小柯机器人

近日，美国罗彻斯特大学Vera Gorbunova等研究人员合作发现，通过裸鼹鼠Has2增加透明质酸可改善小鼠的健康寿命。相关论文于2023年8月23日在线发表在《自然》杂志上。

为了研究高分子量透明质酸（HMM-HA）的益处是否可以转移到其他动物物种，研究人员产生了过表达裸鼹鼠透明质酸合成酶2基因（nmrHas2）的转基因小鼠。nmrHas2小鼠在多个组织中显示出透明质酸水平的增加、自发癌症和诱发癌症发病率的降低、寿命的延长和健康状况的改善。nmrHas2小鼠的转录组特征向长寿物种转变。在nmrHas2小鼠身上观察到的最显著变化是多个组织的炎症减轻。

HMM-HA通过多种途径减轻炎症，包括对免疫细胞的直接免疫调节作用、氧化应激保护以及在衰老过程中改善肠道屏障功能。这些益处是由HMM-HA带来的，并非nmrHas2基因所特有。这些发现表明，裸鼹鼠演化出的长寿机制可以输出到其他物种，并为利用HMM-HA改善寿命和健康寿命开辟了新的道路。

据悉，丰富的HMM-HA有助于抗癌，也可能有助于最长寿的啮齿类动物（裸鼹鼠）的长寿。

附：英文原文

Title: Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice

Author: Zhang, Zhihui, Tian, Xiao, Lu, J. Yuyang, Boit, Kathryn, Ablaeva, Julia, Zakusilo, Frances Tolibzoda, Emmrich, Stephan, Firsanov, Denis, Rydkina, Elena, Biashad, Seyed Ali, Lu, Quan, Tyshkovskiy, Alexander, Gladyshev, Vadim N., Horvath, Steve, Seluanov, Andrei, Gorbunova, Vera

Issue&Volume: 2023-08-23

Abstract: Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent—the naked mole-rat1,2. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2). nmrHas2 mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHas2 mice shifted towards that of longer-lived species. The most notable change observed in nmrHas2 mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmrHas2 gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.

DOI: 10.1038/s41586-023-06463-0

Source: https://www.nature.com/articles/s41586-023-06463-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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