Yijinjing Exercise for Musculoskeletal Health in Adults With Sarcopenia

This multicenter, assessor-blinded study will enroll 240 adults aged 50 years or older with sarcopenia. The two lead centers are Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, and Beijing Jishuitan Hospital, Capital Medical University. Participating centers are Xuanwu Hospital, Capital Medical University; Beijing Friendship Hospital, Capital Medical University; China-Japan Friendship Hospital; and Beijing Luhe Hospital, Capital Medical University. The study is jointly led by principal investigators Yuchao Liu and Wei Tian.

The study uses a two-stage randomized design. During months 0-6, participants are randomized in a 1:1 ratio to modified seven-form Yijinjing or progressive resistance training. The first-stage objective is to evaluate whether Yijinjing is noninferior to resistance training for change in the Short Physical Performance Battery (SPPB) total score from baseline to 6 months. SPPB scores range from 0 to 12, with higher scores indicating better performance. The prespecified noninferiority margin is 0.5 points: noninferiority is concluded if the lower bound of the 95% confidence interval for the between-group difference in change (Yijinjing minus resistance training) exceeds -0.5 points.

Stage 1 Yijinjing sessions last approximately 40-45 minutes, including warm-up and cool-down, three times weekly. Resistance training is performed at least three times weekly for approximately 40 minutes per session and includes five functional exercises for major muscle groups. Weekly delivery consists of one supervised group session and two remotely supervised home sessions. Exercise technique and intensity are adjusted for tolerance and safety.

After the 6-month assessment, all participants originally assigned to resistance training switch to standard-duration Yijinjing for months 7-12. Eligible participants originally assigned to Yijinjing undergo a second 1:1 randomization to standard-duration Yijinjing (40 minutes per session) or extended-duration Yijinjing (progressively increased to 50-60 minutes, with a maximum of 65 minutes including warm-up and cool-down). Both schedules involve three sessions weekly. Original Yijinjing participants who do not meet the prespecified criteria for the second randomization continue standard-duration training if clinically appropriate; they are distinguished from re-randomized participants in analyses. Thus, the three registered treatment pathways arise from the two-stage design rather than an initial three-group randomization. The second stage explores the effects of session duration and longer-term intervention.

All participants receive standardized dietary counseling and health education. Dietary advice targets protein intake of 1.2-1.5 g/kg per day through ordinary food, using the lower of ideal or actual body weight. The study does not supply protein supplements. Health education is delivered weekly during the first three weeks, with identical content and contact time across groups.

Assessments are scheduled at baseline, 6 months and 12 months. In addition to the primary 6-month SPPB endpoint, outcomes include muscle mass index, handgrip strength, walking and chair-stand performance, 12-month SPPB change, quality of life, frailty, cognition, depression and anxiety. Bone mineral density measurements are collected at the two lead centers. Circulating biomarkers are assessed for exploratory mechanistic analyses. Adverse events are monitored throughout the 12-month intervention. Outcome assessors, data managers and primary statistical analysts are blinded to allocation; participants and exercise instructors cannot be blinded.

Enrollment is anticipated to begin in January 2027. Primary outcome collection is expected to finish in September 2028, and 12-month follow-up is expected to finish in March 2029.

• Modified Yijinjing Exercise (Behavioral): Modified seven-form traditional Chinese exercise adapted for adults with sarcopenia, combining movement, breathing and attention. Three sessions weekly: one supervised group session and two remotely supervised home sessions. Stage 1 sessions last 40-45 minutes including warm-up and cool-down; stage 2 standard-duration sessions last 40 minutes and extended-duration sessions progressively increase to 50-60 minutes, maximum 65 minutes. Target Borg RPE is 11-13 on the 6-20 scale. Duration and movement intensity are adjusted for tolerance and safety.
• Progressive Resistance Training (Behavioral): Six months of progressive resistance training at least three times weekly, approximately 40 minutes per session: 5 minutes of warm-up, 30 minutes of exercise and 5 minutes of cool-down. Five functional exercises target major muscle groups: wall squats, wall push-ups, forward lunges, reverse arm flexion/extension and supported heel raises. Each exercise is performed for two sets of 6-8 repetitions, with 1 minute of rest between sets. One session is supervised in person and two are remotely supervised at home each week. Exercise intensity and technique are adjusted for tolerance and safety. Participants switch to standard-duration modified Yijinjing after the 6-month assessment.
• Dietary Counseling and Health Education (Behavioral): Provided to all treatment pathways. Dietary advice targets total daily protein intake of 1.2-1.5 g/kg through ordinary food, using the lower of ideal or actual body weight. The study does not supply protein supplements. Three-day food diaries, including two weekdays and one non-working day, are reviewed at baseline, 6 months and 12 months with individualized advice. Standardized health education is delivered weekly for the first three weeks, approximately 30 minutes plus 5-10 minutes of questions per session, covering sarcopenia, nutrition, exercise safety and health management. Content and contact time are identical across groups.

