国际抗衰服务管理中心旗舰店

新冠是一种老年疾病？抗衰药步入新冠临床，看疫情下衰老领域如何发展

2022年12月29日

导读

距新冠疫情全球范围内爆发已过三年，疫情大环境下，从人们寻常的衣食起居（如再难摘下的口罩），到各行业运转，都不可避免受到影响。

以衰老研究领域为例，很多环节都意外成了“限速步骤”：要做实验了，发现样品送不到、试剂买不到，还可能因为隔离，连人都没法到……

图注：早前上海疫情管控时，派派身边研究人员的“艰难科研路”

可以说，这场疫情是全人类面临的重大挑战之一，但疫情下，负面、消极的问题易被看见和放大，很容易让人忽略了正向上生长的力量，而衰老科学发展便是其中之一。

疫情当前，人们对于健康、长寿的追求，上升至前所未有的高度，衰老学科也硬是于狂风暴雨中裹挟前行，杀出了一条光明路。

在日复一日与病毒的斡旋中，研究人员们发现，无论是临床一线的观察报告，还是实验室内严谨的数据分析，新冠患者中老年人群的重症率、死亡率都居高不下，而同样免疫力可能没那么好的孩童，重症或死亡情况却是少之又少[1-3]。

图注：各年龄段新冠患者重症收治率（蓝色条带）、死亡率（白色条带）

在这一“非偶然事件”的推动下，2020年10月，知名学府哈佛大学的研究人员发现，老年人群感染新冠绝非偶然，病毒受体ACE2基因就是更喜欢在老化的肺部表达，“COVID-19（新冠）是一种新兴的衰老疾病”[4]！

此后不久，另一顶级高校耶鲁大学也发声，通过对重症新冠患者的研究，从细胞层面证实了年龄因素在病毒感染中的决定性作用[5]。

而有着近百年悠久历史的美国老年医学会对新冠更是“穷追不舍”，以“New Research on COVID-19 and Aging”（关于新冠与衰老的新研究）为主题的系列新闻资讯，直接从年头更新到了年尾[6]。

图注：2020年美国老年医学会关于“新冠与衰老”的部分科研报道

随后，一众高质量研究又陆续指出，新冠与人类端粒长度、损伤程度[7, 8]，以及细胞、免疫系统衰老[9, 10]，都存在密不可分的关联。且学者们也发现，简单从流行病学角度出发，根本无法解答许多研究矛盾或冲突点（就好比为何老人更易感或易致死）[11]。

至此，“新冠老年病”的地位算是被坐实了。

可以说，全球疫情背景下，新冠凭借一己之力，将衰老研究拉至聚光灯下，让这一本来或被认为“是天命”、“没什么好研究”的科学领域得到空前关注。

衰老研究幸得新冠“一手提携”，也深知饮水思源之真谛，于是，在治愈新冠上，数位声名远播的抗衰干将被派出，步步为营，走上了治疗新冠的临床探究。

二甲双胍

有着“神药”美称的二甲双胍，堪称是“老药新用”的典范，在本职“降糖”之外，被发现具有消炎[12]、抑制癌细胞干性[13]、调节肠道菌群[14]、抗衰[15]等多重功效。

在2020年全球多项临床观察中，二甲双胍被发现能显著提升新冠病患的存活率[16-19]，如疫情早期我国学者便发现，服用二甲双胍能让患有糖尿病的新冠病人死亡率降低约3倍[20]。

“二甲双胍辅助新冠治疗”的理论研究仍在进行中，当下多认为，二甲双胍能通过激活AMPK通路促使病毒刺突蛋白构象变化[21, 22]、调节机体炎症因子（如IL-6、趋化因子配体）[23, 24]、减少嗜中性粒细胞-细胞外陷阱（NET）而降低细胞因子风暴等[25, 26]，从病毒侵入过程到机体免疫系统调节，多方位狙击新冠病毒。

Senolytics

直译为“摧毁衰老”的Senolytics，能通过选择性清除衰老细胞、改善机体慢性炎症，从而延长生物体寿命[27]，是近年来抗衰领域的热门干预措施。

如此瞩目的Senolytics，其“抗病毒”功效也渐被发掘。借助Senolytics疗法，本已存在的老化细胞，或是因病毒感染而加速衰老、僵化的细胞，都能被打扫的干干净净，病毒再难诱发可怖的炎症风暴，无论是研究中最常用的模式生物小鼠[28]，还是取自人体的细胞[9]，存活率都得到极大提升。

