Case Report: Network Physiology Markers of Inter-muscular Interactions indicate Reversal of Age Decline with Exercise Training

Sergi Garcia-Retortillo^1,2,3Óscar Abenza Ortega^3,4Ladda Thiamwong¹Rui Xie¹Michelle Gordon⁵Plamen Ch. Ivanov^6,7,8*Tina E. Brinkley^9*

• ¹College of Nursing, University of Central Florida, Orlando, United States
• ²Department of Health and Exercise Science, Wake Forest University, Winston-Salem, Spain
• ³Complex Systems in Sport, INEFC University of Barcelona, Barcelona, Spain
• ⁴Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
• ⁵Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, United States
• ⁶Keck Laboratory for Network Physiology, Department of Physics, Boston University, Boston, United States
• ⁷Department of Neurosurgery, Boston University Chobanian & Avedisian School of Medicine, Boston, United States
• ⁸Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria
• ⁹Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest University School of Medicine, Winston-Salem, United States

Aging is associated with a decline in inter-muscular coordination and overall functional capacity. While the benefits of exercise on individual physiological systems are well established, it remains unclear whether regular training can also enhance inter-muscular network interactions and counteract age-related decline. Using a Network Physiology approach, this Case Report investigates the effects of a home-based exercise program on inter-muscular coordination in two older adults. Two older adults (aged 69 and 73) completed a 12-week program that included twice-weekly virtual group sessions, and one weekly session of moderate-intensity aerobic exercise (30 minutes). Before and after the intervention, participants underwent a maximal cardiopulmonary exercise test (CPET) on a motorized treadmill. During the CPET, surface electromyography (EMG) was recorded from the left and right rectus femoris and biceps femoris. Inter-muscular coordination was quantified using the Amplitude-Amplitude Cross-Frequency Coupling (ACFC) method. Ten time series of EMG band power were extracted for each muscle, representing distinct neuromuscular processes. Pearson's cross-correlation was then computed for each pair of EMG band power time series across all muscles. Pre-Intervention, both participants showed low overall link strength across all sub-networks. Post-Intervention, there was a pronounced (~400%) increase in average link strength across all sub-networks in both participants, primarily reflecting enhanced synchronization between distinct frequency bands across the rectus femoris and biceps femoris. These preliminary findings suggest that structured exercise may enhance inter-muscular network coordination in older adults. ACFC-derived network measures offer a promising tool for detecting early age-related decline and evaluating neuromuscular adaptations to exercise interventions.