Creatine combined with exercise regulates skeletal muscle atrophy and mitophagy in rat models of sarcopenia

doi:10.16352/j.issn.1001-6325.2026.11.1513

Abstract

Abstract: Objective To investigate the regulatory effects of creatine supplementation combined with exercise on skeletal muscle atrophy and mitophagy in a rat model of sarcopenia. Methods Thirty rats were randomly divided into the control, model, creatine administration, exercise, and creatine plus exercise groups (n=6 per group). Except for the control group, all groups underwent bilateral ovariectomy combined with dexamethasone administration to establish a sarcopenia model. The creatine group received anhydrous creatine solution of 0.3 g/(kg·d) for 5 weeks; The exercise group underwent training for 5 weeks (3 sessions/week); And the creatine plus exercise group received both interventions. Parameters included the sarcopenia index (SI; wet skeletal muscle weight-to-bodyweight ratio), and protein expression was determined by Western blot. Results Compared with the control group, the model group exhibited a reduced SI value (P＜0.05), decreased cross-sectional area of muscle fibers (1 244 μm² vs. 2 156 μm², P＜0.05) and an increased proportion of centralized nuclei (28.67% vs. 12.43%, P＜0.05), down-regulated protein kinase B(AKT) expression, and up-regulated autophage related 12 gene(ATG12) expression (all P＜0.05).Compared to model group, the creatine, exercise group and creatine + exercise groups all demonstrated significant increases in SI values and muscle fiber cross-sectional areas (all P＜0.05) and centralized nuclei proportion (all P＜0.05). The creatine plus exercise group showed significantly higher SI values and cross-sectional areas of muscle fiber than either the creatine or exercise group alone (all P＜0.05). Moreover, ATG12 expression in the creatine plus exercise group was significantly down-regulated as compared to both the creatine and exercise groups (all P＜0.05). Conclusions Creatine supplementation combined with exercise alleviates skeletal muscle atrophy and mitigates mitophagy imbalance in a rat model of sarcopenia by synergistically up regulating the SI value, improving muscle fiber morphology, and modulating the expression of AKT, ATG12, Beclin1, and ULK1.

Key words: skeletal muscle atrophy, creatine, exercise, autophagy

CLC Number:

R685

Maojudan·AZATI, Jianaer·MOLEDABIEKE, BAI Rui, Maierdang·AILIMU. Creatine combined with exercise regulates skeletal muscle atrophy and mitophagy in rat models of sarcopenia[J]. Basic & Clinical Medicine, 2026, 46(11): 1513-1518.

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