reveals her simple exercise for a stronger, more stable core

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80-year-old fitness icon Joan MacDonald reveals her simple exercise for a stronger, more stable core

Joan MacDonald didn’t enter a gym until she was 70. Really. Since then, the 80-year-old has transformed her health by losing three stone and building significant muscle, and now coaches other women through her training platform, Train With Joan, which she launched to help others boost their fitness at any age.

The premise of her app is simple: minimal-equipment workouts built around no-fuss, effective exercises that can be done anywhere. One ‘powerful core and stability exercise’ she swears by is alternating bodyweight clock taps. ‘This movement helps strengthen the muscles that keep you stable, balanced and moving well as you age,’ Joan explains.

Bodyweight clock taps benefits

Think they look too simple? That’s the point. Joan is adamant that ‘You don’t need complicated workouts to start getting stronger. Sometimes the most effective movements are the simple ones you do consistently.’

According to Joan, regularly performing bodyweight clock taps help:

  • ‘Strengthen your core which supports your spine and reduces strain on your lower back.
  • ‘Improve balance and coordination, helping you stay steady on your feet.
  • ‘Increase hip stability, which supports your knees and joints.
  • ‘Build functional strength for everyday movements like stepping, turning and reaching.
  • ‘Help reduce fall risk by improving control and body awareness’

@trainwithjoan/instagram//Instagram

How to do bodyweight clock taps

Find a demo from Joan above, along with instructions for how to do them with proper form below.

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  1. Stand on one leg with a slight bend in your supporting knee and brace your core.
  2. Keeping your hips level, reach your free foot forward to lightly tap the floor in front of you (12 o’clock), then return to the centre.
  3. Continue tapping to different “clock” positions—such as 3, 6 and 9 o’clock—maintaining your balance and control throughout.
  4. Complete all reps on one leg before switching sides.

Form tip: Move slowly and focus on staying stable. The goal is controlled movement, not how far you can reach.

How many reps and sets to do

Joan shares her advice, according to your fitness level.

  • Beginners: ‘3 taps per leg x 8-10 reps’
  • Intermediate: ‘3 taps per leg x 10-12 reps’
  • Advanced: ‘3 taps per leg x 12-15 reps’


woman in workout attire featured in women's health magazine for body composition plan.

One of our most frequently asked questions here at Women’s Health? How to build muscle and burn fat at the same time. So, we asked superstar trainer Oyinda Okunowo exactly how to do it. In this 4-week plan – created exclusively for Women’s Health COLLECTIVE members – you’ll get the workouts and nutrition guidance needed to help you on your way to better body composition. Tap the link below to unlock 14 days of free access to Oyinda’s plan and start training today.

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Headshot of Bridie Wilkins

As Women’s Health UK’s fitness director and a qualified Pilates and yoga instructor, Bridie Wilkins has been passionately reporting on exercise, health and nutrition since the start of her decade-long career in journalism.

After earning a first-class degree in journalism and NCTJ accreditation, she secured her first role at Look Magazine, where she launched the magazine’s health and fitness column, Look Fit, before going on to become Health and Fitness writer at HELLO!

Since, she has written for Stylist, Glamour, Cosmopolitan, Marie Claire, Elle, The Metro, Runner’s World and Red. Today, she oversees all fitness content across Women’s Health online and in print, spearheading leading cross-platform franchises, such as ‘Fit At Any Age’, which showcases the women proving that age is no barrier to exercise.

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She has also represented the brand on BBC Radio London, plus various podcasts and Substacks – all with the aim to encourage more women to exercise and show them how. Outside of work, find her trying the latest Pilates studio, testing her VO2 max for fun (TY, Oura), or posting workouts on Instagram.   

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Tim Henman, 51, Has Barely Aged Since Retiring – Here’s His Fitness Formula

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Tim Henman, 51, Has Barely Aged Since Retiring – Here’s His Fitness Formula

In the 19 years since retiring from professional tennis, Tim Henman has barely aged. A large part of that comes down to his approach to fitness. The 51-year-old believes that ‘being active is always going to be a part of my identity’, which helps him maintain a consistent training routine.

Even while spending much of his time covering tennis as a commentator and pundit, and serving on the board at Wimbledon, Henman still makes time for his own athletic pursuits. Especially now that he has a different kind of motivation.

How Tim Henman Stays Fit After Retirement

‘I’ve got a gym at home and I try to exercise pretty regularly because I feel much better for it,’ Henman tells Men’s Health. ‘But one of my passions is wine. So if I’m having a few glasses of wine – you’ve got to treat yourself – then that definitely incentivises me to get in the gym. I’ve always exercised and I think it’s good for me both physically and mentally.’

That doesn’t mean Henman is completing brutal workouts or chasing specific performance goals. Instead, he prefers a straightforward routine that supports his lifestyle and helps him manage the wear and tear accumulated during his tennis career.

‘I don’t run that much anymore. We’ve got dogs at home, so I walk them a lot, and if I’m at tournaments or working, I’ll do quite a bit of incline walking on the treadmill. Then it’s just a good mix of weights and core work. I’m not trying to run any marathons – I’m just trying to stay in relatively good shape,’ he says.

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‘I understand my body and know what I can and can’t do, especially because I’ve had three elbow surgeries and a shoulder surgery. So I’m a little careful around those joints.

‘Posture is so important for shoulder health. I focus on resistance-band exercises to make sure I’m strong through my back and maintaining good posture. Then the core is so important, so I try to stay strong through planks and side planks as much as possible.’

Why Henman Is Excited for the Laver Cup

His approach to fitness has changed dramatically over the past two decades. Where he once played tennis every day, Henman admits he’s now lucky if he gets on court twice a year. These days, golf is his sporting obsession.

