Sustainability of exercise-induced benefits on circulating MicroRNAs and physical fitness in community-dwelling older adults: a randomized controlled trial with follow up

Abstract

Background: Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes.

Methods: This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA).

Results: Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength.

Conclusion: An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.

Keywords: Aerobic exercise; Body composition; Pathway analysis; Physical fitness.

Fig. 1

Flow Diagram of Selected Participants. ACSM, American College of Sports Medicine; COPD, chronic obstructive pulmonary disease; DJD, degenerative joint disorder; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; F/M, female/male; MI, myocardial infarction; MICT. moderate-intensity continuous training; MMSE, mini-mental status examination; stp/d, step per day; WS, walking speed

Fig. 2

A normalized body fat mass (nBFM) representing relative fat amount in SET participants significantly decreased during follow up and was significantly less than HET participants at the end of follow up. B normalized skeletal muscle mass (nSKM) representing relative skeletal muscle amount increased significantly after MICT, and EX participants had significantly greater nSKM than those in CON participant. C estimated metabolic equivalent (MET) significantly increased during follow up in EX participants. D calf circumference in CON participants representing muscle mass significantly decreased during follow up, and significantly less muscle mass than EX participants. E handgrip strength in CON participant significantly decreased during, and significantly less muscle mass than EX participants. F EX took significantly less time than CON participants to complete 5-time sit-to-stand test. *: significant group effect; ‡: significant time x group interaction by mixed ANOVA and Bonferroni post-hoc test to assess differences between each of the assessment time point

Fig. 3

A a non-significant increase of cmiR-21 was observed in EX participants and was greater than those in CON participants during follow up. B a significant increase of cmiR-126 in EX participants and was significantly greater than those in CON participants during follow up. C a significant increase of cmiR-146a was observed in EX participants and was greater than those in CON participants during follow up. D a significant increase of cmiR-222 in EX participants and was significantly greater than those in CON participants during follow up. *: significant group effect; ‡: significant time x group interaction by mixed ANOVA and Bonferroni post-hoc test to assess differences between each of the assessment time point

Fig. 4

Mean walking steps per day (stp/d) in a week representing the step amount in the week during follow-up

Fig. 5

Pathway Analysis for association between MICT and physical fitness. A significant direct effect of MICT to normalized body fat mass adjusted by c-miRNA-21. B significant direct effect of MICT to normalized skeletal muscle mass adjusted by c-miRNA-21. C significant m1 and m2 path, suggesting association between c-miRNA-21 and training/CRF. D significant m1 and m2 path, suggesting association between c-miRNA-21 and training/lower limbs strength. *: significant association