The NIA Interventions Testing Program represents a multi-site translational research program to evaluate agents hypothesized to extend mouse lifespan by retardation of aging or postponement of late life diseases. Interventions proposed by multiple collaborating scientists from the research community are initially tested, in parallel, at three sites (Jackson Laboratories, Michigan and Texas), using identical, standardized protocols, and using sufficient numbers of genetically heterogeneous mice to provide 80% power for detecting changes in lifespan of 10%, for either sex, after pooling data from any two of the test sites. Forty such lifespan experiments, involving various doses of 25 distinct agents, have been initiated in the first nine years of the ITP. Significant effects on longevity, in one or both sexes, have been documented for 5 of the tested agents: aspirin, NDGA, rapamycin, Acarbose, and 17-?-estradiol. Initial lifespan trials are now underway for 8 agents, as well as comprehensive analyses of the effects of rapamycin, Acarbose, and NDGA on health and on cellular and physiological traits thought likely to mediate the beneficial effects seen. Plans for the next five year period include additional lifespan ("Stage I") trials, detailed analyses ("Stage II") of agents found to increase lifespan, and some increased emphasis on collaborations with other scientists skilled at evaluating traits related to health and disease or at testing ideas about mechanisms of drug action on aging. Each of the three ITP laboratories will bring special expertise to the effort: measures of age-sensitive traits at the Jackson Laboratory, pathology and statistical analysis at Michigan, and pharmacology at the University of Texas.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01AG022303-11
Application #
8752268
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Fuldner, Rebecca A
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Harrison, David E; Strong, Randy; Allison, David B et al. (2014) Acarbose, 17-*-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 13:273-82
Miller, Richard A; Harrison, David E; Astle, Clinton M et al. (2014) Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell 13:468-77
Drake, Joshua C; Peelor 3rd, Frederick F; Biela, Laurie M et al. (2013) Assessment of mitochondrial biogenesis and mTORC1 signaling during chronic rapamycin feeding in male and female mice. J Gerontol A Biol Sci Med Sci 68:1493-501
Strong, Randy; Miller, Richard A; Astle, Clinton M et al. (2013) Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 68:6-16
Miller, Richard A; Harrison, David E; Astle, C M et al. (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66:191-201
Harrison, David E; Strong, Randy; Sharp, Zelton Dave et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392-5
Strong, Randy; Miller, Richard A; Astle, Clinton M et al. (2008) Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7:641-50
Miller, Richard A; Harrison, David E; Astle, Clinton M et al. (2007) An Aging Interventions Testing Program: study design and interim report. Aging Cell 6:565-75