Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males.
Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males.
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DOI：
10.1111/acel.12170
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发表时间：
2014-04
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：
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
在三个地点测试的遗传异质性小鼠中，评价了四种药物-阿卡波糖（ACA）、17-α-雌二醇（EST）、去甲二氢愈创木酸（NDGA）和亚甲蓝（MB）对寿命的影响。阿卡波糖使男性中位寿命延长了22%（P < 0.0001），但仅使女性中位寿命延长了5%（P = 0.01）。这种ACA寿命效应的性别二态性不能用体重效应的差异来解释。男性的最长寿命（第90百分位数）增加了11%（P < 0.001），女性增加了9%（P = 0.001）。EST使男性中位寿命增加了12%（P = 0.002），但对最长寿命没有显著影响。EST的益处在一个试验点比在另外两个试验点强得多，并且不能用对体重的影响来解释。EST不改变女性寿命。NDGA在三种不同剂量下使雄性中位寿命增加8-10%，P值范围为0.04至0.005。女性没有显示出NDGA的寿命益处，即使在产生与男性相似的血液水平的剂量下，也没有显示出强大的寿命益处。MB不会改变男性或女性的中位寿命，但确实会使女性最长寿命出现小幅、统计学显著性（6%，P = 0.004）增加。这些结果提供了新的药理学模型，用于探索调节衰老和晚年疾病的时间的过程，特别是用于测试关于衰老和健康的性二态性的假设。
Four agents — acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) — were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in males and 9% (P = 0.001) in females. EST increased male median lifespan by 12% (P = 0.002), but did not lead to a significant effect on maximum lifespan. The benefits of EST were much stronger at one test site than at the other two and were not explained by effects on body weight. EST did not alter female lifespan. NDGA increased male median lifespan by 8–10% at three different doses, with P-values ranging from 0.04 to 0.005. Females did not show a lifespan benefit from NDGA, even at a dose that produced blood levels similar to those in males, which did show a strong lifespan benefit. MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P = 0.004) increase in female maximum lifespan. These results provide new pharmacological models for exploring processes that regulate the timing of aging and late-life diseases, and in particular for testing hypotheses about sexual dimorphism in aging and health.
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DOI：
10.1196/annals.1347.008
发表时间：
2005-01-01
期刊：
FUTURE OF HORMONE THERAPY: WHAT BASIC SCIENCE AND CLINICAL STUDIES TEACH US
影响因子：
--
作者：
Dykens, JA;Moos, WH;Howell, N
通讯作者：
Howell, N
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.
影响因子：
2.9
作者：
Liu, R;Wen, Y;Yang, SH
通讯作者：
Yang, SH
影响因子：
3.6
作者：
NELSON, JF;FELICIO, LS;FINCH, CE
通讯作者：
FINCH, CE
影响因子：
4.8
作者：
Harper, James M.;Wilkinson, J. Erby;Miller, Richard A.
通讯作者：
Miller, Richard A.