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间充质干细胞分泌的外泌体通过上调 SIRT1 表达延缓大脑衰老。

Exosomes secreted by mesenchymal stem cells delay brain aging by upregulating SIRT1 expression.

机构信息

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, 130000, Jilin, China.

Yibin Jilin University Research Institute, Jilin University, Yibin, 644000, Sichuan, China.

出版信息

Sci Rep. 2023 Aug 14;13(1):13213. doi: 10.1038/s41598-023-40543-5.

Abstract

The increase in the aging population has seriously affected our society. Neurodegenerative diseases caused by aging of the brain significantly impact the normal life of the elderly, and delaying brain aging is currently the focus of research. SIRT1 is a viable therapeutic target, and there is mounting evidence that it plays a significant role in the aging process. Mesenchymal stem cell-derived exosomes (MSC-Exos) have gained widespread interest as nanotherapeutic agents because of their ability to be injected at high doses to reduce the immune response. The present study focused on the ameliorative effect of MSC-Exos on aging mice and the potential mechanisms of this effect on cognitive impairment and brain aging. In this study, we first tested the neuroprotective effects of MSC-Exos in vitro on HO-induced oxidative damage in BV2 cells. An in vivo SAMP8 rapid senescence mouse model showed that MSC-Exos significantly increased SIRT1 gene expression in senescent mice. In addition, MSC-Exos also had an anti-apoptotic effect and reduced oxidative stress in the brains of SAMP8 senescent mice. In conclusion, MSC-Exos may exert neuroprotective effects and help prevent brain senescence in SAMP8 mice by activating the SIRT1 signaling pathway.

摘要

人口老龄化的增加严重影响了我们的社会。大脑衰老引起的神经退行性疾病显著影响老年人的正常生活,延缓大脑衰老目前是研究的重点。SIRT1 是一个可行的治疗靶点,越来越多的证据表明它在衰老过程中发挥着重要作用。间充质干细胞衍生的外泌体(MSC-Exos)作为纳米治疗剂引起了广泛的关注,因为它们能够以高剂量注射以减少免疫反应。本研究专注于 MSC-Exos 对衰老小鼠的改善作用及其对认知障碍和大脑衰老的潜在作用机制。在这项研究中,我们首先在体外测试了 MSC-Exos 对 HO 诱导的 BV2 细胞氧化损伤的神经保护作用。体内 SAMP8 快速衰老小鼠模型表明,MSC-Exos 显著增加了衰老小鼠中的 SIRT1 基因表达。此外,MSC-Exos 还对 SAMP8 衰老小鼠的大脑具有抗凋亡作用,并降低了氧化应激。总之,MSC-Exos 可能通过激活 SIRT1 信号通路对 SAMP8 小鼠发挥神经保护作用并有助于预防大脑衰老。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e9/10425430/1b3d3c7a3eb4/41598_2023_40543_Fig1_HTML.jpg

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