这一突破性发现也同时将Science、Nature两大顶刊收入囊中，如此光辉之下，“抗衰药治新冠”、“消除衰老治愈新冠”，两件曾以为毫无关联的事，终是殊途同归，走到了一起。

图注：草莓中富含Senolytics明星物质漆黄素

NMN和NR

作为生物体重要辅酶NAD+的两大明星前体，NMN与NR虽说一直来相争不断，但新冠面前，却似乎达成一致，靠着“有效提升机体NAD+水平，改善NAD+代谢”，在多项临床研究中收获了加速新冠患者康复的好结果[29, 30]。

今年2月和4月，两项分别来自抗衰领域著名学者哈佛教授大卫．辛克莱和我国中科院学者的高质量报道，均再度证实了NMN可通过调控机体免疫过程（NF-κB通路与NLRP3炎症小体）[31]、肺部炎症环境与血液流通[32]，对抵抗新冠肺炎起到积极作用。

病毒变异、疫情往复，NAD+前体若真能于其中献力一二，对人类战胜疫情，倒也是幸事一桩。

雷帕霉素

5月，曾获“最佳科学技术报道奖”的《麻省理工科技评论》，专文讨论了抗衰老药物在治疗新冠上的潜在应用价值[33]，雷帕霉素，这一由美国官方老龄化机构NIA筛选而来的“续命明星”，自然也被提及。

作为可有效调控mTOR信号通路、逆转免疫衰老的物质，学术界一直存在“雷帕霉素及其类似物可能有助于预防或改善新冠肺炎”的猜想[34, 35]。为了证实该设想可行性，目前有三项人体临床正在活跃进行中。

表：正在开展的以新冠肺炎为适应症的雷帕霉素人体临床试验。来源ClinicialTrials. gov

他汀类

此外，在MIT 5月的报道中，一类经典的降脂药他汀类药物，也被提及。这位同样是“老药新用”的“多面手”，被证实可通过调节细胞周期[36]、诱导细胞自噬[37]、延缓血管老化[38]等途径，达到延年抗衰的妙用。

而在与新冠病毒短兵相见的战场上，一查方见其不凡功勋。

早在2020年8月，我国科研团队就利用万余名临床确诊新冠患者的大样本数据，发现使用他汀类药物的人群死亡风险更低（为5.2%，对照组为9.4%）[39]。之后，陆续有报道指出，他汀类药物可能借助免疫调节而非降低血脂，达到对抗新冠的目的[40]。

目前，英国政府机构NIHR（国家卫生与保健研究所）正资助一项名为“HEAL-COVID”（治愈新冠）的人体临床[41]，以探究每日服用他汀类药物能否帮助人类从新冠病毒感染中恢复，并预防“长新冠”症状（注：Long COVID，指感染新冠康复后，出现长期困倦、头疼、呼吸困难等症状[42]）。

图注：“HEAL-COVID”人体临床官网

“新冠是一种老年病”、“年龄成为新冠最大的诱发因素”……愈来愈多新冠联系衰老的证据，让衰老领域成功“等到东风来”。

3月15日，美国总统拜登签署《综合拨款法案》，宣布NIA（美国国家老龄化研究所）本年度预算将超过42亿美元，相比2021财年的金额总体增加8.2%[43]。同时，NIH（美国国立卫生研究院）在人类健康方面的研究经费也将从1000万陡增至1.1亿美元[44]。

除了衰老领域的官方机构不差钱，全球多国顶级富豪们也毫不吝啬、狂掷亿金，纷纷下海衰老研究，其中，动静最大的必是被誉为“最强抗衰老公司”Altos Labs，以及近来沙特王室怒投10亿美元成立的抗衰老基金会。而这些海量资金，无疑将极大推动衰老研究进展与后续转化。

钱已火速到位，人才紧跟其后，在NIA不久前刚公布的资助项目中，宣布鼓励优秀科研人员进行衰老相关的高级培训或工作[45]。

一拍即合，有钱有人，还有国家官方机构当后台，抗衰领域的未来不可谓不光芒万丈。

时光派点评

如同“抗衰圣地”巴克研究所所长、衰老领域顶级学者Eric Verdin所言：

“COVID-19让我们注意到很多曾经被忽略的事情，就比如我们对老年人免疫缺陷、免疫衰老的忽视，这不仅针对新冠疫情，也对其他病毒感染，甚至癌症，都有重大意义。”

面对抗衰，这一看似逆天改命的事情，我们尚且能找到光明的方向，那么，面对当下反复的疫情，我们也定能保护好自我，最终控制并战胜病毒。

国际抗衰服务管理中心

原文阅读

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[41] https://heal-covid.net/

[42] https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html

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