Research Paper Volume 13, Issue 15 pp 19542—19560

Physical exercise prevents age-related heart dysfunction induced by high-salt intake and heart salt-specific overexpression in Drosophila

Deng-Tai Wen1,2, , Lan Zheng1, , Kai Lu1, , Wen-Qi Hou2, ,

  • 1 Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, Hunan Normal University, Changsha 410012, Hunan Province, China
  • 2 Ludong University, Yantai 264025, Shandong Province, China

Received: December 21, 2020       Accepted: July 17, 2021       Published: August 12, 2021
How to Cite

Copyright: © 2021 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


A long-term high-salt intake (HSI) seems to accelerate cardiac aging and age-related diseases, but the molecular mechanism is still not entirely clear. Exercise is an effective way to delay cardiac aging. However, it remains unclear whether long-term exercise (LTE) can protect heart from aging induced by high-salt stress. In this study, heart CG2196(salt) specific overexpression (HSSO) and RNAi (HSSR) was constructed by using the UAS/hand-Gal4 system in Drosophila. Flies were given exercise and a high-salt diet intervention from 1 to 5 weeks of age. Results showed that HSSR and LTE remarkably prevented heart from accelerated age-related defects caused by HSI and HSSO, and these defects included a marked increase in heart period, arrhythmia index, malondialdehyde (MDA) level, salt expression, and dTOR expression, and a marked decrease in fractional shortening, SOD activity level, dFOXO expression, PGC-1α expression, and the number of mitochondria and myofibrils. The combination of HSSR and LTE could better protect the aging heart from the damage of HSI. Therefore, current evidences suggested that LTE resisted HSI-induced heart presenility via blocking CG2196(salt)/TOR/oxidative stress and activating dFOXO/PGC-1α. LTE also reversed heart presenility induced by cardiac-salt overexpression via activating dFOXO/PGC-1α and blocking TOR/oxidative stress.


HSI: High-salt intake; LTE: Long-term exercise; E: Exercise; ET: Exercise training; MDA: Malondialdehyde; TOR: Target of rapamycin; SOD: Superoxide dismutase; FOXO/ Foxo: Forkhead transcription factor; PGC-1α/ PGC-1/srl: Peroxisome proliferator-activated receptor-γcoactivator -1α; CR: Calorie restriction; ROS: Reactive oxygen species; HSSR: Heart CG2196(salt) specific RNAi; HSSO: Heart CG2196(salt) specific overexpression; HFD: High-fat diet; PI3K: Phosphatidylinositol-3-kinase; Akt: Protein kinase B; Sir2: Silent Information Regulator 2; HF: Heart failure; LV: Left ventricular; Post-MI: Post-myocardial infarction; Salt-OE: Salt-overexpression.