Frailty, Physical Performance, and Molecular Changes in Older Adults Participating in Different Exercise Programs: A 12-Week Preference-Based Non-Randomized Study

Background: Multidimensional evidence on exercise participation and frailty in older adults is limited. Methods: This 12-week preference-based, non-randomized study included 145 participants (mean age 82.25 years): walking (n = 50), resistance training (n = 20), Traditional Chinese exercise (n = 23), and control (n = 52). Frailty was the primary outcome; physical-performance and molecular analyses were exploratory. Paired trajectories, baseline-stratified binary transitions, and adjusted associations were examined. Results: Among paired participants, pre-frailty/frailty prevalence changed from 70.0% to 60.0% with walking, 90.0% to 70.0% with resistance training, 50.0% to 63.6% with Traditional Chinese exercise (n = 22), and 50.0% to 69.2% in controls. Baseline status constrained opportunities for binary improvement or deterioration. All adjusted frailty risk-ratio confidence intervals included 1. Walking was associated with faster Timed Up and Go and Five-Yard Walk Test performance after correction across eight outcomes. Molecular changes also occurred in controls; intervention timing and potential laboratory-batch confounding limited between-group interpretation. No microbiome taxon survived multiplicity correction; small paired samples limited precision. Conclusions: Walking and resistance-training groups showed descriptively more favorable prevalence trajectories, but adjusted frailty comparisons remained inconclusive. These findings do not establish frailty prevention, modality superiority, or exercise-specific molecular mechanisms.