S-adenosyl-L-methionine alleviates the senescence of MSCs through the PI3K/AKT/FOXO3a signaling pathway
© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com..
Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-L-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100μM for 2h), SAM (50μM and 100μM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of ROS and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/d D-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/d by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of FOXO3a was proved to be associated with the anti-senescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Stem cells (Dayton, Ohio) - (2024) vom: 01. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shang, Lipeng [VerfasserIn] |
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| Links: |
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| Themen: |
Differentiation |
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| Anmerkungen: |
Date Revised 01.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/stmcls/sxae010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369176790 |
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| 520 | |a © The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a Cellular senescence significantly affects the proliferative and differentiation capacities of mesenchymal stem cells (MSCs). Identifying key regulators of senescence and exploring potential intervention strategies, including drug-based approaches, are active areas of research. In this context, S-adenosyl-L-methionine (SAM), a critical intermediate in sulfur amino acid metabolism, emerges as a promising candidate for mitigating MSC senescence. In a hydrogen peroxide-induced MSC aging model (100μM for 2h), SAM (50μM and 100μM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of ROS and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/d D-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/d by gavage for 5 weeks) was shown to delay the overall aging process while increasing the number and thickness of bone trabeculae in the distal femur. Mechanistically, activation of PI3K/AKT signaling and increased phosphorylation of FOXO3a was proved to be associated with the anti-senescence role of SAM. These findings highlight that the PI3K/AKT/FOXO3a axis in MSCs could play a crucial role in MSCs senescence and suggest that SAM may be a potential therapeutic drug for MSCs senescence and related diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PI3K/AKT/FOXO3a | |
| 650 | 4 | |a S-adenosyl-L-methionine | |
| 650 | 4 | |a differentiation | |
| 650 | 4 | |a mesenchymal stem cells | |
| 650 | 4 | |a senescence | |
| 700 | 1 | |a Li, Xiaoxia |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Guoxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiangyan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuelei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Robert Chunhua |e verfasserin |4 aut | |
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