金丝桃素能促进小鼠的长寿和胰岛素敏感性。

IF 5.1 2区 生物学 Q2 CELL BIOLOGY
Cells Pub Date : 2024-10-18 DOI:10.3390/cells13201727
Nadine Nagy, Kathryn S Czepiel, Gernot Kaber, Darko Stefanovski, Aviv Hargil, Nina Pennetzdorfer, Robert Targ, Saranya C Reghupaty, Thomas N Wight, Robert B Vernon, Rebecca L Hull-Meichle, Payton Marshall, Carlos O Medina, Hunter Martinez, Anissa Kalinowski, Rudolph D Paladini, Stavros Garantziotis, Joshua W Knowles, Paul L Bollyky
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引用次数: 0

摘要

鉴于细胞外基质聚合物透明质酸(HA)与长寿有关,我们询问 4-甲基伞形酮(4-MU)这种 HA 合成抑制剂是否会影响小鼠的寿命。我们设计了一项对常规 C57BL/6J 小鼠长期服用 4-MU 的前瞻性研究。我们发现,4-MU 可使小鼠的中位生存期从 122 周(对照组)延长至 154 周(4-MU),延长了 32 周(经 Log-rank Mantel Cox 检验,p < 0.0001)。4-MU治疗小鼠的最长寿命从159周延长到194周。通过胰岛素耐量试验(ITT)和频繁静脉内葡萄糖耐量试验(FSIVGTTs)测量,4-MU 可提高胰岛素敏感性,而胰岛素敏感性是一种已知可调节寿命的代谢参数。我们进一步观察到,4-MU 处理的小鼠在摄入相同数量食物的情况下体重减轻,这表明 4-MU 处理改变了能量消耗。然而,在该模型中,我们没有观察到组织中 HA 含量的变化。我们的结论是,4-MU 可促进胰岛素敏感性和长寿,但其潜在机制和 HA 的贡献尚不清楚。4-MU已被多个国家批准用于治疗肝胆疾病,目前正在进行调查和临床开发,以治疗多种慢性炎症。这些数据表明,4-MU 对组织代谢的有益影响可能包括对长寿的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice.

Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.

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来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
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