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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.

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A trainer says returning to exercise in your 40s and 50s should look different to what you did in your 20s—here’s how to get started again

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A trainer says returning to exercise in your 40s and 50s should look different to what you did in your 20s—here’s how to get started again

After a period of inactivity, getting your fitness back can feel like a tough slog.

Jason Smith, a personal trainer, nutritional advisor and founder of Fit in Midlife, knows this from personal experience. He got fit again at 50 after years of inactivity, then started training people of a similar age, helping them to do the same.

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Enter 2026 stronger than ever with these expert-approved fitness tips

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Enter 2026 stronger than ever with these expert-approved fitness tips
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Whether you’re focused on building muscle, improving your balance or working on your ability to complete longer, sustained workouts, one thing’s for sure: you’ll need to take small, actionable steps to reach your fitness goals.

Remember, you don’t need to drastically overhaul your life on January 1. In fact, before making any major changes to your dietary pattern and exercise routine, it’s best to have a conversation with your doctor first, especially if you live with any chronic conditions. In the long run, you’ll most benefit from taking small, actionable steps to help achieve your fitness and nutrition goals, the experts say.

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We asked fitness experts to break down their top tips to help you kick off 2026 stronger than ever.

How to fit exercise into a busy schedule

If you’re hitting the reset button on your fitness routine, start small and choose an exercise you enjoy, says Dr. Kimberly Burbank, a primary care sports medicine fellow and team physician at UCLA Athletics. You don’t necessarily need to do the movements traditionally associated with exercise to get a good workout in, either. “I really encourage people to choose (a movement) they actually enjoy doing, because they will probably stick with it more,” she says.

To help set attainable fitness goals, one route is to use the SMART framework of goal setting, recommends Dr. Brandee L. Waite, a professor and vice chair of Wellness & Community Engagement Department of Physical Medicine & Rehabilitation at UC Davis School of Medicine, the medical director of the UC Davis Health Sports Medicine Clinic and the director of Lifestyle & Longevity Medicine Innovation.

The SMART acronym stands for goals that are specific, measurable, attainable, realistic and time bound, and what’s great about using this framework in an exercise context is that you’re able to approach fitness as you would any other appointment — if it’s scheduled on your calendar, there’s a greater likelihood you’ll honor it, Waite says.

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When it comes to fitting exercise into a busy schedule, “I try to encourage consistency over perfection,” Burbank says. Often, her patients will express frustration that they’ve missed a week of exercise — and therefore their entire workout schedule has been thrown off. While it’s important to “be as consistent as you can, (understand) that you don’t have to be perfect to still make a meaningful difference,” she says.

If you’re someone who prefers to exercise in the morning, try to make it easy for yourself when you wake up. “It’s so easy when that alarm goes off to just ignore it and move on. But if you have laid out your clothes the night before, have your coffee prepped (and) have your bag packed, then there’s so many (fewer) variables and barriers,” Burbank says.

How often should you exercise?

There’s no perfect cadence as to how often you should exercise. “What works really well for one person, will not work at all for another person. So, it does need to be personalized and realistic,” says Waite. However, there is something to be said about shorter, more frequent workouts. There’s a lower risk of injury, and they’re faster to complete and generally easier to stay consistent with, Burbank says.

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Ultimately, what’s most important is to meet a certain number of goal minutes every week, says Dr. Julia L. Iafrate, a sports medicine physician at NYU Langone Health and a team physician for the U.S. Ski Team. The Physical Activity Guidelines for Americans and the American College of Sports Medicine recommend adults participate in 150-to-300 minutes of moderate-intensity exercise a week. While this might sound intimidating, that breaks down to only 30 minutes of exercise a day over the course of five days, and could consist of a mix of pilates, yoga or brisk walking.

If you prefer vigorous-intensity aerobic exercises (like HIIT or running), it’s recommended you complete at least 75 minutes a week, which evens out to a little more than 20 minutes of exercise a day over the course of three days. On top of these exercises, the organizations suggest adults should partake in muscle-strengthening workouts at least two days a week.

What are the most beginner-friendly exercises?

There are a few forms of exercise that should be a central focus of your workouts: cardio, muscle strengthening and balance work. Practicing each type of exercise can help improve your ability to do the others and also reduce your risk of injury, Iafrate says.

  • Cardio. Incorporating aerobic exercises that get your heart rate up (such as running, swimming or cycling) is key to improving endurance, supports heart and lung health, and lowers your risk for a number of chronic diseases, Iafrate says. 
  • Muscle strengthening. Resistance training with weights stimulates two types of muscle contractions: eccentric loading and concentric loading. When you perform a bicep curl with a dumbbell in hand, that’s considered a concentric motion. As you lower the dumbbell and your arm straightens, that is an eccentric motion, Iafrate says. Both movements are important for strength building, tendon health and bone mineral density, she explains. 
  • Balance work. Functional movement training, including tai chi and yoga, is especially beneficial for maintaining flexibility, stabilizing your body and limiting the likelihood of falls down the line, Iafrate says. 
  • Weight-bearing exercise. “Walking, especially for beginners, is super underrated,” Burbank says. Getting your step count up to 7,000 steps a day offers immense benefits for health, including lowering your risk for cardiovascular diseases and type 2 diabetes, according to a 2025 study published in Lancet Public Health.

If you’re relatively new to exercise and don’t know what is helpful or harmful, Waite recommends having at least two-to-three sessions with a physical therapist to develop the right type of exercise program. For instance, if someone has a medical condition like hip arthritis, a professional can provide “modifications for a regular fitness training program that won’t further exacerbate the problem that is currently bothering them,” Waite says.

How can nutrition support fitness goals? 

