Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control
Exercise training is one of the most effective interventional strategies for sarcopenia in aged people. Nevertheless, the underlying mechanisms are not well recognized. Increasing studies have reported abnormal regulation of autophagy in aged skeletal muscle. Our current study aims to explore the ef...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2020-11-01
|
Series: | Frontiers in Physiology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.583478/full |
id |
doaj-4561c3c53ab446ef9c35681f10324c4c |
---|---|
record_format |
Article |
spelling |
doaj-4561c3c53ab446ef9c35681f10324c4c2020-11-25T03:08:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-11-011110.3389/fphys.2020.583478583478Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality ControlZhengzhong Zeng0Zhengzhong Zeng1Jiling Liang2Liangwen Wu3Hu Zhang4Jun Lv5Ning Chen6Graduate School, Wuhan Sports University, Wuhan, ChinaSports Institute, Chongqing University of Arts and Sciences, Chongqing, ChinaGraduate School, Wuhan Sports University, Wuhan, ChinaTianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Exercise Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, ChinaGraduate School, Wuhan Sports University, Wuhan, ChinaGraduate School, Wuhan Sports University, Wuhan, ChinaTianjiu Research and Development Center for Exercise Nutrition and Foods, Hubei Key Laboratory of Exercise Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, ChinaExercise training is one of the most effective interventional strategies for sarcopenia in aged people. Nevertheless, the underlying mechanisms are not well recognized. Increasing studies have reported abnormal regulation of autophagy in aged skeletal muscle. Our current study aims to explore the efficiency of exercise interventions, including treadmill exercise, resistance exercise, alternating exercise with treadmill running and resistance exercise, and voluntary wheel running, on 21-month-old rats with sarcopenia and to detect the underlying mechanisms. Results showed the declined mass of gastrocnemius muscle with deficient autophagy and excessive apoptosis as a result of up-regulated Atrogin-1 and MuRF1, declined Beclin1 level and LC3-II/LC3-I ratio, accumulated p62, increased Bax, and reduced Bcl-2 levels, and also exhibited a defective mitochondrial quality control due to declined PGC-1α, Mfn2, Drp1, and PINK1 levels. However, 12-week exercise interventions suppressed the decline in mass loss of skeletal muscle, accompanied by down-regulated Atrogin-1 and MuRF1, increased Beclin1 level, improved LC3-II/LC3-I ratio, declined p62 level, and reduced Bax and increased Bcl-2 level, as well as enhanced mitochondrial function due to the increased PGC-1α, Mfn2, Drp1, and PINK1 levels. Moreover, exercise interventions also down-regulated the phosphorylation of Akt, mTOR, and FoxO3a, and up-regulated phosphorylated AMPK to regulate the functional status of autophagy and mitochondrial quality control. Therefore, exercise-induced autophagy is beneficial for remedying sarcopenia by modulating Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control, and resistance exercise exhibits the best interventional efficiency.https://www.frontiersin.org/articles/10.3389/fphys.2020.583478/fullsarcopeniaexercise interventionautophagyAkt/mTOR signal pathwayAkt/FoxO3a signal pathwaymitochondrial quality control |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhengzhong Zeng Zhengzhong Zeng Jiling Liang Liangwen Wu Hu Zhang Jun Lv Ning Chen |
spellingShingle |
Zhengzhong Zeng Zhengzhong Zeng Jiling Liang Liangwen Wu Hu Zhang Jun Lv Ning Chen Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control Frontiers in Physiology sarcopenia exercise intervention autophagy Akt/mTOR signal pathway Akt/FoxO3a signal pathway mitochondrial quality control |
author_facet |
Zhengzhong Zeng Zhengzhong Zeng Jiling Liang Liangwen Wu Hu Zhang Jun Lv Ning Chen |
author_sort |
Zhengzhong Zeng |
title |
Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control |
title_short |
Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control |
title_full |
Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control |
title_fullStr |
Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control |
title_full_unstemmed |
Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control |
title_sort |
exercise-induced autophagy suppresses sarcopenia through akt/mtor and akt/foxo3a signal pathways and ampk-mediated mitochondrial quality control |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-11-01 |
description |
Exercise training is one of the most effective interventional strategies for sarcopenia in aged people. Nevertheless, the underlying mechanisms are not well recognized. Increasing studies have reported abnormal regulation of autophagy in aged skeletal muscle. Our current study aims to explore the efficiency of exercise interventions, including treadmill exercise, resistance exercise, alternating exercise with treadmill running and resistance exercise, and voluntary wheel running, on 21-month-old rats with sarcopenia and to detect the underlying mechanisms. Results showed the declined mass of gastrocnemius muscle with deficient autophagy and excessive apoptosis as a result of up-regulated Atrogin-1 and MuRF1, declined Beclin1 level and LC3-II/LC3-I ratio, accumulated p62, increased Bax, and reduced Bcl-2 levels, and also exhibited a defective mitochondrial quality control due to declined PGC-1α, Mfn2, Drp1, and PINK1 levels. However, 12-week exercise interventions suppressed the decline in mass loss of skeletal muscle, accompanied by down-regulated Atrogin-1 and MuRF1, increased Beclin1 level, improved LC3-II/LC3-I ratio, declined p62 level, and reduced Bax and increased Bcl-2 level, as well as enhanced mitochondrial function due to the increased PGC-1α, Mfn2, Drp1, and PINK1 levels. Moreover, exercise interventions also down-regulated the phosphorylation of Akt, mTOR, and FoxO3a, and up-regulated phosphorylated AMPK to regulate the functional status of autophagy and mitochondrial quality control. Therefore, exercise-induced autophagy is beneficial for remedying sarcopenia by modulating Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control, and resistance exercise exhibits the best interventional efficiency. |
topic |
sarcopenia exercise intervention autophagy Akt/mTOR signal pathway Akt/FoxO3a signal pathway mitochondrial quality control |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2020.583478/full |
work_keys_str_mv |
AT zhengzhongzeng exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT zhengzhongzeng exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT jilingliang exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT liangwenwu exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT huzhang exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT junlv exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol AT ningchen exerciseinducedautophagysuppressessarcopeniathroughaktmtorandaktfoxo3asignalpathwaysandampkmediatedmitochondrialqualitycontrol |
_version_ |
1724666846213308416 |