Primary outcomes

• Change From Baseline in Short Physical Performance Battery Total Score at 6 Months [Baseline and 6 months]: The Short Physical Performance Battery (SPPB) assesses standing balance, 4-meter walking performance and five repeated chair stands. Total scores range from 0 to 12; higher scores indicate better physical performance. The primary endpoint is the 6-month total score minus the baseline total score. Noninferiority is concluded if the lower bound of the 95% confidence interval for the difference in change (Yijinjing minus resistance training) exceeds -0.5 points.

Secondary outcomes

• Appendicular Skeletal Muscle Mass Index [Baseline, 6 months and 12 months]: Appendicular skeletal muscle mass measured by multifrequency bioelectrical impedance analysis divided by height squared, expressed in kg/m².
• Handgrip Strength [Baseline, 6 months and 12 months]: Maximum dominant-hand grip strength from two dynamometer measurements, expressed in kg.
• Usual Walking Performance Over 6 Meters [Baseline, 6 months and 12 months]: Time required to walk 6 meters at usual pace, averaged over two trials.
• Five-Repetition Chair Stand Performance [Baseline, 6 months and 12 months]: Performance on five repeated chair stands as a measure of lower-limb function.
• Change From Baseline in SPPB Total Score at 12 Months [Baseline and 12 months]: The 12-month Short Physical Performance Battery total score minus baseline score. Scores range from 0 to 12, with higher scores indicating better physical performance.
• SF-36 Health-Related Quality of Life [Baseline, 6 months and 12 months]: The SF-36 assesses eight domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional health and mental health. Higher scores indicate better health-related quality of life.
• Fried Frailty Phenotype [Baseline, 6 months and 12 months.]: Frailty is assessed using the Fried Frailty Phenotype, which includes five criteria: unintentional weight loss, slow walking speed, low handgrip strength, low physical activity, and exhaustion. Each criterion is scored as 0 (absent) or 1 (present), yielding a total score ranging from 0 to 5. Higher scores indicate greater frailty and a worse outcome. A score of 0 indicates non-frailty, 1-2 indicates pre-frailty, and 3-5 indicates frailty.
• Montreal Cognitive Assessment [Baseline, 6 months and 12 months]: Cognitive function is assessed using the Montreal Cognitive Assessment. The total score ranges from 0 to 30. Higher scores indicate better cognitive function and a better outcome. When applicable, the education adjustment is applied according to the instrument's scoring instructions, with the adjusted total score capped at 30.
• Hamilton Depression Rating Scale [Baseline, 6 months and 12 months]: Depressive symptom severity is assessed using the 24-item Hamilton Depression Rating Scale. The total score is the sum of 24 item scores and ranges from 0 to 76. Higher scores indicate more severe depressive symptoms and a worse outcome.
• Hamilton Anxiety Rating Scale [Baseline, 6 months and 12 months]: Anxiety symptom severity is assessed using the 14-item Hamilton Anxiety Rating Scale. Each item is rated from 0 to 4, yielding a total score ranging from 0 to 56. Higher scores indicate more severe anxiety symptoms and a worse outcome.
• Adverse Event Incidence [Throughout the 12-month intervention]: Adverse events including falls, muscle strains and joint injuries are recorded throughout the intervention, including timing, severity, management and relationship to the intervention.
• Lumbar Spine Bone Mineral Density [Baseline, 6 months and 12 months]: DXA measurement of lumbar spine L1-L4 bone mineral density, collected only for participants enrolled at the two lead institutions.
• Femoral Neck Bone Mineral Density [Baseline, 6 months and 12 months]: DXA measurement of femoral neck bone mineral density, collected only for participants enrolled at the two lead institutions.
• Total Hip Bone Mineral Density [Baseline, 6 months and 12 months]: DXA measurement of total hip bone mineral density, collected only for participants enrolled at the two lead institutions.
• Irisin [Baseline, 6 months and 12 months]: Circulating Irisin measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Brain-Derived Neurotrophic Factor (BDNF) [Baseline, 6 months and 12 months]: Circulating Brain-Derived Neurotrophic Factor (BDNF) measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Myostatin [Baseline, 6 months and 12 months]: Circulating Myostatin measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Follistatin [Baseline, 6 months and 12 months]: Circulating Follistatin measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Follistatin-to-Myostatin Ratio [Baseline, 6 months and 12 months]: Ratio calculated from measured follistatin and myostatin concentrations as an exploratory mechanistic endpoint.
• Insulin-Like Growth Factor 1 (IGF-1) [Baseline, 6 months and 12 months]: Circulating Insulin-Like Growth Factor 1 (IGF-1) measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) [Baseline, 6 months and 12 months]: Circulating Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Basal Growth Hormone [Baseline, 6 months and 12 months]: Circulating Basal Growth Hormone measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest. Single basal growth hormone measurements are used only as an auxiliary indicator because secretion is pulsatile.
• Adrenocorticotropic Hormone (ACTH) [Baseline, 6 months and 12 months]: Circulating Adrenocorticotropic Hormone (ACTH) measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.
• Cortisol [Baseline, 6 months and 12 months]: Circulating Cortisol measured from morning fasting blood samples for exploratory mechanistic analysis. Sampling is performed at 07:00-09:00 after an 8-12-hour fast, at least 48 hours after the last exercise session and after 20 minutes of seated rest.

