抗衰老药物:达沙替尼和槲皮素又一个被神话的例子?

2022-08-08 MedSci原创 MedSci原创

2015年,美国梅奥医学中心的 James Kirkland 博士等在 Aging Cell 杂志发表论文,报道了一类选择性杀伤衰老细胞的药物组合——Senolytics。达沙

2015年,美国梅奥医学中心的 James Kirkland 博士等在 Aging Cell 杂志发表论文,报道了一类选择性杀伤衰老细胞的药物组合——Senolytics。达沙替尼和槲皮素组成(D+Q)的Senolytics疗法可以选择性地诱导衰老细胞死亡。其中,达沙替尼可清除衰老的人脂肪细胞祖细胞,而槲皮素可以杀伤衰老的人内皮细胞和小鼠骨髓干细胞,两者联合使用效果更强。

当然,在抗衰老的保健品中还看到槲皮素Quercetin 和 非瑟酮Fisetin的组合

Senolytic Activator®  36 vegetarian capsules - Life Extension

随后Senolytics很快被开发成为商业化产品!

Senolytics 是一类选择性清除衰老细胞 (SC) 的药物。第一种抗衰老药物达沙替尼、槲皮素、非瑟酮和 Navitoclax 是使用假设驱动的方法发现的。 SC随着年龄的增长和多种慢性疾病的发病部位积累,包括占发病率、死亡率和健康支出大部分的疾病。最有害的 SC 对细胞凋亡具有抗性,并且具有上调的抗凋亡途径,这些途径可以保护 SC 免受自身炎症性衰老相关分泌表型 (SASP) 的影响,使它们能够存活,尽管会杀死邻近的细胞。 Senolytics 会暂时抑制这些 SCAP,导致那些具有组织破坏性 SASP 的 SC 细胞凋亡。因为 SC 需要数周时间才能重新积累,所以可以间歇性地使用抗衰老药物——一种“打了就跑”的方法。在临床前模型中,senolytics 可延迟、预防或减轻虚弱、癌症和心血管、神经精神、肝脏、肾脏、肌肉骨骼、肺、眼、血液、代谢和皮肤疾病以及器官移植、放射和癌症治疗的并发症。正如预期的那样,针对作为多种疾病“根本原因”贡献者的基本衰老机制的药物,senolytics 的潜在用途是千变万化的,在临床前研究中可能缓解 40 多种疾病,为治疗与年龄相关的功能障碍和疾病开辟了一条新途径。 senolytics 的早期试验表明,它们可以减少衰老细胞,减少炎症并缓解人类的虚弱。针对糖尿病、特发性肺纤维化、阿尔茨海默病、COVID-19、骨关节炎、骨质疏松症、眼病和骨髓移植以及儿童癌症幸存者的临床试验正在进行或开始。在完成此类研究之前,将 senolytics 用于临床试验之外还为时过早。

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D+Q组合确实在开展相关临床试验,见:https://clinicaltrials.gov/ct2/show/NCT04946383 但是达沙替尼,毕竟是一款抗癌药物,很多专家并不建议这一组合作为抗衰老药物使用。

梅斯小编发现,目前针对D+Q的相关基础研究,也相当多,似乎发现它在清除多个器官的衰老细胞中起到作用,包括眼部,神经等。但是D+Q能否真正走上临床,仍然任重而道远。

参考资料:

https://longevity.technology/avoid-the-use-of-dq-as-a-senolytic-therapy/

https://clinicaltrials.gov/ct2/show/NCT04946383

Baboota RK, Spinelli R, Erlandsson MC, Brandao BB, Lino M, Yang H, Mardinoglu A, Bokarewa MI, Boucher J, Kahn CR, Smith U.Chronic hyperinsulinemia promotes human hepatocyte senescence.Mol Metab (IF: 7.42; Q1). 2022 Jul 21:101558

Thadathil N, Selvarani R, Mohammed S, Nicklas EH, Tran AL, Kamal M, Luo W, Brown JL, Lawrence MM, Borowik AK, Miller BF, Van Remmen H, Richardson A, Deepa SS.Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma.Aging Cell . 2022 Jul 23. doi: 10.1111/acel.13676

Gao F, Wang L, Wu B, Ou Q, Tian H, Xu J, Jin C, Zhang J, Wang J, Lu L, Xu GT.Elimination of senescent cells inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells.Exp Eye Res . 2022 Aug 1:109207. doi: 10.1016/j.exer.2022.109207

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    2023-05-11 侠胆医心 来自上海

    #达沙替尼##槲皮素#组成(D+Q)的#Senolytics疗法#可以选择性地诱导#衰老#细胞死亡。其中,达沙替尼可清除衰老的人脂肪细胞祖细胞,而槲皮素可以杀伤衰老的人内皮细胞和小鼠骨髓干细胞,两者联合使用效果更强。 还是#保健品#公司速度快,很快就做成保健品了。

    0

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