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Supervised Exercise Intervention Restores Physical Activity and MultiOMIC-Derived Frailty Biomarkers in Older Adults
Diego Marcos-Perez1, Sara Cruces-Salguero1, Morelva Saeteros1,2
1Cellular Oncology Group, Biogipuzkoa (Biodonostia) Health Research Institute, San Sebastian, Spain.
Journal of Cachexia, Sarcopenia and Muscle
|August 9, 2026
Summary
Physical exercise interventions can reverse biological frailty in older adults by altering key molecular biomarkers. Specific biomarkers, including miR454, EGR1, and DDX11L1, effectively predict response to exercise, offering new outcome measures for frailty research.
Area of Science:
- Gerontology and Exercise Science
- Molecular Biology and Biomarkers
- Personalized Medicine
Background:
- Frailty mechanisms are actively researched, with studies identifying molecular signatures in frail individuals.
- Previous research highlighted specific biomarkers from FRAILOMIC and BIOFRAIL studies associated with frailty.
- The impact of physical exercise interventions on these molecular frailty signatures remained unexplored.
Purpose of the Study:
- To investigate the expression of FRAILOMIC and BIOFRAIL molecular biomarkers following a personalized exercise intervention in older adults.
- To assess the effectiveness of a multicomponent physical exercise program on functional capacity and frailty status.
- To identify biomarkers predictive of response to exercise interventions in older individuals.
Main Methods:
- A 16-week multicomponent physical exercise program was administered to an intervention group (n=44) compared to a control group (n=24).
- Clinical, functional, and frailty assessments were conducted pre- and post-intervention.
- Molecular biomarkers were quantified using qRT-PCR and ELISA; latent class analysis identified responders and non-responders.
Main Results:
- The exercise group showed significant improvements in functional capacity (SPPB, grip strength, gait speed) and reduced frailty criteria.
- Expression of multiple FRAILOMIC (e.g., miR125b, RAGE) and BIOFRAIL (e.g., EGR1, miR454) biomarkers reversed significantly post-exercise.
- miR454, EGR1, DDX11L1, and Troponin demonstrated strong predictive value for distinguishing exercise responders from non-responders.
Conclusions:
- Multicomponent exercise interventions effectively improve functional status and reverse molecular markers of biological frailty in older adults.
- The BIOFRAIL biomarkers miR454, EGR1, and DDX11L1 are potent predictors of exercise intervention response, with an AUC of 0.83.
- OMIC-derived frailty biomarkers serve as valuable outcome measures for evaluating the efficacy of interventions in aging populations.
