Low- vs high-load power training on muscle quality, functional performance, and multi-omic profiles in frail older adults: protocol for the FrailPow randomized controlled trial

Background: Age-related frailty represents a growing global public health challenge, as it is associated with increased risk of falls, disability, and mortality, directly impacting functional decline and quality of life in older adults. Although resistance training is widely recommended as a therapeutic strategy, evidence on the differential effects of power training, particularly low- versus high-load modalities, compared with conventional programs remains limited. Integration of multi-omics biomarkers and advanced muscle quality assessments could enable the development of more personalized and effective exercise interventions for this population. Methods: This study will be a three-arm, multicenter, randomized controlled trial. A total of 207 older adults (≥ 70 years) meeting frailty criteria will be recruited from the Osakidetza healthcare network (Basque Country, Spain). Participants will be randomly assigned to: (1) low-load power training, (2) high-load power training, or (3) traditional resistance training. Each intervention will consist of a 12-week personalized exercise program. Assessments will be conducted at baseline, post-intervention, and at 24- and 36-weeks follow-up assessments. Measures will include muscle quality, functional performance, body composition, and multi-omics biomarkers. Results: This manuscript reports the protocol of the FrailPow randomized controlled trial; therefore, no outcome data are available at the time of submission. The study will quantify longitudinal changes across predefined assessment time points in muscle-related outcomes, functional performance, body composition, and multi-omics biomarkers. Conclusion: FrailPow will generate robust evidence on the efficacy and safety of power training in frail older adults, distinguishing the effects of load intensity. Additionally, the study will explore the potential of multi-omics biomarkers and advanced muscle quality metrics as tools to monitor and personalize interventions. Findings will be transferable to clinical and community settings, supporting precision exercise strategies within the Basque public health system to promote healthy aging. Trial registration: Registered on the Open Science Framework platform: https://osf.io/yrz4h/overview?view_only=802a2e066c1a4c85bc43d0d4ceb3b494 . Keywords: Frailty, muscle quality, power training, functional performance, multi-omics, gut microbiota