年龄相关性损伤在动物模型中的逆转

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Age-related impairments reversed in animal model

Date: 日期:July 6, 2020 2020年7月6日Source: 来源:University of Bern 伯恩大学Summary: 摘要:Researchers demonstrate in an animal model that age-related frailty and immune decline can be halted and even partially reversed using a novel cell-based therapeutic approach. 研究人员在动物模型中证明,使用一种新的基于细胞的治疗方法,与年龄相关的脆弱和免疫力下降可以停止,甚至部分逆转Share: 分享:    FULL STORY 完整故事


Eosinophils surrounded | Credit: © Kateryna_Kon / stock.adobe.com

Eosinophils surrounded by red blood cells (stock image). 嗜酸性粒细胞周围的红细胞(股票图片)Credit: © Kateryna_Kon / stock.adobe.com

Frailty and immune decline are two main features of old age. Researchers from the University of Bern and the University Hospital Bern now demonstrate in an animal model that these two age-related impairments can be halted and even partially reversed using a novel cell-based therapeutic approach.

体质虚弱和免疫力下降是老年人的两个主要特征。来自伯恩大学和伯尔尼大学医院的研究人员现在在动物模型中证明,这些与年龄相关的损伤可以通过一种新的基于细胞的治疗方法来停止甚至部分逆转。

Elderly people are more prone to infectious diseases as the function of their immune system continuously declines with progression of age. This becomes especially apparent during seasonal influenza outbreaks or the occurrence of other viral diseases such as COVID-19. As the efficacy of vaccination in the elderly is strongly reduced, this age group is particularly vulnerable to such infectious pathogens and often shows the highest mortality rate. In addition to the age-related immune decline aged individuals are commonly affected by frailty that negatively impacts quality-of-life. Even though the average life-expectancy for humans continuous to rise, living longer is often associated with age-related health issues.

随着年龄的增长,老年人的免疫系统功能不断下降,他们更容易患上传染病综合症。这在季节性流感爆发或其他病毒性疾病如新型冠状病毒肺炎中尤为明显。由于老年人接种疫苗的效力大大降低,这一年龄组特别容易受到这种传染病病原体的影响,而且往往表现出最高的死亡率。除了与年龄有关的免疫力下降,老年人通常受到体弱的影响,这对生活质量产生负面影响。尽管人类的平均预期寿命不断上升,但是长寿往往与年龄相关的健康问题有关。

Important role of belly fat in aging processes identified

确认腹部脂肪在衰老过程中的重要作用

Researchers from the Department for BioMedical Reserarch (DBMR) and the Institute of Pathology at the University of Bern as well as the University Hospital Bern (Inselspital) have set out to identify new approaches to improve health-span in a fast-growing aging population. For many years scientists speculated that chronic low-grade inflammation accelerates aging processes and the development of age-related disorders. An international team of researchers under Bernese guidance has now demonstrated that visceral adipose tissue, known as belly fat, crucially contributes to the development of chronic low-grade inflammation. Scientist around Dr. Mario Noti, formerly at the Institute of Pathology of the University of Bern and Dr. Alexander Eggel from the Department for BioMedical Research (DBMR) of the Universität of Bern reported that certain immune cells in the belly fat play and an essential role in regulating chronic low-grade inflammation and downstream aging processes. They could show, that these immune cells may be used to reverse such processes. The findings of this study have been published in the scientific journal Nature Metabolism and were further highlighted by a News and Views editorial article.

来自生物医学研究部、伯恩大学病理学研究所以及伯尔尼大学医院的研究人员已经开始寻找新的方法来改善快速增长的老龄人口的健康。多年以来,科学家们推测慢性轻度炎症会加速衰老进程和老年相关疾病的发展。在伯恩斯的指导下,一个国际研究小组已经证明了内脏脂肪组织,即腹部脂肪,对慢性低度炎症的发展起着至关重要的作用。前伯恩大学病理学研究所的 Mario Noti 博士和伯尔尼大学生物医学研究免疫学系的 Alexander Eggel 博士报告说,腹部脂肪中的某些免疫细胞在调节慢性低度炎症和下游衰老过程中起重要作用。他们可以证明,这些免疫细胞,可以用来逆转这些过程。这项研究的结果已经发表在科学期刊《自然—- 新陈代谢》上,并在新闻和观点杂志的一篇社论文章中得到了进一步的强调。