Sex: All, ages: 50 Years to any

Inclusion Criteria:

* Adults aged 50 years or older, of either sex.
* Confirmed sarcopenia with both low muscle mass and low handgrip strength according to the protocol. For ages 50-64: ASMI <7.6 kg/m² in men or <5.7 kg/m² in women, and grip strength <34 kg in men or <20 kg in women. For ages 65 or older: ASMI <7.0 kg/m² in men or <5.7 kg/m² in women, and grip strength <28 kg in men or <18 kg in women. ASMI is appendicular skeletal muscle mass measured by multifrequency bioelectrical impedance analysis divided by height squared.
* Clinically stable, with no acute illness, infection, major surgery or hospitalization within the preceding 4 weeks.
* Physician assessment confirms ability to tolerate moderate-intensity exercise and safely undertake Yijinjing and resistance training.
* Adequate cognitive function to cooperate with training, assessments and follow-up.
* Voluntary written informed consent.

Exclusion Criteria:

* Severe cardiopulmonary disease, including unstable angina, myocardial infarction within the preceding 3 months, severe heart failure or severe ventilatory impairment.
* Severe hepatic, renal or endocrine disease, including cirrhosis, renal failure, uncontrolled diabetes or severe thyroid dysfunction.
* Parkinson disease, residual deficits after stroke, severe joint deformity or persistent back or leg pain preventing completion of the prescribed exercise.
* Severe cognitive decline, Alzheimer disease, uncontrolled psychiatric illness or severe depression preventing adequate cooperation.
* Active malignancy or cachexia, or current anticancer treatment.
* Participation in another sarcopenia intervention trial within the preceding 3 months.
* Long-term use of glucocorticoids, anabolic hormones or other medicines affecting muscle metabolism.
* Unstable nutritional status, including weight fluctuation greater than 5% within the preceding month or dependence on parenteral nutrition.
* Severe osteoporosis with T-score <= -3.5 or fracture within the preceding 6 months creating a high exercise risk.
* Other exercise safety concerns or inability to complete study procedures as determined by the investigator.

• Yuchao Liu, Principal investigator, Beijing Hospital of Traditional Chinese Medicine
• Wei Tian, Principal investigator, Beijing Jishuitan Hospital