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S-Adenosyl-l-Methionine Alleviates the Senescence of MSCs Through the PI3K/AKT/FOXO3a Signaling Pathway.
Shang, Lipeng; Li, Xiaoxia; Ding, Xiaoyan; Liu, Guoxiang; Pan, Zhen; Chen, Xiangyan; Wang, Yuelei; Li, Bing; Wang, Ting; Zhao, Robert Chunhua.
Afiliación
  • Shang L; School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Li X; Institute of Stem Cell and Regenerative Medicine, School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Ding X; School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Liu G; Institute of Stem Cell and Regenerative Medicine, School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Pan Z; School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Chen X; Institute of Stem Cell and Regenerative Medicine, School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Wang Y; Weifang People's Hospital, Kuiwen district, Weifang 261041, People's Republic of China.
  • Li B; School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Wang T; School of Basic Medicine, Qingdao University, Qingdao 266071, People's Republic of China.
  • Zhao RC; Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People's Republic of China.
Stem Cells ; 42(5): 475-490, 2024 May 15.
Article en En | MEDLINE | ID: mdl-38427800
ABSTRACT
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 (100 µM for 2 hours), SAM (50 and 100 µM) was revealed to alleviate the senescence of MSCs, and also attenuated the level of reactive oxygen species and enhanced the adipogenic and osteogenic differentiation in senescent MSCs. In a premature aging mouse model (subcutaneously injected with 150 mg/kg/day d-galactose in the neck and back for 7 weeks), SAM (30 mg/kg/day 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 forkhead box O3 (FOXO3a) was proved to be associated with the antisenescence 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Transducción de Señal / Senescencia Celular / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Células Madre Mesenquimatosas / Proteína Forkhead Box O3 Límite: Animals / Humans / Male Idioma: En Revista: Stem Cells Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: S-Adenosilmetionina / Transducción de Señal / Senescencia Celular / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Células Madre Mesenquimatosas / Proteína Forkhead Box O3 Límite: Animals / Humans / Male Idioma: En Revista: Stem Cells Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido