Age-dependent effects of aerobic training on cardiac expression of Akt1, mTOR, and CITED4 in immature, young-adult, and middle-aged rat myocardium

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.