NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model.
NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model.
复制标题
DOI：
10.1016/j.ebiom.2016.11.038
复制
发表时间：
2017-07
期刊：
影响因子：
11.1
通讯作者：
Harrison DE
中科院分区：
文献类型：
--
作者：
Nadon NL;Strong R;Miller RA;Harrison DE
干预测试计划 (ITP) 由国家老龄化研究所 (NIA) 建立，旨在调查饮食干预措施促进健康老龄化的潜力 (https://www.nia.nih.gov/research/dab/interventions-testing-program-itp)。 ITP 使用四向交叉遗传异质小鼠模型 (UM-HET3) 来减少品系特异性特征对结果的影响 (Nadon 等人，2008)。寿命测试是使用相同的方案在三个独立的地点并行进行的，以提高研究结果的稳健性。人口规模足够大，该协议将检测到任何性别的平均寿命 10% 的变化，并具有 80% 的功效，汇集来自两个站点的数据。标准操作程序旨在保持三个地点之间尽可能的一致性，包括笼子、垫料、食物和光/暗循环；对 SOP 的更深入讨论已经发表（Nadon 等人，2015）。研究界通过年度提案征集提出了测试干预措施，提议的化合物范围从药物和膳食补充剂到微量营养素和代谢中间体。在 ITP 开始测试化合物之前，会进行试点研究，以最大限度地提高测试成功的机会。试点研究的目标包括证明该化合物在食品中稳定并且均匀地混合在食品中，确定短期治疗后的血液水平（生物利用度），显示短期治疗效果的证据（生物活性），以及在某些情况下测试毒性。雷帕霉素的测试是分析食品中化合物稳定性的一个很好的例子。试点分析
The Interventions Testing Program (ITP) was established by the National Institute on Aging (NIA) to investigate the potential of dietary interventions to promote healthy aging (https://www. nia. nih. gov/research/dab/interventions-testing-program-itp). The ITP uses a fourway cross genetically heterogeneous mouse model (UM-HET3) to reduce the impact of strain-specific characteristics on outcomes (Nadon et al., 2008). Lifespan tests are done in parallel, using the same protocol, at three independent sites to increase robustness of the findings. Population sizes are large enough that the protocol will detect a 10% change in mean lifespan, in either sex, with 80% power, pooling data from as few as two sites. Standard operating procedures were designed to maintain as much consistency as possible among the three sites, including caging, bedding, food, and light/dark cycles; a more in-depth discussion of the SOP has been published (Nadon et al., 2015). Interventions for testing are proposed by the research community through an annual call-for-proposals, and proposed compounds have ranged from drugs and dietary supplements to micronutrients and metabolic intermediates.Before the ITP embarks on testing a compound, pilot studies are done to maximize the chances of a successful test. Goals of the pilot studies include demonstrating that the compound is stable in food and that it is uniformly mixed in the food, determining blood levels after short-term treatment (bioavailability), showing evidence of an effect from the short-term treatment (bioactivity), and in some cases, testing for toxicity. The testing of rapamycin is a good case-in-point for analyzing stability of the compound in the food. Pilot analysis
登录
查看更多内容
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
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：
7.8
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
通讯作者：
Strong R
DOI：
10.1093/gerona/gls070
发表时间：
2013-01-01
影响因子：
5.1
作者：
Strong, Randy;Miller, Richard A.;Harrison, David E.
通讯作者：
Harrison, David E.
影响因子：
--
作者：
Nadon, N. L.;Strong, R.;Harrison, D. E.
通讯作者：
Harrison, D. E.