Aerobic exercise activates SLC7A11/GPx4 pathway to inhibit mitochondrial ferroptosis and prevent sarco-penia in aging mice
10.3969/j.issn.1001-1242.2025.04.004
- VernacularTitle:有氧运动激活SLC7A11/GPx4通路抑制线粒体铁死亡预防老年小鼠肌少症的作用
- Author:
Haitao WANG
1
;
Wenqian YANG
1
;
Yuqian LIU
1
Author Information
1. 岭南师范学院运动与健康研究所,广东省湛江市,524048;岭南师范学院体育科学学院
- Publication Type:Journal Article
- Keywords:
ferroptosis;
sarcopenia;
mitochondria;
aerobic exercise
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(4):501-507
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To elucidate the role of solute carrier protein 7,family member 11(SLC7A11)/Glutathione peroxi-dase 4(glutathione peroxidase 4,GPx4)regulated ferroptosis pathway in the improvement of sarcopenia through aerobic exercise,and to identify a new target for the prevention and treatment of sarcopenia with exercise.Method:Twenty 52-week-old Specific pathogen Free(SPF)C57BL/6 male mice were randomly divided into the old control group(OC)and the old exercise group(OE).There were 10 mice in each group.Following one week of adaptive exercise,moderate-intensity exercise with incremental load was implemented as follows:14 m/min at 1-2 weeks,15 m/min at 3-4 weeks,16m/min at 5-10weeks,17m/min at 11-16weeks,60min/d,all with a slope of 0°.Gastrocnemius was harvested for ultrathin electron microscope sections.The levels of Glutathione(GSH),muscle glycogen and non-heme iron(non-heme iron)were measured by spectro-photometer.The serum ferritin(SF),mitochondrial 8-hydroxy-2 deoxyguanosine(8-OHdG)and 4-Hydroxynone-na(4-HNE)were measured by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of iron metabolism-related proteins,such as GPx4,SLC7A11,ferroportin 1(FPN1)and ferri-tin heavy chain 1(FTH1)in gastrocnemius muscle.Result:①Compared with OC,the wet weights of quadriceps femoris and gastrocnemius in OE were signifi-cantly increased(P＜0.01).In the exercise group,mitochondrial cristae arranged neatly and densely,and the light and dark bands of myofilaments were clear.In the aged control group,the mitochondrial cristae of gas-trocnemius muscle were disrupted,vacuolated or pyknotic,showing typical features of ferroptosis.② The SF and the iron content of gastrocnemius muscle were decreased in OE(P＜0.01).③ The levels of 4-HNE and 8-OHdG in gastrocnemius muscle of OE were significantly lower than those of OC(P＜0.01).The GSH content in gastrocnemius of OE was significantly higher than that of OC(P＜0.01).④ The expressions of SLC7A11,GPx4,FPN1 and FTH1 in gastrocnemius muscle of OE were significantly higher than those of OC(P＜0.01).Conclusion:Moderate aerobic exercise can prevent age-related sarcopenia by activating the SLC7A11/GPx4 pathway and inhibiting mitochondrial ferroptosis.
