ArticleAging cell2022
Growth differentiation factor 11 accelerates liver senescence through the inhibition of autophagy.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.Aging cell · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- METTL14 mitigates osteoporosis progression by promoting osteogenic differentiation of BMMSCs through improving mitochondrial dysfunction.Journal of molecular histology · 2026Article
- Acyl-CoA-binding protein as a driver of pathological aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cellular senescence in adult pulmonary hypertension: current state and future challenges.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- A novel exploration ofJournal of pharmaceutical analysis · 2025Article
- Esketamine reduces postoperative depression in breast cancer through TREK-1 channel inhibition and neurotransmitter modulation.Cancer cell international · 2025Article
- Dexmedetomidine alleviates intestinal ischemia/reperfusion injury by modulating intestinal neuron autophagy and mitochondrial homeostasis via Nupr1 regulation.Molecular medicine (Cambridge, Mass.) · 2024Article
- Rejuvenation of young blood on aging organs: Effects, circulating factors, and mechanisms.Heliyon · 2024Review
- GDF11: An emerging therapeutic target for liver diseases and fibrosis.Journal of cellular and molecular medicine · 2024Review
- A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes.Protein & cell · 2024Article
- Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver.International journal of molecular sciences · 2024Article
- Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases.International journal of molecular sciences · 2023Review
- All-fiber SPR microfluidic chip for GDF11 detection.Biomedical optics express · 2022Article
- GDF11 Regulates PC12 Neural Stem Cells via ALK5-Dependent PI3K-Akt Signaling Pathway.International journal of molecular sciences · 2022Article
- COX-2/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1/PI3K/AKT/mTOR.International journal of molecular sciences · 2022Article
- Growth differentiation factor 11 accelerates liver senescence through the inhibition of autophagy.Aging cell · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The "rejuvenating" effect of growth differentiation factor 11 (GDF11) is called into question recently, and its role, as well as plausible signaling mechanisms in liver senescence, is unclear. To overexpress or knockdown GDF11, aged male mice are injected with a single dose of adeno-associated viruses-GDF11 or adenovirus-small hairpin RNA-GDF11, respectively. GDF11 overexpression significantly accelerates liver senescence in aged mice, whereas GDF11 knockdown has opposite effects. Concomitantly, autophagic flux is impaired in livers from GDF11 overexpression mice. Conversely, GDF11 knockdown increases autophagic flux. Moreover, rapamycin successfully restores the impaired autophagic flux and alleviates liver senescence in GDF11 overexpression mice, while the GDF11 knockdown-mediated benefits are abolished by the autophagy inhibitor bafilomycin A1. GDF11 leads to a drop in lysosomal biogenesis resulting in defective autophagic flux at autophagosome clearance step. Mechanistically, GDF11 significantly activates mammalian target of rapamycin complex 1 (mTORC1) and subsequently represses transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Inhibition of mTORC1 or TFEB overexpression rescues the GDF11-impaired autophagic flux and cellular senescence. Hepatocyte-specific deletion of GDF11 does not alter serum GDF11 levels and liver senescence. Collectively, suppression of autophagic activity via mTORC1/TFEB signaling may be a critical molecular mechanism by which GDF11 exacerbates liver senescence. Rather than a "rejuvenating" agent, GDF11 may have a detrimental effect on liver senescence.
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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.