Aging:人“生理年龄”第一次被成功逆转!

2019-09-09 佚名 中国生物技术网

表观遗传学时钟可以用来测量个体的生理年龄,并且一些研究表明在校正了年龄、性别、吸烟情况、身体质量指数(BMI)、疾病史以及血细胞计数等传统风险因素后仍然准确。

表观遗传学时钟可以用来测量个体的生理年龄,并且一些研究表明在校正了年龄、性别、吸烟情况、身体质量指数(BMI)、疾病史以及血细胞计数等传统风险因素后仍然准确。

9月8日发表在《Aging》上的一项在美国加州进行的小型临床试验研究,首次将逆转人体表观遗传时钟变为可能。在为期一年的试验里,9名健康志愿者服用了包括生长激素和两种糖尿病药物在内的药物“鸡尾酒”。研究人员通过分析个体基因组上的标记,发现参与者们平均减少了2.5岁的生物学年龄,并且他们的免疫系统也显示出恢复活力的迹象。

即使对试验组织者来说,这一结果也是令人惊讶的,但是该研究团队警告说,这项研究还只是初步的,因为试验规模很小,并且没有包括对照组。

在试验中进行表观遗传学分析的加州大学洛杉矶分校的遗传学家Steve Horvath说:“我本以为表观遗传时钟只是放慢脚步,但没想到还能逆转。这真是有点儿未来感!”

德国亚琛大学的细胞生物学家Wolfgang Wagner说:“这是有可能的,但结果并不是绝对可靠,因为这项研究规模很小,也没有得到很好的控制。”

生命的标志

表观遗传时钟依赖于人体的表观基因组,包括标记DNA的甲基化。这些标签的模式会跟踪个体的生理年龄在一生中发生变化,它或迟于实际年龄,或超过实际年龄。

科学家通过选择基因组中的DNA甲基化位点来构建表观遗传时钟。在过去的几年里,Horvath作为表观遗传学时钟研究的先驱,开发了一些精确的时钟。

这项最新试验主要是为了测试生长激素是否可以安全地用于人类以恢复胸腺组织。胸腺位于肺和胸骨之间,对于有效的免疫功能至关重要。白细胞在骨髓中产生,成熟于胸腺,并在那里成为T细胞,帮助身体对抗感染和癌症。但在青春期后,腺体开始萎缩,并逐渐被脂肪堵塞。

来自动物和一些人体研究的证据表明,生长激素可以刺激胸腺再生。但这种激素也会促进糖尿病,因此该试验包括两种广泛使用的抗糖尿病药物——脱氢表雄酮(DHEA)和二甲双胍,用于药物鸡尾酒疗法。

胸腺再生、免疫恢复和胰岛素缓解(TRIIM)试验测试了年龄在51岁至65岁之间的9名白人男性。该项目由免疫学家Gregory Fahy领导,他是洛杉矶Intervene Immune公司的首席科学官和联合创始人。该试验于2015年5月获得美国食品和药物管理局的批准。几个月后,在加州斯坦福医学中心开始进行。

Fahy对胸腺的痴迷可以追溯到1986年,当时他读到一篇研究:科学家为了恢复大鼠的免疫系统,将生长激素分泌细胞移植到其体内。但令他惊讶的是,竟然没有人对这个结果进行临床试验。10年后,46岁的他给自己服用生长激素和脱氢表雄酮一个月,并发现自己胸腺有了一些再生。

在TRIIM试验中,科学家们在治疗期间从参与者那里采集了血液样本。测试表明,每个参与者的血细胞计数都恢复了活力。研究人员还使用磁共振成像(MRI)确定研究开始和结束时胸腺的组成。他们发现,在7名参与者中,积累的脂肪已经被再生的胸腺组织所取代。



图片来源:《Aging》



胸腺MRI外观的变化。图片来源:《Aging》

时光“倒转”

检查药物对参与者表观遗传时钟的影响是事后的想法。当Fahy找到Horvath进行分析时,临床研究已经完成。

Horvath使用了四种不同的表观遗传时钟来评估每个参与者的生物学年龄,他发现在所有测试中每个参与者的情况都有显著的逆转。他说:“这告诉我,这种疗法的生物学效应是强大的,更重要的是,在停止试验6个月后提供最终血样的6名参与者中,这种影响依然存在。因为我们可以跟踪每个人体内的变化,而且每个人的效果都非常强烈,所以我非常乐观!”

现在,研究人员已经在测试二甲双胍预防年龄相关常见疾病的潜力,如癌症和心脏病。Fahy说:“鸡尾酒中的三种药物可能通过独特的机制分别对生物衰老产生影响。”

Intervene Immune正计划开展更大规模的研究,其中包括不同年龄组和不同种族的人以及女性。

Fahy说:“胸腺再生可能对免疫系统低下的人有用,包括老年人。肺炎和其他传染病是70岁以上人群死亡的主要原因。”

爱丁堡Herriot-Watt大学的癌症免疫学家Sam Palmer说:“看到血液中免疫细胞的扩增是令人兴奋的。这不仅对传染病,而且对癌症和整体老龄化都有着巨大的影响。”

原始出处:
Gregory M. Fahy, Robert T. Brooke, James P. Watson, et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging. 08 September 2019.

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    2019-09-17 14607dd8m74暂无昵称

    学习了

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    2019-09-15 14607dd8m74暂无昵称

    学习了

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    2019-09-10 jiazhoudexue

    学习了,谢谢分享!

    0

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    2019-09-10 深海的鱼

    学习学习学习

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    2019-09-10 184****9840

    学习了,谢谢分享

    0

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