Skuld (skd) is a subunit of the Mediator complex subunit complex. In the heart, skd controls systemic obesity, is involved in systemic energy metabolism, and is closely linked to cardiac function and aging. However, it is unclear whether the effect of cardiac skd on cardiac energy metabolism affects cardiac function. We found that cardiac-specific knockdown of skd showed impaired cardiac function, metabolic impairment, and premature aging. Drosophila was subjected to an exercise and high-fat diet (HFD) intervention to explore the effects of exercise on cardiac skd expression and cardiac function in HFD Drosophila. We found that Hand-Gal₄>skd RNAi (KC) Drosophila had impaired cardiac function, metabolic impairment, and premature aging. Regular exercise significantly improved cardiac function and metabolism and delayed aging in HFD KC Drosophila. Thus, our study found that the effect of skd on cardiac energy metabolism in the heart affected cardiac function. Exercise may counteract age-related cardiac dysfunction and metabolic disturbances caused by HFD and heart-specific knockdown of skd. Skd may be a potential therapeutic target for heart disease.

Sleep–wake stability is imbalanced with natural aging, and microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and aging; however, the biological functions of miRNAs in regulating aging-related sleep–wake behavior remain unexplored. This study varied the expression pattern of dmiR-283 in Drosophila and the result showed that the aging decline in sleep–wake behavior was caused by the accumulation of brain dmiR-283 expression, whereas the core clock genes cwo and Notch signaling pathway might be suppressed, which regulate the aging process. In addition, to identify exercise intervention programs of Drosophila that promote healthy aging, mir-283^SP/+ and Pdf > mir-283^SP flies were driven to perform endurance exercise for a duration of 3 weeks starting at 10 and 30 days, respectively. The results showed that exercise starting in youth leads to an enhanced amplitude of sleep–wake rhythms, stable periods, increased activity frequency upon awakening, and the suppression of aging brain dmiR-283 expression in mir-283^SP/+ middle-aged flies. Conversely, exercise performed when the brain dmiR-283 reached a certain accumulation level showed ineffective or negative effects. In conclusion, the accumulation of dmiR-283 expression in the brain induced an age-dependent decline in sleep–wake behavior. Endurance exercise commencing in youth counteracts the increase in dmiR-283 in the aging brain, which ameliorates the deterioration of sleep–wake behavior during aging.

Alteration of HIF‐1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF‐1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila , a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila . The hypoxic complex exercise promoted the whole‐body HIF‐1α expression in Drosophila , and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF‐1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF‐1α to enhance the exercise capacity and heart pumping function of Drosophila , and improved the quality of sleep.

Although studies have shown that myomesin 2 (MYOM2) mutations can lead to hypertrophic cardiomyopathy (HCM), a common cardiovascular disease that has a serious impact on human life, the effect of MYOM2 on cardiac function and lifespan in humans is unknown. In this study, dMnM (MYOM2 homologs) knockdown in cardiomyocytes resulted in diastolic cardiac defects (diastolic dysfunction and arrhythmias) and increased cardiac oxidative stress. Furthermore, the knockdown of dMnM in indirect flight muscle (IFM) reduced climbing ability and shortened lifespan. However, regular exercise significantly ameliorated diastolic cardiac dysfunction, arrhythmias, and oxidative stress triggered by dMnM knockdown in cardiac myocytes and also reversed the reduction in climbing ability and shortening of lifespan caused by dMnM knockdown in Drosophila IFM. In conclusion, these results suggest that Drosophila cardiomyocyte dMnM knockdown leads to cardiac functional defects, while dMnM knockdown in IFM affects climbing ability and lifespan. Furthermore, regular exercise effectively upregulates cardiomyocyte dMnM expression levels and ameliorates cardiac functional defects caused by Drosophila cardiomyocyte dMnM knockdown by increasing cardiac antioxidant capacity. Importantly, regular exercise ameliorates the shortened lifespan caused by dMnM knockdown in IFM.

MicroRNAs (miRNAs) are crucial in regulating cardiac aging and related diseases, yet few functional miRNAs have been identified. Prior studies showed miR-216a upregulation in heart failure patients, but its impact on aging hearts is unknown. Our study revealed systemic miR-283 overexpression or knockdown caused age-related bradycardia, mimicking human bradyarrhythmia. Importantly, we found that knockdown of miR-283 in ventral-lateral neurons (LN _v s), rather than in the heart, led to the occurrence of bradyarrhythmia, which was mainly caused by the upregulation of miR-283 expression in the whole brain and heart. The gene of clockwork orange ( cwo ) may mediate miR-283's effect on heart rhythm. Additionally, to investigate the miRNA regulatory mechanism underlying exercise-induced delay in cardiac aging, we conducted a three-week endurance exercise program on miR-283 knockdown flies in LN _v s. We found that exercise significantly downregulated the accumulation of miR-283 in the brain and myocardium caused by aging or miR-283 knockdown in LN _v s, improved the structure of myocardial fibers, and effectively reduced bradyarrhythmia. Our findings provides a new perspective on distal neuromodulation and intervention in cardiac aging.

Background: Some studies have shown that the stability and transcription of HIF-1Α significantly increases under hypoxic conditions, and HIF and its downstream targets are becoming a new choice for the treatment of various organ injuries to improve physical function. Combined with the team's pre-screening of suitable hypoxic compound exercise protocols, this study aimed to explore the link between the expression of exercise HIF-1Α under hypoxic conditions and cardiac function, in order to provide a realistic and theoretical basis for the improvement of cardiac function by hypoxic compound exercise. Methods: 300 Drosophila flies of wild-type W¹¹¹⁸⁸ strain feathered within 12 hours were collected and randomly divided into control (NC), hypoxic quiet (HC), normoxic exercise (NE), and intermittent hypoxic training (HE) groups, with 100 Drosophila in each group, and were subjected to intermittent hypoxic, normoxic and hypoxic combined exercise interventions for 5 consecutive days, lasting for one hour per day, at the age of 7 days, respectively. The gas used in both HC and HE groups was a mixture of 6% O2 and 94% N2. At 24 h after the intervention, the changes of cardiac actin were observed by F-actin staining, the changes of HIF-1Α expression level in the heart were detected by RT-qPCR, and 30 s of Drosophila heart beats were captured by an EM-CCD digital video camera (130 frames/s) to quantify the indexes of Drosophila cardiac pumping function. Results: Compared with the NC group, HIF-1Α expression increased in the heart after hypoxic compound exercise (P < 0.001), the diameter of the heart tube became larger, the arrangement of cardiac myofilaments was tighter and neater, the systolic diameter of the heart increased (P < 0.05), the diastolic diameter increased (P < 0.001), and the shortening fraction improved (P < 0.001). Compared with the NC group, HIF-1Α expression did not change significantly in the NE group, and the heart had an increased systolic diameter (P < 0.05), an increased diastolic diameter (P < 0.001), and a slightly improved shortening fraction. Compared with the NC group, after intermittent hypoxic exposure, cardiac HIF-1Α expression was elevated, the diameter of the heart became smaller, myocardial myofilaments were irregularly arranged, the systolic and diastolic diameters did not change significantly, and the shortening fraction was slightly increased. Conclusion: Hypoxic compound exercise promoted HIF-1Α expression in the heart and improved cardiac pumping function.