European journal of applied physiology · 2026
Age-dependent effects of aerobic training on cardiac expression of Akt1, mTOR, and CITED4 in immature, young-adult, and middle-aged rat myocardium.
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Haji Asiabani Pouria, Ghasemnian Agha Ali, Karimi Asl Akram, Wong Alexei
Аннотация
PURPOSE: Cardiac plasticity declines with age; however, mechanisms underlying aerobic training (AT)-induced cardiac remodeling across developmental stages remain unclear. Exercise-induced hypertrophy is mediated by PI3K/Akt/mTOR signaling and its downstream effector CITED4, but whether these pathways respond uniformly across age is unknown. This study investigated age-dependent effects of AT on the Akt1/mTOR/CITED4 axis in rat myocardium.
METHODS: Forty-eight male Wistar rats were assigned to three age cohorts: immature (4-5 weeks), young-adult (18-20 weeks) and middle-aged (41-42 weeks). Animals were randomly allocated within each age stratum to either control or exercise groups (n = 8/group) and completed 8 weeks of running-wheel training. Ventricular Akt1, mTOR, and CITED4 mRNA expression was quantified by qRT-PCR. Relative expression was determined using the 2-ΔΔCt method, and statistics were performed on log₂-transformed 2-ΔCt values using two-way ANOVA.
RESULTS: AT elicited age-dependent transcriptional responses in myocardium. A significant Age × Exercise interaction was observed for Akt1 expression (p = 0.011), with post hoc analysis showing increased expression only in immature rats (p = 0.001). In contrast, mTOR expression increased with exercise regardless of age (main effect of Exercise, p < 0.001). CITED4 expression also showed a significant Age × Exercise interaction (p < 0.001), indicating differential responsiveness to aerobic training across developmental stages.
CONCLUSION: AT induces age-dependent cardiac adaptations. Akt1 upregulation was restricted to immature rats, whereas mTOR expression increased irrespective of age. CITED4 showed marked age-dependent responsiveness to training. These findings suggest that the immature myocardium exhibits greater transcriptional sensitivity to aerobic exercise than later developmental stages.
METHODS: Forty-eight male Wistar rats were assigned to three age cohorts: immature (4-5 weeks), young-adult (18-20 weeks) and middle-aged (41-42 weeks). Animals were randomly allocated within each age stratum to either control or exercise groups (n = 8/group) and completed 8 weeks of running-wheel training. Ventricular Akt1, mTOR, and CITED4 mRNA expression was quantified by qRT-PCR. Relative expression was determined using the 2-ΔΔCt method, and statistics were performed on log₂-transformed 2-ΔCt values using two-way ANOVA.
RESULTS: AT elicited age-dependent transcriptional responses in myocardium. A significant Age × Exercise interaction was observed for Akt1 expression (p = 0.011), with post hoc analysis showing increased expression only in immature rats (p = 0.001). In contrast, mTOR expression increased with exercise regardless of age (main effect of Exercise, p < 0.001). CITED4 expression also showed a significant Age × Exercise interaction (p < 0.001), indicating differential responsiveness to aerobic training across developmental stages.
CONCLUSION: AT induces age-dependent cardiac adaptations. Akt1 upregulation was restricted to immature rats, whereas mTOR expression increased irrespective of age. CITED4 showed marked age-dependent responsiveness to training. These findings suggest that the immature myocardium exhibits greater transcriptional sensitivity to aerobic exercise than later developmental stages.