Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor.
Rilmenidine extends lifespan and healthspan in Caenorhabditis elegans via a nischarin I1-imidazoline receptor.
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作者：
能够延长寿命和健康寿命的药物的再利用在翻译老年学方面具有巨大的未开发潜力。在这里，我们搜索了与热量限制具有相似基因表达特征的已知化合物，并确定了利美尼定，一种I1-咪唑啉受体激动剂和治疗高血压的处方药。然后我们展示了在年轻和年长的时候用利美尼定治疗秀丽隐杆线虫可以延长寿命。我们还证明利美尼定治疗线虫的应激恢复能力、健康寿命和寿命益处是由I1-咪唑啉受体NISH-1介导的，这意味着该受体是一个潜在的长寿靶点。与共同的卡路里限制模仿基因特征一致，在卡路里限制的线虫中补充利美尼定、TORC1功能的遗传降低或雷帕霉素治疗不会进一步延长寿命。利美尼定诱导的长寿需要转录因子FOXO/DAF-16和NRF1，2，3/SKN-1。此外，我们还发现，利美尼定诱导的长寿需要自噬，而不是AMPK信号。此外，在服用利美尼定的小鼠的肝脏和肾脏组织中，观察到了类似于热量限制的转录变化。综上所述，这些结果揭示了利美尼定的保护牙齿和潜在的热量限制模拟作用，这需要对这种化合物进行新的研究。利美尼定对线虫具有延长寿命和养生作用，增强抗逆性，增加自噬。利美尼定治疗线虫的应激恢复能力、健康寿命和寿命益处是由I1-咪唑啉受体NISH-1介导的。
Repurposing drugs capable of extending lifespan and health span has a huge untapped potential in translational geroscience. Here, we searched for known compounds that elicit a similar gene expression signature to caloric restriction and identified rilmenidine, an I1‐imidazoline receptor agonist and prescription medication for the treatment of hypertension. We then show that treating Caenorhabditis elegans with rilmenidine at young and older ages increases lifespan. We also demonstrate that the stress‐resilience, health span, and lifespan benefits of rilmenidine treatment in C. elegans are mediated by the I1‐imidazoline receptor nish‐1, implicating this receptor as a potential longevity target. Consistent with the shared caloric‐restriction‐mimicking gene signature, supplementing rilmenidine to calorically restricted C. elegans, genetic reduction of TORC1 function, or rapamycin treatment did not further increase lifespan. The rilmenidine‐induced longevity required the transcription factors FOXO/DAF‐16 and NRF1,2,3/SKN‐1. Furthermore, we find that autophagy, but not AMPK signaling, was needed for rilmenidine‐induced longevity. Moreover, transcriptional changes similar to caloric restriction were observed in liver and kidney tissues in mice treated with rilmenidine. Together, these results reveal a geroprotective and potential caloric restriction mimetic effect by rilmenidine that warrant fresh lines of inquiry into this compound. Rilmenidine has prolongevity and health preserving effects in C. elegans, increased stress resistance and increased autophagy. The stress‐resilience, healthspan, and lifespan benefits of rilmenidine treatment in C. elegans are mediated by the I1‐imidazoline receptor nish‐1.
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Nischarin的突变通过LIMK1和NF-κB途径引起中耳炎。
影响因子：
4.5
作者：
Crompton M;Purnell T;Tyrer HE;Parker A;Ball G;Hardisty-Hughes RE;Gale R;Williams D;Dean CH;Simon MM;Mallon AM;Wells S;Bhutta MF;Burton MJ;Tateossian H;Brown SDM
通讯作者：
Brown SDM
DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Huang, C;Xiong, CJ;Kornfeld, K
通讯作者：
Kornfeld, K
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
64.8
作者：
Herndon, LA;Schmeissner, PJ;Driscoll, M
通讯作者：
Driscoll, M
影响因子：
4.8
作者：
Forster, MJ;Morris, P;Sohal, RS
通讯作者：
Sohal, RS