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MyMD-1 improves health span and prolongs lifespan in old mice: A non-inferiority study to rapamycin
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 4.3 ) Pub Date : 2022-08-02 , DOI: 10.1093/gerona/glac142
Elena Sabini 1 , Alison O'Mahony 2 , Patrizio Caturegli 1
Affiliation  

Aging and age-related diseases represent a compelling therapeutic goal for senolytics and drugs targeting inflammatory or metabolic pathways. We compared MyMD-1, a synthetic derivative of the alkaloid myosmine capable of suppressing TNF-α production, to rapamycin, the best characterized drug endowed with anti-aging properties. In vivo, a longitudinal cohort of 54 C57BL/6 mice, 19-month-old at the start, was randomized to receive MyMD-1, high-dose (126 ppm) rapamycin, or low-dose (14 ppm) rapamycin plus metformin. Each treatment arm included 18 mice (10 females and 8 males) and was followed for 16 months or until death. Lifespan was significantly longer in MyMD-1 than rapamycin (P= 0.019 versus high-dose and 0.01 versus low-dose) in a Cox survival model that accounted for sex and serum levels of IL-6, TNF-α, and IL-17A. MyMD-1 also improved several health span characteristics, resulting in milder body weight loss, greater muscle strength, and slower progression to frailty. In vitro, MyMD-1 and rapamycin were compared using a panel of 12 human primary cell systems (BioMAP Diversity PLUS™) where a total of 148 biomarkers are measured. MyMD-1 possessed anti-proliferative, anti-inflammatory, and anti-fibrotic properties. Many were shared with rapamycin, but MyMD-1 was more active in the inhibition of pro-inflammatory and pro-fibrotic biomarkers. Overall, MyMD-1 emerges as a new compound that, even when begun at an advanced age, induces beneficial effects on health and lifespan by modulating inflammation and tissue remodeling.

中文翻译:

MyMD-1 改善老年小鼠的健康寿命并延长寿命:一项对雷帕霉素的非劣效性研究

衰老和与年龄相关的疾病是针对炎症或代谢途径的抗衰老药物和药物的一个引人注目的治疗目标。我们将 MyMD-1(一种能够抑制 TNF-α 生成的生物碱肌苷的合成衍生物)与雷帕霉素(最具抗衰老特性的药物)进行了比较。在体内,54 只 19 个月大的 C57BL/6 小鼠的纵向队列被随机分配接受 MyMD-1、高剂量 (126 ppm) 雷帕霉素或低剂量 (14 ppm) 雷帕霉素加二甲双胍. 每个治疗组包括 18 只小鼠(10 只雌性和 8 只雄性),并被随访 16 个月或直至死亡。在考虑了 IL-6、TNF-α 和 IL-17A 的性别和血清水平的 Cox 生存模型中,MyMD-1 的寿命明显长于雷帕霉素(P = 0.019 与高剂量和 0.01 与低剂量) . MyMD-1 还改善了几个健康跨度特征,导致更温和的体重减轻、更强的肌肉力量和更慢的衰弱进展。在体外,使用一组 12 种人类原代细胞系统 (BioMAP Diversity PLUS™) 对 MyMD-1 和雷帕霉素进行了比较,其中测量了总共 148 种生物标志物。MyMD-1 具有抗增殖、抗炎和抗纤维化特性。许多与雷帕霉素共享,但 MyMD-1 在抑制促炎和促纤维化生物标志物方面更为活跃。总的来说,MyMD-1 作为一种新化合物出现,即使是在高龄开始,也可以通过调节炎症和组织重塑对健康和寿命产生有益影响。使用一组 12 个人类原代细胞系统 (BioMAP Diversity PLUS™) 对 MyMD-1 和雷帕霉素进行了比较,其中测量了总共 148 个生物标志物。MyMD-1 具有抗增殖、抗炎和抗纤维化特性。许多与雷帕霉素共享,但 MyMD-1 在抑制促炎和促纤维化生物标志物方面更为活跃。总的来说,MyMD-1 作为一种新化合物出现,即使是在高龄开始,也可以通过调节炎症和组织重塑对健康和寿命产生有益影响。使用一组 12 个人类原代细胞系统 (BioMAP Diversity PLUS™) 对 MyMD-1 和雷帕霉素进行了比较,其中测量了总共 148 个生物标志物。MyMD-1 具有抗增殖、抗炎和抗纤维化特性。许多与雷帕霉素共享,但 MyMD-1 在抑制促炎和促纤维化生物标志物方面更为活跃。总的来说,MyMD-1 作为一种新化合物出现,即使是在高龄开始,也可以通过调节炎症和组织重塑对健康和寿命产生有益影响。但 MyMD-1 在抑制促炎和促纤维化生物标志物方面更为活跃。总的来说,MyMD-1 作为一种新化合物出现,即使是在高龄开始,也可以通过调节炎症和组织重塑对健康和寿命产生有益影响。但 MyMD-1 在抑制促炎和促纤维化生物标志物方面更为活跃。总的来说,MyMD-1 作为一种新化合物出现,即使是在高龄开始,也可以通过调节炎症和组织重塑对健康和寿命产生有益影响。
更新日期:2022-08-02
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