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The results from a human pilot study that focused on treating idiopathic pulmonary fibrosis with senescent cell-clearing drugs has been published.The drugs target aged and damaged cells,which are thought to be a reason we age and get sick,把它们从尸体上取下来。

衰老细胞与衰老

随着我们年龄的增长,increasing numbers of our cells become dysfunctional,进入一种叫做衰老的状态。衰老细胞不再分裂或支持其所属的组织和器官;相反,they secrete a range of harmful inflammatory chemical signals,统称为衰老相关分泌表型(sasp)。

Dr.来自巴克老化研究所的朱迪丝·坎皮西,along with her research team,identified that senescent cells secreted the various harmful chemicals that characterize the SASP in 2008,当人们真正开始对衰老细胞感兴趣时[1]。2010,在这项初步研究的基础上,Dr.Campisi went on to show the link between the SASP and cancer [2].

The SASP increases inflammation,损害组织修复和功能,导致免疫系统失灵,并增加患癌症等与年龄相关疾病的风险。它还可以通过所谓的旁观者效应,鼓励附近的其他健康细胞衰老。Therefore,这些细胞中的一小部分会造成很大的伤害。

通常情况下,衰老的细胞在被免疫系统清除之前会通过一个称为凋亡的自我毁灭过程来自我毁灭。Unfortunately,随着我们年龄的增长,免疫系统变弱,衰老的细胞开始在体内积聚。The accumulation of senescent cells is considered to be one of the reasons why we age and develop age-related diseases.

It has been suggested that the clearance of senescent cells might help address a number of age-related diseases at once,由于衰老细胞被认为是我们衰老的根本原因之一。可以去除这些有害物质的药物,受损细胞被称为消毒剂.

老年医学人体试验结果

这个新的publicationby researchers at the Mayo Clinic,包括詹姆斯·柯克兰,one of the pioneers of senolytic drugs,shows the results of a pilot study that uses dasatinib and quercetin to treat idiopathic pulmonary fibrosis [3].

Pulmonary fibrosis causes scarring of the lung tissue,随着时间的推移,肺功能逐渐丧失。当疾病的起源不明时,it is called idiopathic pulmonary fibrosis,或IPF。这种疾病的治疗方案非常有限,目前尚无已知的治疗方法。

The researchers in this new study tested a combination of dasatinib and quercetin,在小鼠身上测试的最早的抗衰老药物组合之一,显示出有益的结果,particularly for the cardiovascular system [4-5].It was also shown in a previous study that clearing senescent cells using dasatinib plus quercetin was able to alleviate idiopathic pulmonary fibrosis (IPF)-related dysfunction in a mouse model of the disease.

14名IPF患者被招募参与这项初步研究,最初的结果,while leaving room for improvement,are promising.

物理功能评估为6分钟步行距离,4-m gait speed,and chair-stands time was significantly and clinically-meaningfully improved (p < .05).肺功能,clinical chemistries,frailty index (FI-LAB),报告的健康状况没有变化。DQ对循环SASP因子的影响尚不明确。but correlations were observed between change in function and change in SASP-related matrix-remodeling proteins,microRNAs,and pro-inflammatory cytokines (23/48 markers r ≥ 0.50).

值得注意的是,这只是一个小规模的试点研究,尚未确定最佳的人体剂量和频率。Typically,下一步是开展更大规模的研究,以确定这种剂量。

研究人员还注意到,这些结果有助于对达沙替尼加槲皮素在更大范围内的评价。randomized,以及老年相关疾病的对照试验。换言之,they would like to test senolytics in larger studies for various age-related diseases,and the results certainly support doing exactly that.

Conclusion

These initial results are positive,尽管还有很大的改进空间。这两种药物的结合似乎也比其他药物更倾向于特定的细胞和组织类型,就像其他的抗衰老药物一样,which were discovered after dasatinib and quercetin were originally shown to clear senescent cells.可能需要将不同的生理学结合起来鸡尾酒会of sorts to fully clear out all the unwanted senescent cells,由于不同的衰老细胞似乎使用不同的生存途径来逃避凋亡,而且没有一种药物可以针对所有人。

我们积极欢迎这些早期结果,并期待着对多种年龄相关疾病的大规模研究的开始。考虑到衰老细胞似乎与大多数甚至不是所有的年龄相关疾病有关,前面还有一些令人兴奋的可能性。

文学类

〔1〕科普,J.P.PatilC.K.,Rodier,F.,太阳Y.,穆尼奥兹,D.P.Goldstein,J.,… & Campisi,J.(2008)。Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.PLoS biology,6(12),e301.

[2] Coppé,J.P.DesprezP.Y.,Krtolica,A.,和坎皮西,J.(2010)。衰老相关的分泌表型:肿瘤抑制的阴暗面。病理性机械疾病年度回顾,5,99-118.

[3] Nambiar,A.,Justice,J.,PascualR.,Tchkonia,T.,LebrasseurN.KirklandJ.,…克里切夫斯基,S.(2018)。Targeting pro-inflammatory cells in idiopathic pulmonary fibrosis: an open-label pilot study of dasatinib and quercitin.胸部,154(4),395A-396A.

〔4〕朱,Y.,Tchkonia,T.,皮尔茨卡拉瓦T.,Gower,A.C.,丁H。Giorgadze,N.…&奥哈拉,S.P.(2015)。The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.Aging cell,14(4),644-658.

[5] Roos,C.M.,Zhang,B.,Palmer,A.K.,OgrodnikMB.,皮尔茨卡拉瓦T.,塔尔吉n.名词M.,……朱Y.(2016).Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice.老化细胞。

关于作者

Steve Hill

作为科学作家和健康长寿的忠实倡导者,以及促进长寿的技术,Steve为社区提供了数百篇教育文章,interviews,播客,helping the general public to better understand aging and the means to modify its dynamics.他的资料可以在H+杂志上找到,长寿记者,Psychology Today and Singularity Weblog.他是这本书的合著者。预防所有人老化”—大众探索循证方法延长健康生活的指南(出版)。
  1. 1月10日,2019

    I hope the FDA (Fostering Agony and Death) does not dilly dally and hold up this potentially huge breakthroug for years.我是一名ALCO成员,认识Greg Fehey Bill Faloon和Aubrey Degrey。who are also involved in anti-aging research.You might be interested in RAADfest

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