Evidence map›Paper›PMID 40835003›Full record

ArticleJournal of advanced research2026

Exercise improves hypobaric hypoxia-induced skeletal muscle dysfunction via Sirt1-Mediated myotube and mitochondrial remodeling.

Caiyun Wang, Wu-Gui Chen, Honghong Chen, Jialin Zhao, Jintao He, Yajie Hu, Mengting He, Yuyu Zhang, Cheng-Shou Lin, Jun Chang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Caiyun WangPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Wu-Gui ChenDepartment of Orthopaedics, Fujian Medical University Affiliated Mindong Hospital, Fujian, China.
Honghong ChenPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Jialin ZhaoPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Jintao HePhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Yajie HuPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Mengting HePhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Yuyu ZhangPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China.
Cheng-Shou LinDepartment of Orthopaedics, Fujian Medical University Affiliated Mindong Hospital, Fujian, China. Electronic address: lcsmindong@fjmu.edu.cn.
Jun ChangPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China; Department of Orthopaedics, Fujian Medical University Affiliated Mindong Hospital, Fujian, China. Electronic address: jchang@fudan.edu.cn.
Xinhua LiuPhenome Research Center of TCM, Department of Traditional Chinese Medicine, Shanghai Pudong Hospital, Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai, China; Department of Orthopaedics, Fujian Medical University Affiliated Mindong Hospital, Fujian, China. Electronic address: liuxinhua@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSkeletal muscle function is profoundly challenged under high-altitude environments, where hypobaric hypoxia disrupts structural integrity and impairs physiological function. However, few animal studies have examined the impact of hypobaric hypoxia on skeletal muscle and molecular basis. While exercise training holds promise for alleviating hypoxia-induced muscle dysfunction, the understanding of its protective mechanisms remains limited.

objectivesWe aimed to investigate chronic hypobaric hypoxia-induced myotube atrophy and mitochondrial dysfunction in mouse models and C2C12 cells, and develop a combined exercise strategy (preconditioning and hypoxic training) to mitigate hypoxia-related muscle pathology.

methodsA mouse chronic hypobaric hypoxia model (45-day exposure, 6,000 m equivalent) combined with in vitro C2C12 myotube hypoxia simulations was employed. Muscle atrophy, mitochondrial ultrastructure, and molecular pathways were analyzed via histology, proteomics, and functional assays. Exercise interventions included preconditioning (9-week treadmill training) followed by voluntary wheel running under hypobaric hypoxia.

resultsChronic hypobaric hypoxia induced pronounced skeletal muscle dysfunction and mitochondrial structural disorganization. However, exercise preconditioning combined with hypoxic training attenuated these hypoxia-induced impairments. Both hypoxic skeletal muscles in vivo and C2C12 cells in vitro exhibited significant Sirt1 downregulation. Notably, overexpression of Sirt1 or treatment with exercise mimetics partially reversed hypoxia-induced myotube atrophy and mitochondrial dysfunction through the PGC-1α/FoxO3a signaling pathway-a mechanism shared with exercise interventions.

conclusionThis study uncovers exercise as a potent inducer of hypoxia resilience through Sirt1-dependent mitochondrial repair and multicellular crosstalk (vascular-endothelial-satellite cell axis). Our "train-before-you-climb" approach could transform how we prepare for high-altitude living, offering a drug-free way to keep muscles strong where the air is thin.

Indexed as

Altitude SicknessHypoxiaMitochondriaMuscle Fibers, SkeletalMuscle, SkeletalPhysical Conditioning, AnimalSirtuin 1AltitudeAnimalsCell LineDisease Models, AnimalMaleMiceMice, Inbred C57BLMitochondria, MuscleMuscular AtrophySirt1 protein, mouseSirtuin 1ExerciseHypoxiaMitochondriaSirt1Skeletal muscle dysfunction

Identifiers

PMID40835003
PMCPMC13131521

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.