Evidence map›Paper›PMID 39887939›Full record

ArticleJournal of cachexia, sarcopenia and muscle2025

Defective Cystic Fibrosis Transmembrane Conductance Regulator Accelerates Skeletal Muscle Aging by Impairing Autophagy/Myogenesis.

Ziyi Chen, Jiankun Xu, Peijie Hu, Wanting Du, Junjiang Chen, Xiaotian Zhang, Wei Zhou, Jiayang Gao, Yuantao Zhang, Bingyang Dai and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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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

18 authors.

Ziyi ChenMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Jiankun XuMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Peijie HuDepartment of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Wanting DuDepartment of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Junjiang ChenDepartment of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Xiaotian ZhangDepartment of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Wei ZhouState Key Laboratory of Respiratory Disease for Allergy Shenzhen Key Laboratory of Allergy & Immunology School of Medicine, Shenzhen University, Shenzhen, China.
Jiayang GaoSchool of Life Sciences, Centre for Cell & Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.
Yuantao ZhangMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Bingyang DaiMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Guangshuai NieOrthopaedic Research Centre, Department of Orthopaedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Jun HuOrthopaedic Research Centre, Department of Orthopaedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Liangbin ZhouMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Shunxiang XuMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Hisao Chang ChanEpithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Wing-Hoi CheungMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Ye Chun RuanDepartment of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Ling QinMusculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.ORCID https://orcid.org/0000-0001-6173-6167

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRegenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.

methodsVastus lateralis biopsy samples from male and female human subjects (n = 23) of 7- to 86-year-old and gastrocnemii tissues from mice of 4- to 29-month-old were examined for CFTR expression. Skeletal muscle tissues or cultured myoblasts from mice carrying CFTR mutation (DF508) at 4- to 18-month-old were used for assessment of muscle mass, contractile force and regenerative capacity as well as myogenic and autophagy signalling. Overexpression of LC3-β, an autophagy mediator, was conducted to reverse myogenic defects in DF508 myoblasts. Adenoviruses containing CFTR gene or pharmaceuticals that enhance CFTR (VX809) were locally injected into the gastrocnemius or femoris quadricep to rescue age-related skeletal muscle defects in mice.

resultsmRNA levels of CFTR in human vastus lateralis exhibited significantly negative correlations with age (r = -0.87 in males and -0.62 in females, p < 0.05). Gastrocnemius mRNA level of CFTR decreased by 77.7 ± 4.6% in 29-month-old wild-type mice compared to the 4-month-old. At 18-month-old, DF508 mice showed significantly reduced lean mass (by 35.6%), lower specific twitch force of the gastrocnemius (by 46.2%), decrease in fast/slow-twitch muscle isoform ratio as well as downregulation of myogenic (e.g., MYOD and MYOG) or autophagy/mitophagy (e.g., LC3-β) genes, compared to age-matched wild-types. Post-injury gastrocnemius regeneration was found impaired in DF508 mice. Myoblast cultures from DF508 mice showed defective myogenic differentiation, which was reversed by overexpressing LC3-β. In aged (> 15-month-old) mice, overexpressing CFTR or VX809 restored the expression of autophagy or myogenic genes, increased mitochondrial LC3-β level and improved skeletal muscle mass and function.

conclusionAge-related reduction in skeletal muscle expression of CFTR impairs autophagy and myogenesis, exacerbating skeletal muscle aging. Enhancing CFTR might be a potential treatment strategy for age-related skeletal muscle disorders.

Indexed as

AgingAutophagyCystic Fibrosis Transmembrane Conductance RegulatorMuscle DevelopmentMuscle, SkeletalAdolescentAdultAgedAged, 80 and overAnimalsChildFemaleHumansMaleMiceMiddle AgedCystic Fibrosis Transmembrane Conductance RegulatorautophagyCFTRCFTR‐modulatormitochondriamyogenesisskeletal muscle

Identifiers

PMID39887939
PMCPMC11780116

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.