ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Protective effect of exercise on animals with sepsis: a systematic review of the existing literature.BMC infectious diseases · 2025Pooled it
- Association of PPARGC1A Gly428Ser (rs8192678) polymorphism with potential for athletic ability and sports performance: A meta-analysis.PloS one · 2019Pooled it
- Inotodiol prevents age-related muscle wasting by restoring mitochondrial function through liver X receptor beta signaling.Signal transduction and targeted therapy · 2026Article
- Inhibition of TWEAK/Fn14 Ameliorates Sarcopenic Obesity by Restoring Mitochondrial Biogenesis via the AMPK/SIRT1/PGC-1α Axis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Mitochondrial sirtuins, key regulators of aging.Life medicine · 2025Review
- Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus.BMC genomics · 2025Article
- Aging: A struggle for beneficial to overcome negative factors made by muscle and bone.Mechanisms of ageing and development · 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
- Formoterol promotes mitochondrial biogenesis, improves liver regeneration, and suppresses liver injury and inflammation after liver resection in mice with endotoxemia.International journal of physiology, pathophysiology and pharmacology · 2025Article
- Amelioration of aging-induced muscular decline by black soybean (Frontiers in immunology · 2025Article
- Circulating PGC-1α and MOTS-c Peptide as Potential Mitochondrial Biomarkers in Patients Undergoing Aortic Valve Replacement.Biologics : targets & therapy · 2025Article
- Review
- Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.Pflugers Archiv : European journal of physiology · 2024Review
- PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response.Antioxidants (Basel, Switzerland) · 2023Review
- PGC-1s shape epidermal physiology by modulating keratinocyte proliferation and terminal differentiation.iScience · 2023Article
- Targeting Mitochondria to Control Ageing and Senescence.Pharmaceutics · 2023Review
- Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link.Annals of medicine · 2023Review
- Metabolomic profiling reveals muscle metabolic changes following iliac arteriovenous fistula creation in mice.American journal of physiology. Renal physiology · 2022Article
- Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Diabetes risk increases significantly with age and correlates with lower oxidative capacity in muscle. Decreased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and target gene pathways involved in mitochondrial oxidative phosphorylation are associated with muscle insulin resistance, but a causative role has not been established. We sought to determine whether a decline in Pgc-1α and oxidative gene expression occurs during aging and potentiates the development of age-associated insulin resistance. Muscle-specific Pgc-1α knockout (MKO) mice and wild-type littermate controls were aged for 2 yr. Genetic signatures of skeletal muscle (microarray and mRNA expression) and metabolic profiles (glucose homeostasis, mitochondrial metabolism, body composition, lipids, and indirect calorimetry) of mice were compared at 3, 12, and 24 mo of age. Microarray and gene set enrichment analysis highlighted decreased function of the electron transport chain as characteristic of both aging muscle and loss of Pgc-1α expression. Despite significant reductions in oxidative gene expression and succinate dehydrogenase activity, young mice lacking Pgc-1α in muscle had lower fasting glucose and insulin. Consistent with loss of oxidative capacity during aging, Pgc-1α and Pgc-1β expression were reduced in aged wild-type mouse muscle. Interestingly, the combination of age and loss of muscle Pgc-1α expression impaired glucose tolerance and led to increased fat mass, insulin resistance, and inflammatory markers in white adipose and liver tissues. Therefore, loss of Pgc-1α expression and decreased mitochondrial oxidative capacity contribute to worsening glucose tolerance and chronic systemic inflammation associated with aging.
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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.