Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation

Most drugs used to treat sarcopenia are ineffective. Herein, the long‐acting anti‐sarcopenic properties of cerium oxide nanoparticles (CeNPs) and their underlying mechanisms of action are investigated in aging mice (treated with 4‐hydroperoxy cyclophosphamide (4‐HC)). CeNPs (size, 27.5 nm) with a fl...

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Main Authors: Wei‐Chih Lien, Yu‐Ling Yu, Ya‐Jyun Liang, Chia‐Yih Wang, Yang‐Chen Lin, Huei‐Cih Chang, Feng‐Huei Lin, Hui‐Min David Wang
Format: Article
Language:English
Published: Wiley-VCH 2025-08-01
Series:Small Science
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Online Access:https://doi.org/10.1002/smsc.202500208
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author Wei‐Chih Lien
Yu‐Ling Yu
Ya‐Jyun Liang
Chia‐Yih Wang
Yang‐Chen Lin
Huei‐Cih Chang
Feng‐Huei Lin
Hui‐Min David Wang
author_facet Wei‐Chih Lien
Yu‐Ling Yu
Ya‐Jyun Liang
Chia‐Yih Wang
Yang‐Chen Lin
Huei‐Cih Chang
Feng‐Huei Lin
Hui‐Min David Wang
author_sort Wei‐Chih Lien
collection DOAJ
description Most drugs used to treat sarcopenia are ineffective. Herein, the long‐acting anti‐sarcopenic properties of cerium oxide nanoparticles (CeNPs) and their underlying mechanisms of action are investigated in aging mice (treated with 4‐hydroperoxy cyclophosphamide (4‐HC)). CeNPs (size, 27.5 nm) with a fluorite crystallization structure are synthesized and subjected to X‐ray diffraction and gas adsorption analyzes. Synthesized CeNPs exhibit Ce3+ and Ce4+ on their surfaces, a specific surface area within the standard range, and self‐regenerative antioxidative functions. Synthesized CeNPs reduce reactive oxygen species (ROS) levels and exhibit good biocompatibility in muscle satellite (C2C12) cells. According to Rotarod, tensile, and histological analyzes, CeNP treatment once per week in 4‐HC‐treated mice markedly increases muscle strength and the cross‐sectional muscle tissue area relative to that in control mice. Next‐generation sequencing identifies CILP2 as a key differentially upregulated gene common to aging muscle tissues and satellite cells in the presence of ROS. Quantitative polymerase chain reaction and western blotting confirm CILP2, Serpine1, phospho‐p21, Atrogin‐1, and Cxcl10 downregulation in CeNP‐treated mice (compared with 4‐HC‐treated mice); in vitro CILP2 knockdown results in Serpine1 and phospho‐p21 downregulation. These findings confirm the long‐acting effects of CeNPs against sarcopenia in older individuals.
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spelling doaj-art-657d3160f6bf4ca2bf3b1d68493801ee2025-08-20T03:41:21ZengWiley-VCHSmall Science2688-40462025-08-0158n/an/a10.1002/smsc.202500208Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 DownregulationWei‐Chih Lien0Yu‐Ling Yu1Ya‐Jyun Liang2Chia‐Yih Wang3Yang‐Chen Lin4Huei‐Cih Chang5Feng‐Huei Lin6Hui‐Min David Wang7Department of Physical Medicine and Rehabilitation National Cheng Kung University Hospital College of Medicine National Cheng Kung University No. 138, Sheng Li Road Tainan 704 Taiwan (R.O.C.)Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University No. 1, Sec. 4, Roosevelt Rd Taipei 106 Taiwan (R.O.C.)Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University No. 1, Sec. 4, Roosevelt Rd Taipei 106 Taiwan (R.O.C.)Department of Cell Biology and Anatomy College of Medicine National Cheng Kung University No. 1, University Road Tainan 701 Taiwan (R.O.C.)Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University No. 1, Sec. 4, Roosevelt Rd Taipei 106 Taiwan (R.O.C.)Department of Physical Medicine and Rehabilitation College of Medicine No. 1, University Road Tainan 701 Taiwan (R.O.C.)Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University No. 1, Sec. 4, Roosevelt Rd Taipei 106 Taiwan (R.O.C.)Graduate Institute of Biomedical Engineering National Chung Hsing University No. 145, Xingda Rd., South Dist. Taichung City 402 Taiwan (R.O.C.)Most drugs used to treat sarcopenia are ineffective. Herein, the long‐acting anti‐sarcopenic properties of cerium oxide nanoparticles (CeNPs) and their underlying mechanisms of action are investigated in aging mice (treated with 4‐hydroperoxy cyclophosphamide (4‐HC)). CeNPs (size, 27.5 nm) with a fluorite crystallization structure are synthesized and subjected to X‐ray diffraction and gas adsorption analyzes. Synthesized CeNPs exhibit Ce3+ and Ce4+ on their surfaces, a specific surface area within the standard range, and self‐regenerative antioxidative functions. Synthesized CeNPs reduce reactive oxygen species (ROS) levels and exhibit good biocompatibility in muscle satellite (C2C12) cells. According to Rotarod, tensile, and histological analyzes, CeNP treatment once per week in 4‐HC‐treated mice markedly increases muscle strength and the cross‐sectional muscle tissue area relative to that in control mice. Next‐generation sequencing identifies CILP2 as a key differentially upregulated gene common to aging muscle tissues and satellite cells in the presence of ROS. Quantitative polymerase chain reaction and western blotting confirm CILP2, Serpine1, phospho‐p21, Atrogin‐1, and Cxcl10 downregulation in CeNP‐treated mice (compared with 4‐HC‐treated mice); in vitro CILP2 knockdown results in Serpine1 and phospho‐p21 downregulation. These findings confirm the long‐acting effects of CeNPs against sarcopenia in older individuals.https://doi.org/10.1002/smsc.202500208agingcartilage intermediate layer protein 2cellular senescencecerium oxide nanoparticlesreactive oxygen speciessarcopenia
spellingShingle Wei‐Chih Lien
Yu‐Ling Yu
Ya‐Jyun Liang
Chia‐Yih Wang
Yang‐Chen Lin
Huei‐Cih Chang
Feng‐Huei Lin
Hui‐Min David Wang
Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
Small Science
aging
cartilage intermediate layer protein 2
cellular senescence
cerium oxide nanoparticles
reactive oxygen species
sarcopenia
title Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
title_full Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
title_fullStr Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
title_full_unstemmed Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
title_short Cerium Oxide Nanoparticles Achieve Long‐Lasting Senescence Inhibition in an Aging Mouse Model of Sarcopenia via Reactive Oxygen Species Scavenging and CILP2 Downregulation
title_sort cerium oxide nanoparticles achieve long lasting senescence inhibition in an aging mouse model of sarcopenia via reactive oxygen species scavenging and cilp2 downregulation
topic aging
cartilage intermediate layer protein 2
cellular senescence
cerium oxide nanoparticles
reactive oxygen species
sarcopenia
url https://doi.org/10.1002/smsc.202500208
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