“Nutrition and exercise have such a symbiotic relationship,” Burbank says. Throughout your week, prioritize whole, fiber-rich foods, including fruits, vegetables and whole grains. Americans aren’t consuming nearly enough protein, which is essential to muscle building, muscle recovery and satiety, Burbank notes. Your minimum daily intake of protein should hover between 0.8 grams to 1.2 grams of protein per kilogram of body weight. To increase your protein intake, the Dietary Guidelines for Americans 2020-2025 recommends incorporating more lean meats, poultry, eggs, seafood, legumes, nuts, seeds and soy into your diet.

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Hydration is particularly important, especially prior to working out. “When you’re dehydrated, (it will) increase your likelihood for fatigue and poor peak performance,” Iafrate says. Ideally, we should be drinking between 2.5 to 3 liters of water a day, Burbank says. 

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New Year’s Fitness Goals: Avoid These Common Mistakes

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New Year’s Fitness Goals: Avoid These Common Mistakes

A new year usually brings new fitness goals, fueling spikes in gym memberships and social media feeds filled with workout selfies. Yet, just as quickly as this wave of motivation appears, it usually recedes.

Why does this cycle repeat itself year after year? Well-meaning individuals often start with intense, all-or-nothing approaches that are difficult to sustain, fitness experts say. Life gets in the way, motivation wanes, and the pressure to see immediate results leads to burnout.

A commitment to fitness is a common challenge, and finding a solution is crucial for long-term success, according to Steven Hale, M.D., a primary care sports medicine physician with Baptist Health Orthopedic Care. To get expert advice on this topic, award-winning journalist Johanna Gomez hosted a new Baptist Healthtalk podcast featuring Dr. Hale.

He emphasizes that the most effective plan is one that fits into one’s life seamlessly.

“If it’s in your schedule every day, then you’re going to have to do something active,” Dr. Hale explains. “Whether that’s mobility, maybe you only have 20 or 15 minutes to stretch. Maybe you have an hour this one day because you got off work early. Now you can do some more strength training and maybe some increased cardio.”

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This approach shifts the focus from overwhelming daily workouts to simply incorporating movement into your daily schedule. Building on this foundation of practical advice, Dr. Hale answered some of the most common questions about starting a new fitness routine.

I haven’t worked out in a long time. What’s a good way to start without getting overwhelmed or injured?

Dr. Hale: It really depends on your previous activity level and experience with exercise. Someone who was a college athlete or has a lot of experience can probably go back to the gym, start with lighter weights, and build from there. For someone who is less experienced or doesn’t enjoy the gym environment, I often recommend starting at home. You can look up fun follow-along exercise videos on platforms like YouTube.

Classes can also be a great option for those new to exercise, as they provide guidance from instructors. Personal trainers are another fantastic resource if they fit your budget. The key is to start slow to minimize your risk of injury. Don’t go too hard in the beginning. The first few workouts might not feel great as you get back in shape, so making it fun and enjoyable will help you stick with it longer.

Diet and exercise are both important, but which one should I focus on more if I want to see results?

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Dr. Hale: As a doctor, I have to say they go hand-in-hand; I can’t recommend one without the other. Diet is just as important, if not more important, than exercise when it comes to seeing results quickly. In the short term, diet probably has a slight edge. We often talk about creating a calorie deficit for weight loss, which means the calories you consume should be less than the calories you burn.

It’s much easier to consume calories than it is to burn them. A single high-calorie meal can easily undo the effort of an hour-long workout. However, for long-term health, diet and exercise are equally important. What you put into your body for nutrients is just as vital as staying active. Instead of overhauling your entire diet at once, which is hard to stick to, try making one small, manageable change each week. For example, cut out one specific snack food or fast-food meal. This slow progression helps you build sustainable habits.

How do I know the difference between normal muscle soreness and an actual injury?

Dr. Hale: It’s a great question because many people enjoy the feeling of being sore after a good workout — it’s like a victory. Soreness is typically a dull ache that you feel after exercise, and it usually goes away within a few days. Pain that should concern you is more severe. On a pain scale of one to ten, anything greater than a three is something to pay attention to.

Concerning pain might also be sharp, or you might have felt a ‘popping’ sensation during your workout. Other warning signs include mechanical symptoms like a joint feeling unstable or locking up. These are more serious symptoms that indicate you should probably see an orthopedic specialist. It’s important to listen to your body and not push through sharp or worsening pain.

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The phrase “no pain, no gain” is very popular. Is it true that I need to push through pain to make progress?

Dr. Hale: That is one of the first myths I address in my practice. The “no pain, no gain” philosophy is not a good approach for orthopedic health. If you feel pain, it’s a sign that there is inflammation in that area. Pushing through that pain will only worsen the inflammation and delay your recovery.

Instead of pushing through it, pain is a signal from your body to rest or modify your activities. Give the affected area time to heal and for the inflammation to calm down before you return to that specific exercise. If you continue to push through pain, you risk causing the issue to last longer or become more severe. You can likely push through discomfort that is less than a three out of ten on the pain scale, but anything more than that requires attention.

I want to stay consistent, but I’ve heard working out every day is bad. How often should I be exercising?

Dr. Hale: This depends on how you define ‘workout.’ If you’re doing intense strength training where you are really stressing your muscles, those muscles need time to recover. Overtraining can lead to inflammation, pain, and a higher risk of injury. In that case, you need to build recovery days into your schedule.

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However, you can and should do something active every day. I recommend having something in your schedule daily because it makes it harder to use excuses and push it off. We can think of these as ‘mobility days’ versus ‘strength days.’ A mobility day could be stretching, yoga, or going for a walk. A strength day involves more intense activity like lifting weights or jogging. For example, a good plan could be three or four strength training days per week with active recovery like walking on the other days. This way, you are moving your body every day while still giving your muscles time to recover. Any activity is beneficial.

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