重新使用已在诊所批准的药物,以在标签外用作老年保护剂,对抗衰老机制的化合物,是快速降低社会年龄相关疾病发病率的有希望的方法。最近的几项研究发现,一类药物-核苷逆转录酶抑制剂(NRTIs)-最初开发用于治疗癌症和人类免疫缺陷病毒(HIV)感染,可以被重新利用来减缓衰老过程。有趣的是,这些研究提出了针对衰老的多种标志的补充机制。在分子水平上,NRTIs抑制LINE-1元素,减少DNA损伤,受益于“基因组不稳定”的衰老标志。在细胞器层面,NRTIs抑制线粒体翻译,激活ATF-4,抑制胞质翻译,并以与“蛋白质停滞丧失”衰老标志相关的方式延长蠕虫的寿命。同时,在细胞水平上,NRTIs抑制P2X7介导的炎症小体激活,减少炎症并改善“细胞间通讯改变”的衰老标志。NRTIs对人类衰老健康的未来发展将需要平衡毒副作用与有益效果,这可能部分是通过刺耳语发生的。
Repurposing drugs already approved in the clinic to be used off-label as geroprotectors, compounds that combat mechanisms of aging, are a promising way to rapidly reduce age-related disease incidence in society. Several recent studies have found that a class of drugs-nucleoside reverse transcriptase inhibitors (
NRTIs)-originally developed as treatments for cancers and human immunodeficiency virus (HIV) infection, could be repurposed to slow the aging process. Interestingly, these studies propose complementary mechanisms that target multiple hallmarks of aging. At the molecular level,
NRTIs repress LINE-1 elements, reducing DNA damage, benefiting the hallmark of aging of \'Genomic Instability\'. At the organellar level,
NRTIs inhibit mitochondrial translation, activate ATF-4, suppress cytosolic translation, and extend lifespan in worms in a manner related to the \'Loss of Proteostasis\' hallmark of aging. Meanwhile, at the cellular level,
NRTIs inhibit the P2X7-mediated activation of the inflammasome, reducing inflammation and improving the hallmark of aging of \'Altered Intercellular Communication\'. Future development of
NRTIs for human aging health will need to balance out toxic side effects with the beneficial effects, which may occur in part through hormesis.