Academic Journal
Manganese overload as a previously underappreciated trigger of cellular senescence: Unraveling mechanisms and therapeutic rescue by the senolytic quercetin.
| Τίτλος: | Manganese overload as a previously underappreciated trigger of cellular senescence: Unraveling mechanisms and therapeutic rescue by the senolytic quercetin. |
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| Συγγραφείς: | Tao Z; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Guo C; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Xu S; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Xiao X; School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Yang B; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Wang S; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Skalny AV; Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Yaroslavl 150000, Russia; Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow 119146, Russia., Tinkov AA; Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Yaroslavl 150000, Russia; Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow 119146, Russia., Aschner M; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Lu R; Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Clinical Experimental Research Center, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Suzhou, Jiangsu 215300, China. Electronic address: lurz@ujs.edu.cn. |
| Πηγή: | Neurotoxicology [Neurotoxicology] 2026 Sep; Vol. 116, pp. 103528. Date of Electronic Publication: 2026 Jul 17. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 7905589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9711 (Electronic) Linking ISSN: 0161813X NLM ISO Abbreviation: Neurotoxicology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2001- : Amsterdam : Elsevier Science Original Publication: Park Forest South, Ill., Pathotox Publishers. |
| Ιατρικοί όροι (MeSH): | Quercetin*/pharmacology , Cellular Senescence*/drug effects , Cellular Senescence*/physiology , Senotherapeutics*/pharmacology , Manganese*/toxicity, Oxidative Stress/drug effects ; Signal Transduction/drug effects ; DNA Damage/drug effects ; beta-Galactosidase/metabolism ; Animals ; Caenorhabditis elegans ; PC12 Cells ; cGAS-STING Signaling Pathway |
| Περίληψη: | Manganese (Mn) is an essential trace element, but excessive Mn exposure is associated with neurotoxicity and aging-related dysfunction. Whether Mn overload promotes cellular senescence and the mechanisms involved remain insufficiently defined. Here, we investigated Mn-induced senescence-associated injury using Caenorhabditis elegans and neuron-like PC12 cells. Mn exposure shortened lifespan, impaired locomotor behavior, altered dopaminergic neuronal signals, and increased senescence-associated β-galactosidase activity in C. elegans. In PC12 cells, Mn induced senescence-associated phenotypes, including reduced viability, enhanced β-galactosidase positivity, telomere attrition, p53/p21 activation, oxidative stress, mitochondrial dysfunction, DNA damage-related alterations, inflammatory responses, and activation of interferon genes (STING)-related signaling. Quercetin, as a senolytic, attenuated Mn-induced oxidative, mitochondrial, inflammatory, and senescence-associated changes, while STING inhibition partially alleviated cell injury and β-galactosidase positivity. These findings suggest the involvement of STING-related signaling in Mn-induced senescence-associated changes and suggest that this process may be pharmacologically attenuated. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cellular senescence; Manganese; Neurotoxicity; Quercetin; STING signaling; Senolytics |
| Substance Nomenclature: | 9IKM0I5T1E (Quercetin) 0 (Senotherapeutics) 42Z2K6ZL8P (Manganese) EC 3.2.1.23 (beta-Galactosidase) |
| Entry Date(s): | Date Created: 20260717 Date Completed: 20260909 Latest Revision: 20260909 |
| Update Code: | 20260910 |
| DOI: | 10.1016/j.neuro.2026.103528 |
| PMID: | 42468696 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-9711 |
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| DOI: | 10.1016/j.neuro.2026.103528 |