That doesn’t mean he’s any less passionate about tennis, however, as he prepares to return as Team Europe vice-captain at the Laver Cup this September at The O2.

‘I’m so excited,’ he says. ‘The first time I ever experienced the Laver Cup was at The O2 when Roger Federer was retiring. I’d never seen the event live and I was probably a bit sceptical at that stage. But I was there working for television and, for those three days, I was completely blown away by the delivery of the event, the intensity of the players and the quality of the matches.

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‘Tennis is an individual sport and players spend most of the year competing on their own. But I’d struggle to name any player, male or female, who doesn’t enjoy being in a team environment every once in a while.

‘The way the Laver Cup has evolved and grown is so special, and Federer deserves a lot of credit for that vision.

‘With an arena like The O2, it’s one of the biggest venues in tennis. There’ll be 17,000 or 18,000 people packed in there and, with the roof on, the atmosphere is incredible.’

Laver Cup returns to The O2, London, from 25-27 September, bringing together many of the world’s biggest tennis stars as Team Europe takes on Team World in the sport’s unique team competition. Tickets are on sale now via AXS, the official ticketing partner of The O2. Visit lavercup.com for more information.


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Ryan is a Senior Writer at Men’s Health UK with a passion for storytelling, health and fitness. Having graduated from Cardiff University in 2020, and later obtaining his NCTJ qualification, Ryan started his career as a Trainee News Writer for sports titles Golf Monthly, Cycling Weekly and Rugby World before progressing to Staff Writer and subsequently Senior Writer with football magazine FourFourTwo.

During his two-and-a-half years there he wrote news stories for the website and features for the magazine, while he also interviewed names such as Les Ferdinand, Ally McCoist, Jamie Redknapp and Antonio Rudiger, among many others. His standout memory, though, came when getting the opportunity to speak to then-Plymouth Argyle manager Steven Schumacher as the club won League One in 2023.

Having grown up a keen footballer and playing for his boyhood side until the age of 16, Ryan got the opportunity to represent Northern Ireland national futsal team eight times, scoring three goals against England, Scotland and Gibraltar. Now past his peak, Ryan prefers to mix weightlifting with running – he achieved a marathon PB of 3:31:49 at Manchester in April 2025, but credits the heat for failing to get below the coveted 3:30 mark…

You can follow Ryan on Instagram or on X  

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Quote of the day by Cher: ‘Nothing lifts me out of a bad mood better than a hard workout on my…’ – motivating life lessons by Oscar-winning actress of Moonstruck and singer of Believe on exercise, mental health, fitness and how this daily habit can transform your mood and mindset

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Quote of the day by Cher: ‘Nothing lifts me out of a bad mood better than a hard workout on my…’ – motivating life lessons by Oscar-winning actress of Moonstruck and singer of Believe on exercise, mental health, fitness and how this daily habit can transform your mood and mindset
Cher quote today: Stress, anxiety, and emotional exhaustion are common parts of modern life, leading many people to look for healthy ways to improve their well-being. While different strategies work for different individuals, regular physical activity is often seen as one of the simplest ways to boost both physical and mental health. Singer and actress Cher shared this perspective in today’s quote of the day, explaining how exercise has become her personal way of overcoming difficult moments.

Quote of the Day Today: Cher on Exercise

Cher said, “Nothing lifts me out of a bad mood better than a hard workout on my treadmill. It never fails. Exercise is nothing short of a miracle,” as per BrainyQuote.

What Cher’s Quote Means: Why Exercise Can Transform Your Mood

Cher’s quote highlights the powerful connection between physical activity and emotional well-being. Rather than seeing exercise as only a fitness routine, she describes it as something that consistently helps improve her mood and clear her mind.

Her words suggest that movement can provide more than physical benefits. A workout can help reduce stress, increase energy, and shift attention away from negative thoughts. By calling exercise “nothing short of a miracle,” Cher emphasizes the positive impact it has had on her own life.

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Life Lesson from Cher’s Quote

The quote reminds readers that small, healthy habits can make a significant difference in everyday life. While exercise may not solve every problem, making time for physical activity can help people feel stronger, calmer, and better equipped to handle daily challenges. Cher’s message encourages people to view exercise not as a chore, but as an investment in both physical and mental well-being.

Who Is Cher

Cher (born May 20, 1946, in El Centro, California) is an American singer, actress, and entertainer whose career has spanned more than five decades. According to a Britannica report, she is known for her success in music, film, and television and for continually reinventing herself.

Cher’s Early Life

Born Cherilyn Sarkisian, Cher faced financial hardships during childhood and struggled with undiagnosed dyslexia. She left school at age 16 and moved to Los Angeles, where she began her entertainment career.

Cher’s Rise to Fame

Cher found success with Sonny Bono as part of Sonny and Cher. Their 1965 hit “I Got You Babe” launched their careers, and she later became a solo star with number one hits including “Gypsys, Tramps & Thieves,” “Half-Breed,” and “Dark Lady,” as per the Britannica report.

Cher’s Acting Career

Cher earned critical acclaim for films including Silkwood and won the Academy Award for Best Actress for Moonstruck (1987). She also starred in Mask, The Witches of Eastwick, Burlesque, and Mamma Mia! Here We Go Again.

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Cher’s Legacy

Cher made a successful music comeback with Believe, winning a Grammy Award for the hit song. She later received Kennedy Center Honors in 2018, was inducted into the Rock and Roll Hall of Fame in 2024, and published Cher: The Memoir, Part One the same year, as per the Britannica report.

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