ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Muscle Organoids Reveal Exercise-Like Contractions Rapidly Promote Muscle Health Via Lamtor1's Signaling to Both AMPK and mTOR.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Acid-sensing ion channel 1a contributes to the calcium/calmodulin-dependent ferroptosis and aggravates intervertebral disc degeneration.Redox report : communications in free radical research · 2026Article
- Exercise Regulates Mitochondrial Quality Control: Maintenance and Remodeling of Skeletal Muscle Homeostasis.Biology · 2026Review
- Special Issue "Alcohol and Inflammation".International journal of molecular sciences · 2026Article
- Type 2 Diabetes Mellitus as a Multisystem Disease: From Insulin Resistance to Organ Crosstalk-A Narrative Review.Biomedicines · 2026Review
- Muscle Organoids Reveal Exercise-Like Contractions Rapidly Promote Muscle Health Via Lamtor1's Signaling to Both AMPK and mTOR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
10 authors.
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Abstract
Exercise triggers molecular changes in skeletal muscles, but distinguishing immediate responses from secondary inter-organ interactions in muscle biopsies remains challenging. Here, this study differentiates human embryonic stem cells (hESCs) into induced skeletal muscle (iMusc) cells to identify hypertrophic factors and generates a novel 3D human iMusc organoid model for studying the direct effects of exercise-like contractions. Transcriptomics profiling reveals iMusc organoids rapidly induced genes associated with calcium signaling, p38/MAPK, EGF/ErbB, and NGF pathways within 1 h, mimicking exercise responses in vivo. Proteomics profiling and in vivo validation reveal rapid activation of both AMPK and mTORC1 signaling, partly through increased Lamtor1 levels, resolving a paradox in exercise biology. Human muscle biopsy analyses reveal Lamtor1 decreases with aging, and increases with exercise. In vivo and organoid experiments both confirm Lamtor1's role in mTORC1-induced strength and AMPK-induced lipid metabolism. Overall, this 3D iMusc organoid model provides insights into primary contraction-induced changes and identifies Lamtor1 as a novel therapeutic target for exercise mimicry.
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