Cardiovascular disease (CVD) has been a leading cause of death globally, with a significant impact on healthy aging. Aging is significantly rising globally, and older adults are at increased risk of age-related arrhythmias, and the mechanisms underlying age-related arrhythmias remain unclear. In this study, we investigated the relationship between ANK2 and age-related arrhythmias in aged Drosophila and how endurance exercise modulates ANK2 expression on age-related arrhythmias. Method: Wild type w1118 female virgin flies were examined at 10 days of age (10C, young), 30 days of age (30C, middle-aged), and 50 days of age (50C, old) to assess age-related arrhythmias and ANK2 expression. The assays included Drosophila cardiac function analysis, including heart rate (HR), cardiac cycle (HP), and arrhythmia index (AI) to quantify the occurrence of arrhythmias he relative expression level of ANK2 mRNA was detected by RT-qPCR; furthermore, virgin flies of the UAS-ANK2RNAi strain were crossed with the wild-type W1118 strain using UAS-ANK2RNAi, respectively, and the F1 generation virgin flies obtained were divided into ANK2 knockdown (KD) group. The third generation Drosophila locomotor device was used to perform endurance exercise intervention for the aged and knockdown groups, which were recorded as 50E and KDE groups. The locomotion group underwent locomotion intervention at 38 days of age for a fortnight with two days of rest per week for 2.5 hours per day at 24s/r. 1) Compared to the 10C group, the 30C and 50C groups had significantly lower HR, significantly higher HP, significantly higher AI, exhibited more prevalent arrhythmias as well as a significant decrease in the relative expression level of ANK2 mRNA in the 30C and 50C groups.2) Compared to the 50C group, the 50E group had significantly higher HR, significantly lower HP, significantly lower AI, a significant decrease in the incidence of arrhythmias as well as a significant decrease in the relative expression level of ANK2 mRNA. Compared with the KD group, the KDE group showed a significant increase in heart rate, a significant decrease in HP, a significant decrease in AI, a significant decrease in the incidence of arrhythmia, and a significant up-regulation of the relative expression level of ANK2 mRNA. Conclusion: The increase of age-related arrhythmias in Drosophila is associated with the expression of ANK2; moreover, endurance exercise ameliorates age-related arrhythmias by up regulating the expression of ANK2 in Drosophila
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