Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna.
Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna.
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DOI：
10.1126/sciadv.abo5482
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发表时间：
2022-09-16
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
发育与衰老密切相关，但以发育为目标的基因是否能延长寿命仍是未知数。在这里，我们让遗传多样性的UMHET3小鼠在生命的前45天接受雷帕霉素治疗。这些小鼠生长缓慢，一生都比对照组小。他们的生育年龄被推迟，而不影响后代的数量。治疗足以延长中位寿命10%，对男性的影响最大，并有助于保持健康，如虚弱指数评分，步态速度，葡萄糖和胰岛素耐量测试。从机制上讲，治疗小鼠的肝脏转录组和表观基因组在治疗完成时更年轻。与小鼠类似，雷帕霉素在发育过程中的暴露显著延长了大型蚤的寿命，并缩小了其体型。总的来说，研究结果表明，在发育期间进行短期雷帕霉素治疗是一种新的长寿干预措施，通过减缓发育和衰老来发挥作用，这表明衰老可能在生命早期就已经成为目标。仅在生命早期给予雷帕霉素可延长雄性小鼠的寿命和健康寿命，并延长大型蚤的寿命。
Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life. Rapamycin given only during early life extends life span and health span of male mice and extends life span of Daphnia magna.
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影响因子：
29
作者：
Martinez-Miguel VE;Lujan C;Espie-Caullet T;Martinez-Martinez D;Moore S;Backes C;Gonzalez S;Galimov ER;Brown AEX;Halic M;Tomita K;Rallis C;von der Haar T;Cabreiro F;Bjedov I
通讯作者：
Bjedov I
影响因子：
7.3
作者：
Ma S;Gladyshev VN
通讯作者：
Gladyshev VN
影响因子：
7.7
作者：
Houde VP;Brûlé S;Festuccia WT;Blanchard PG;Bellmann K;Deshaies Y;Marette A
通讯作者：
Marette A
影响因子：
7.7
作者：
Lu YX;Regan JC;Eßer J;Drews LF;Weinseis T;Stinn J;Hahn O;Miller RA;Grönke S;Partridge L
通讯作者：
Partridge L
影响因子：
4.8
作者：
Coschigano, KT;Holland, AN;Kopchick, JJ
通讯作者：
Kopchick, JJ