Sex differences in lifespan extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling.
Sex differences in lifespan extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling.
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DOI：
10.1111/acel.12656
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发表时间：
2017-12
期刊：
影响因子：
7.8
通讯作者：
Miller RA
中科院分区：
文献类型：
--
作者：
Garratt M;Bower B;Garcia GG;Miller RA
延长小鼠寿命的干预措施可以显示出实质性的两性异形。在这里，我们表明，两种药物治疗，阿卡波糖（ACA）和17-α雌二醇（17 aE 2），男性特异性寿命延长，仅在男性中，与胰岛素敏感性增加和葡萄糖耐量改善相关。女性，显示较小（ACA）或没有寿命延长（17 aE 2），不从药物治疗中获得这些代谢益处。我们发现，这些男性特异性代谢改善与肝脏mTORC 2信号传导增强、Akt活性增加和FOXO 1a磷酸化相关，这些变化可能促进男性的代谢健康和生存。通过性腺切除术操纵性激素水平，我们表明，这些代谢途径中的性别特异性变化是由男性和女性性腺激素以相反的方向调节的：去势男性对药物治疗的代谢反应比完整男性少，并且只有那些在完整女性中也观察到的反应，而卵巢切除女性显示出一些与完整男性相似的反应。我们的研究结果表明，性别特异性代谢益处与寿命延长中的性别二态性一致。这些性别特异性效应可能受到雄性和雌性性腺激素的影响，这表明来自两种性别的性腺衍生激素可能有助于对延长小鼠寿命的干预措施的性二态性。
Interventions that extend lifespan in mice can show substantial sexual dimorphism. Here, we show that male‐specific lifespan extension with two pharmacological treatments, acarbose (ACA) and 17‐α estradiol (17aE2), is associated, in males only, with increased insulin sensitivity and improved glucose tolerance. Females, which show either smaller (ACA) or no lifespan extension (17aE2), do not derive these metabolic benefits from drug treatment. We find that these male‐specific metabolic improvements are associated with enhanced hepatic mTORC2 signaling, increased Akt activity, and phosphorylation of FOXO1a – changes that might promote metabolic health and survival in males. By manipulating sex hormone levels through gonadectomy, we show that sex‐specific changes in these metabolic pathways are modulated, in opposite directions, by both male and female gonadal hormones: Castrated males show fewer metabolic responses to drug treatment than intact males, and only those that are also observed in intact females, while ovariectomized females show some responses similar to those seen in intact males. Our results demonstrate that sex‐specific metabolic benefits occur concordantly with sexual dimorphism in lifespan extension. These sex‐specific effects can be influenced by the presence of both male and female gonadal hormones, suggesting that gonadally derived hormones from both sexes may contribute to sexual dimorphism in responses to interventions that extend mouse lifespan.
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影响因子：
7.9
作者：
Mauvais-Jarvis F
通讯作者：
Mauvais-Jarvis F
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
IGF1R +/-小鼠中IGF-1R信号的降低会改变衰老吗？
影响因子：
3.7
作者：
Bokov AF;Garg N;Ikeno Y;Thakur S;Musi N;DeFronzo RA;Zhang N;Erickson RC;Gelfond J;Hubbard GB;Adamo ML;Richardson A
通讯作者：
Richardson A
DOI：
10.1530/jrf.0.0140113
发表时间：
1967-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
--
作者：
ASDELL, SA;DOORNENBAL, H;SPERLING, GA
通讯作者：
SPERLING, GA
影响因子：
7.7
作者：
Macotela Y;Boucher J;Tran TT;Kahn CR
通讯作者：
Kahn CR