Circulating MiRNAs as biomarkers of gait speed responses to aerobic exercise training in obese older adults

Gait speed is a useful predictor of adverse outcomes, including incident mobility disability and mortality in older adults. While aerobic exercise training (AEX) is generally an effective therapy to improve gait speed, individual responses are highly variable. Circulating microRNAs (miRNAs) may contribute to inter-individual changes in gait speed with AEX. We examined whether plasma miRNAs are associated with gait speed changes (dGaitSp) in 33 obese older adults (age: 69.3±3.6 years, BMI: 34.0±3.1 kg/m 2 , 85% white, 73% women) who performed treadmill walking, 4 days/week for 5 months. Gait speed (baseline: 1.02±0.19 m/s; range of response: -0.2 to 0.35 m/s) was assessed using a 400 meter-fast-paced walk test. Using Nanostring technology, 120 out of 800 miRNAs were found to be abundantly expressed in plasma and 4 of these were significantly changed after AEX: miR-376a-5p increased, while miR-16-5p, miR-27a-3p, and miR-28-3p all decreased. In addition, baseline miR-181a-5p levels (r=-0.40, p=0.02) and percent changes in miR-92a-3p (r=-0.44, p=0.009) associated negatively with dGaitSp. Linear regression combined baseline miR-181a-5p and miR-92a-3p levels showed even stronger associations with dGaitSp (r=-0.48, p=0.005). These results suggest that circulating miR-181a-5p and miR-92a-3p may predict and/or regulate AEX-induced gait speed changes in obese older adults.