ArticleAmerican journal of physiology. Lung cellular and molecular physiology2019
Activation of the mTORC1/PGC-1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium.
Article in American journal of physiology. Lung cellular and molecular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Beyond Membrane Remodeling: Organelle Crosstalk and Convergent Pathology in Centronuclear Myopathy.Muscles (Basel, Switzerland) · 2026Review
- Early mitophagy defects and impaired mitochondrial energy metabolism drive target organ damage progression: lessons from the Fabry heart.bioRxiv : the preprint server for biology · 2026Article
- L-Carnosine Enhances the Proliferation and Myogenic Differentiation of Yanbian Cattle Skeletal Muscle Satellite Cells for Cultured Meat Production via Activating the Akt/mTOR/P70S6K Signaling Pathway.Food science & nutrition · 2026Article
- Mitochondrial quantity-quality imbalance in cellular senescence: practical readouts and minimal assay bundles.BMB reports · 2026Review
- AClinical, cosmetic and investigational dermatology · 2026Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- Oxidative Stress, Inflammation, and Cellular Senescence in Neuropathic Pain: Mechanistic Crosstalk.Antioxidants (Basel, Switzerland) · 2025Review
- Exploring the uncharted role of cell senescence in rare diseases.Orphanet journal of rare diseases · 2025Review
- Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons.Antioxidants (Basel, Switzerland) · 2025Review
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
- Mechanisms of endothelial senescence and vascular aging.Biogerontology · 2025Review
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- rhCC16 Suppresses Cellular Senescence and Ameliorates COPD-Like Symptoms by Activating the AMPK/Sirt1-PGC-1-α-TFAM Pathway to Promote Mitochondrial Function.Journal of cellular and molecular medicine · 2025Article
- Role of Mitochondrial Dynamics in Skin Homeostasis: An Update.International journal of molecular sciences · 2025Review
- The link between Mitochondria and Sarcopenia.Journal of physiology and biochemistry · 2025Review
- Unraveling the ROS-Inflammation-Immune Balance: A New Perspective on Aging and Disease.Aging and disease · 2025Review
- Article
- Modulating mitochondria with natural extract compounds: from bench to clinical therapeutic opportunities for COPD.Frontiers in pharmacology · 2025Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular senescence is a biological process by which cells lose their capacity to proliferate yet remain metabolically active. Although originally considered a protective mechanism to limit the formation of cancer, it is now appreciated that cellular senescence also contributes to the development of disease, including common respiratory ailments such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. While many factors have been linked to the development of cellular senescence, mitochondrial dysfunction has emerged as an important causative factor. In this study, we uncovered that the mitochondrial biogenesis pathway driven by the mammalian target of rapamycin/peroxisome proliferator-activated receptor-γ complex 1α/β (mTOR/PGC-1α/β) axis is markedly upregulated in senescent lung epithelial cells. Using two different models, we show that activation of this pathway is associated with other features characteristic of enhanced mitochondrial biogenesis, including elevated number of mitochondrion per cell, increased oxidative phosphorylation, and augmented mitochondrial reactive oxygen species (ROS) production. Furthermore, we found that pharmacological inhibition of the mTORC1 complex with rapamycin not only restored mitochondrial homeostasis but also reduced cellular senescence to bleomycin in lung epithelial cells. Likewise, mitochondrial-specific antioxidant therapy also effectively inhibited mTORC1 activation in these cells while concomitantly reducing mitochondrial biogenesis and cellular senescence. In summary, this study provides a mechanistic link between mitochondrial biogenesis and cellular senescence in lung epithelium and suggests that strategies aimed at blocking the mTORC1/PGC-1α/β axis or reducing ROS-induced molecular damage could be effective in the treatment of senescence-associated lung 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.