Morphological and Functional Biomarkers of Skeletal Muscle Adaptations in Sarcopenia

Lower-limb muscle function will be assessed using the 30-second Chair Stand Test. Participants will be asked to complete as many sit-to-stand repetitions as possible within 30 seconds using a standardized protocol. The outcome will be expressed as the number of complete repetitions. The primary analysis will evaluate changes from baseline to Week 12 and Week 48 between the exercise intervention and control groups.

Maximal handgrip strength will be assessed using a handgrip dynamometer according to a standardized protocol. The outcome will be expressed in kilograms or Newtons, according to the device output. Changes from baseline to Week 12 and Week 48 will be compared between groups.

Explosive strength and rapid force production will be assessed during lower-limb contractions using standardized dynamometric procedures. The outcome will quantify the ability to rapidly generate force and will be used to characterize neuromuscular adaptations to the intervention.

Functional walking capacity will be assessed using the 6-Minute Walk Test. Participants will be instructed to walk as far as possible in 6 minutes according to a standardized protocol. The outcome will be expressed as distance walked in meters.

Balance performance will be assessed using the Mini-Balance Evaluation Systems Test. The total score ranges from 0 to 28 points, with higher scores indicating better balance performance. Changes from baseline to Week 12 and Week 48 will be evaluated to assess intervention-related effects on balance.

Baseline, Week 12, and Week 48

Lean mass will be assessed using bioelectrical impedance analysis according to standardized procedures. The outcome will be expressed in percentage. Changes from baseline to Week 12 and Week 48 will be evaluated.

Skeletal muscle mass index will be assessed using bioelectrical impedance analysis according to standardized procedures. The outcome will be expressed as kilograms per square meter. Changes from baseline to Week 12 and Week 48 will be evaluated.

Appendicular skeletal muscle mass index will be assessed using dual-energy X-ray absorptiometry. The index will be calculated as appendicular skeletal muscle mass divided by height squared and expressed in kilograms per square meter. This is a continuous body composition parameter, not a scale score; therefore, no fixed minimum or maximum values apply. Higher values indicate greater appendicular skeletal muscle mass relative to height.

Quantitative ultrasound radio-frequency analysis will be used to assess muscle quality and microstructure. The primary QUS-RF parameter will be muscle echo-intensity, derived from standardized ultrasound acquisitions of selected lower-limb muscles. The outcome will be expressed in arbitrary units or grayscale units, according to the image analysis output. Changes from baseline to Week 12 and Week 48 will be evaluated and related to functional outcomes.

The diagnostic performance of quantitative ultrasound radio-frequency-derived muscle parameters for classifying sarcopenia status will be evaluated against reference criteria based on muscle mass and muscle strength. Diagnostic accuracy will be expressed as the area under the receiver operating characteristic curve. The area under the receiver operating characteristic curve ranges from 0.5 to 1.0 for a clinically useful classifier, with higher values indicating better diagnostic accuracy.

Health-related physical quality of life will be assessed using the 12-Item Short Form Health Survey Physical Component Summary score. The score ranges from 0 to 100, with higher scores indicating better physical health-related quality of life. Changes from baseline to Week 12 and Week 48 will be evaluated between groups.

Health-related mental quality of life will be assessed using the 12-Item Short Form Health Survey Mental Component Summary score. The score ranges from 0 to 100, with higher scores indicating better mental health-related quality of life. Changes from baseline to Week 12 and Week 48 will be evaluated between groups.

Mood state will be assessed using the Profile of Mood States questionnaire. The Total Mood Disturbance score will be calculated according to standard scoring procedures. Higher scores indicate greater mood disturbance and therefore a worse mood-related outcome. Changes from baseline to Week 12 and Week 48 will be evaluated between groups.

Systemic inflammation will be assessed by measuring serum C-reactive protein concentration. The outcome will be expressed in milligrams per liter. Changes from baseline to Week 48 will be evaluated between groups.