4.3 Article

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal

Journal

ONCOTARGET
Volume 8, Issue 11, Pages 17475-17490

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15420

Keywords

D-galactose; spermindine; exercise; autophagy; AMPK-FOXO3a signal pathway; Gerotarget

Funding

  1. National Natural Science Foundation of China [31571228]
  2. Foundation of Research Project from General Administration of Sport of China [2014B093]
  3. Chutian Scholar Program
  4. Hubei Superior Discipline Groups of Physical Education and Health Promotion
  5. Outstanding Youth Scientific and Technological Innovation Team from Education Department of Hubei Province [T201624]
  6. Innovative Start-Up Foundation from Wuhan Sports University to Ning Chen
  7. Natural Science Foundation of Hubei Province [2016CFB342]
  8. China Postdoctoral Science Foundation [2015M582292]

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The quality control of skeletal muscle is a continuous requirement throughout the lifetime, although its functions and quality present as a declining trend during aging process. Dysfunctional or deficient autophagy and excessive apoptosis may contribute to the atrophy of senescent skeletal muscle. Spermidine, as a natural polyamine, can be involved in important cellular functions for lifespan extension and stress resistance in several model organisms through activating autophagy. Similarly, cellular autophagic responses to exercise have also been extensively investigated. In the present study, in order to confirm the mitigation or amelioration of skeletal muscle atrophy in aging rats through spermidine coupled with exercise intervention and explore corresponding mechanisms, the rat model with aging-related atrophy of skeletal muscle was established by intraperitoneal injection of D-galactose (D-gal) (200 mg/ kg(.)d ), and model rats were subjected to the intervention with spermidine (5 mg/kg(.)d ) or swimming (60 min/d, 5 d/wk) or combination for 42 days. Spermidine coupled with exercise could attenuate D-gal-induced aging-related atrophy of skeletal muscle through induced autophagy and reduced apoptosis with characteristics of more autophagosomes, activated mitophagy, enhanced mitochondrial quality, alleviated cell shrinkage, and less swollen mitochondria under transmission scanning microscopic observation. Meanwhile, spermidine coupled with exercise could induce autophagy through activating AMPK-FOXO3a signal pathway with characterization of increased Beclin1 and LC3-II/LC3-I ratio, up-regulated anti-apoptotic Bcl-2, down-regulated pro-apoptotic Bax and caspase-3, as well as activated AMPK and FOXO3a. Therefore, spermidine combined with exercise can execute the prevention or treatment of D-galinduced aging-related skeletal muscle atrophy through enhanced autophagy and reduced apoptosis mediated by AMPK-FOXO3a signal pathway.

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