Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction.
Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction.
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DOI：
10.1111/acel.12194
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发表时间：
2014-06
期刊：
影响因子：
7.8
通讯作者：
Strong R
中科院分区：
文献类型：
--
作者：
Miller RA;Harrison DE;Astle CM;Fernandez E;Flurkey K;Han M;Javors MA;Li X;Nadon NL;Nelson JF;Pletcher S;Salmon AB;Sharp ZD;Van Roekel S;Winkleman L;Strong R
雷帕霉素是一种mTOR激酶抑制剂，当以比我们先前研究中使用的剂量高三倍的剂量进行测试时，遗传异质性小鼠的中位寿命增加了23%（雄性）至26%（雌性）;两性的最大寿命也增加了。在评估的每个剂量下，雷帕霉素对女性寿命的延长幅度大于男性，这可能反映了该药物血液水平的性二态性。在饮食限制的小鼠中观察到的一些内分泌和代谢变化在暴露于雷帕霉素的小鼠中没有观察到，并且在雷帕霉素治疗的小鼠和饮食限制的小鼠中，参与外源性生物质代谢的肝脏基因的表达模式也相当不同，这表明这两种延长小鼠寿命的干预措施在许多方面不同。
Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet-restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects.
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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：
64.5
作者：
Melo JA;Ruvkun G
通讯作者：
Ruvkun G
影响因子：
7.8
作者：
Harrison DE;Strong R;Allison DB;Ames BN;Astle CM;Atamna H;Fernandez E;Flurkey K;Javors MA;Nadon NL;Nelson JF;Pletcher S;Simpkins JW;Smith D;Wilkinson JE;Miller RA
通讯作者：
Miller RA
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S
DOI：
10.1093/gerona/glq155
发表时间：
2010-12-01
影响因子：
5.1
作者：
Flurkey, Kevin;Astle, Clinton M.;Harrison, David E.
通讯作者：
Harrison, David E.