Belly fat as a source of chronic inflammation

腹部脂肪是慢性炎症的来源

The team around Dr. Noti and Dr. Eggel could demonstrated that a certain kind of immune cells, known as eosinophils, which are predominantly found in the blood circulation, are also present in belly fat of both humans and mice. Although classically known to provide protection from parasite infection and to promote allergic airway disease, eosinophils located in belly fat are responsible to maintain local immune homeostasis. With increasing age the frequency of eosinophils in belly fat declines, while the number of pro-inflammatory macrophages increases. Owing to this immune cell dysbalance, belly fat turns into a source of pro-inflammatory mediators accumulating systemically in old age.

诺蒂博士和艾格尔博士周围的团队可以证明,某种被称为嗜酸性粒细胞的免疫细胞,主要存在于血液循环中,也存在于人类和老鼠的腹部脂肪中。虽然经典的知道提供保护,从寄生虫感染和促进过敏性呼吸道疾病,嗜酸性粒细胞位于腹部脂肪负责维持局部免疫稳态。随着年龄的增长,腹部脂肪中嗜酸性粒细胞的出现频率下降,而促炎巨噬细胞的数量增加。由于这种免疫细胞失衡,腹部脂肪成为促炎症介质的来源,在老年时全身累积。

Eosinophil cell therapy promotes rejuvenation

嗜酸性粒细胞治疗促进恢复活力

In a next step, the researchers investigated the possibility to reverse age-related impairments by restoring the immune cell balance in visceral adipose tissue. “In different experimental approaches, we were able to show that transfers of eosinophils from young mice into aged recipients resolved not only local but also systemic low-grade inflammation,” says Dr. Eggel. “In these experiments, we observed that transferred eosinophils were selectively homing into adipose tissue,” adds Dr. Noti. This approach had a rejuvenating effect on the aged organism. As a consequence, aged animals showed significant improvements in physical fitness as assessed by endurance and grip strength tests. Moreover, the therapy had a rejuvenating effect on the immune system manifesting in improved vaccination responses of aged mice.

在下一步,研究人员研究了通过恢复内脏脂肪组织的免疫细胞平衡来逆转年龄相关损伤的可能性。“在不同的实验方法中,我们能够证明从年轻小鼠转移到老年接受者体内的嗜酸性粒细胞不仅可以解决局部炎症,而且可以解决全身的低度炎症,”埃格尔博士说。“在这些实验中,我们观察到转移的嗜酸性粒细胞选择性地定位到脂肪组织中,” Noti 博士补充说。这种方法对老化的机体有一个返老还童的效果。因此,通过耐力和握力测试,老年动物的身体素质显著提高。此外,该疗法对老龄小鼠的免疫系统具有恢复活力的作用,表现为免疫应答的改善。

Translating findings into clinics

将调查结果转化到诊所

“Our results indicate that the biological processes of aging and the associated functional impairments are more plastic than previously assumed,” states Dr. Noti. Importantly, the observed age-related changes in adipose immune cell distribution in mice were also confirmed in humans. “A future direction of our research will be to now leverage the gained knowledge for the establishment of targeted therapeutic approaches to promote and sustain healthy aging in humans,” says Dr. Eggel.

Noti 博士说: “我们的研究结果表明,衰老的生物学过程和相关的功能损伤比以前假设的更具可塑性。”。重要的是,在小鼠中观察到的与年龄有关的脂肪免疫细胞分布的变化在人类中也得到了证实。“我们未来的研究方向将是现在利用所获得的知识建立有针对性的治疗方法,以促进和维持人类的健康老龄化,”埃格尔博士说。

This study has been supported by the VELUX STIFTUNG, the FONDATION ACTERIA, and funds of the FreeNovation and medical-biological science research programs of Novartis.

这项研究得到了 VELUX STIFTUNG、 ACTERIA 基金会和诺华公司 FreeNovation 和医学生物科学研究项目基金的支持。

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