[HTML][HTML] NIA interventions testing program: investigating putative aging intervention agents in a genetically heterogeneous mouse model

NL Nadon, R Strong, RA Miller, DE Harrison - EBioMedicine, 2017 - thelancet.com
NL Nadon, R Strong, RA Miller, DE Harrison
EBioMedicine, 2017thelancet.com
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 …
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
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