ArticleAging cell2023
AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- PEBP4 alleviates muscle wasting in lung cancer cachexia via KEAP1-NRF2-mediated redox homeostasis.Cell death & disease · 2026Article
- Metrnl in health and disease: tissue-specific actions and signaling networks.Apoptosis : an international journal on programmed cell death · 2026Review
- Skeletal Muscle HSF1 Alleviates Age-Associated Sarcopenia and Mitochondrial Function Decline via SIRT3-PGC1α Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metrnl and macrophage polarization: role in skeletal muscle homeostasis and therapeutic potential.Frontiers in immunology · 2026Review
- Targeting Endothelial KDM5A to Attenuate Aging and Ameliorate Age-Associated Metabolic Abnormalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AAV capsids target muscle-resident cells with different efficiencies-A comparative study between AAV8, AAVMYO, and AAVMYO2.Molecular therapy. Methods & clinical development · 2025Article
- Energy Metabolism and Brain Aging: Strategies to Delay Neuronal Degeneration.Cellular and molecular neurobiology · 2025Review
- Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Skeletal muscle growth to combat diabetes and obesity: the potential role of muscle-secreted factors.Obesity (Silver Spring, Md.) · 2025Review
- Review
- Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation.Allergy · 2025Article
- Ucp1 Ablation Improves Skeletal Muscle Glycolytic Function in Aging Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Low serum Metrnl levels are associated with increased risk of sarcopenia in the older adults.European geriatric medicine · 2024Article
- Myospreader improves gene editing in skeletal muscle by myonuclear propagation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Myospreader improves gene editing in skeletal muscle by myonuclear propagation.bioRxiv : the preprint server for biology · 2023Article
- AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions.Aging cell · 2023Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sarcopenia is characterized of muscle mass loss and functional decline in elder individuals which severely affects human physical activity, metabolic homeostasis, and life quality. Physical exercise is considered effective in combating muscle atrophy and sarcopenia, yet it is not feasible to elders with limited mobility. PGC-1α4, a short isoform of PGC-1α, is strongly induced in muscle under resistance training, and promotes muscle hypertrophy. In the present study, we showed that the transcriptional levels and nuclear localization of PGC1α4 was reduced during aging, accompanied with muscle dystrophic morphology, and gene programs. We thus designed NLS-PGC1α4 and ectopically express it in myotubes to enhance PGC1α4 levels and maintain its location in nucleus. Indeed, NLS-PGC1α4 overexpression increased muscle sizes in myotubes. In addition, by utilizing AAV-NLS-PGC1α4 delivery into gastrocnemius muscle, we found that it could improve sarcopenia with grip strength, muscle weights, fiber size and molecular phenotypes, and alleviate age-associated adiposity, insulin resistance and hepatic steatosis, accompanied with altered gene signatures. Mechanistically, we demonstrated that NLS-PGC-1α4 improved insulin signaling and enhanced glucose uptake in skeletal muscle. Besides, via RNA-seq analysis, we identified myokines IGF1 and METRNL as potential targets of NLS-PGC-1α4 that possibly mediate the improvement of muscle and adipose tissue functionality and systemic energy metabolism in aged mice. Moreover, we found a negative correlation between PGC1α4 and age in human skeletal muscle. Together, our results revealed that NLS-PGC1α4 overexpression improves muscle physiology and systematic energy homeostasis during aging and suggested it as a potent therapeutic strategy against sarcopenia and aging-associated metabolic diseases.
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Registered trials
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.