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抗衰老生物材料鲟鱼硫酸软骨素上调抗氧化和 SIRT-1/c-fos 基因表达,重编程干细胞衰老并延长寿命。

Anti-aging biomaterial sturgeon chondroitin sulfate upregulating anti-oxidant and SIRT-1/c-fos gene expression to reprogram stem cell senescence and prolong longevity.

机构信息

School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110301, Taiwan.

Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 110301, Taiwan.

出版信息

Biomater Sci. 2023 Jun 27;11(13):4522-4536. doi: 10.1039/d2bm01997c.

Abstract

Aging involves tissue and cell potential dysfunction characterized by stem cell senescence and extracellular matrix microenvironment (ECM) alteration. Chondroitin sulfate (CS), found in the ECM of normal cells and tissues, aids in maintaining tissue homeostasis. Here, CS-derived biomaterial (CSDB) from sturgeon is extracted to investigate its antiaging effect in senescence-accelerated mouse prone-8 (SAMP8) mice and elucidate the underlying mechanism of its action. Although CSDB has been widely extracted from different sources and used as a scaffold, hydrogel, or drug carrier for the treatment of various pathological diseases, CSDB has not yet been used as a biomaterial for the amelioration of senescence and aging features. In this study, the extracted sturgeon CSDB showed a low molecular weight and comprised 59% 4-sulfated CS and 23% 6-sulfated CS. In an study, sturgeon CSDB promoted cell proliferation and reduced oxidative stress to inhibit stem cell senescence. In an study, after oral CSDB treatment of SAMP8 mice, the stem cells were extracted to analyze the p16Ink4a and p19Arf gene-related pathways, which were inhibited and then SIRT-1 gene expression was upregulated to reprogram stem cells from a senescence state for retarding aging. In an study, CSDB also restored the aging-phenotype-related bone mineral density and skin morphology to prolong longevity. Thus, sturgeon CSDB may be useful for prolonging healthy longevity as an anti-aging drug.

摘要

衰老是指组织和细胞功能潜在障碍的一种现象,其特征是干细胞衰老和细胞外基质微环境(ECM)改变。硫酸软骨素(CS)存在于正常细胞和组织的 ECM 中,有助于维持组织的内稳态。本研究从鲟鱼中提取 CS 衍生的生物材料(CSDB),以研究其在衰老加速模型小鼠(SAMP8)中的抗衰老作用,并阐明其作用机制。虽然 CSDB 已广泛从不同来源提取,并被用作支架、水凝胶或药物载体,用于治疗各种病理疾病,但 CSDB 尚未被用作改善衰老和老化特征的生物材料。在本研究中,提取的鲟鱼 CSDB 具有低分子量,其中 4-硫酸化 CS 占 59%,6-硫酸化 CS 占 23%。在一项研究中,鲟鱼 CSDB 促进细胞增殖,减少氧化应激,抑制干细胞衰老。在另一项研究中,用 CSDB 对 SAMP8 小鼠进行口服治疗后,提取干细胞,分析 p16Ink4a 和 p19Arf 基因相关通路,这些通路被抑制,然后 SIRT-1 基因表达上调,使干细胞从衰老状态重编程,从而延缓衰老。在另一项研究中,CSDB 还恢复了与衰老表型相关的骨密度和皮肤形态,以延长寿命。因此,鲟鱼 CSDB 可能作为一种抗衰老药物,有助于延长健康长寿。

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