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)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01AG022303-11
Application #
8752268
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Fuldner, Rebecca A
Project Start
2003-07-01
Project End
2019-03-31
Budget Start
2014-09-01
Budget End
2015-03-31
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
Strong, Randy; Miller, Richard A; Antebi, Adam et al. (2016) Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell 15:872-84
Bajwa, Preety; Nagendra, Prathima B; Nielsen, Sarah et al. (2016) Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium. Oncotarget 7:19214-27
Richardson, Arlan; Fischer, Kathleen E; Speakman, John R et al. (2016) Measures of Healthspan as Indices of Aging in Mice-A Recommendation. J Gerontol A Biol Sci Med Sci 71:427-30
Li, Weiquan; Miller, Richard A (2015) Elevated ATF4 function in fibroblasts and liver of slow-aging mutant mice. J Gerontol A Biol Sci Med Sci 70:263-72
Hofmann, Jeffrey W; Zhao, Xiaoai; De Cecco, Marco et al. (2015) Reduced expression of MYC increases longevity and enhances healthspan. Cell 160:477-88
Pickering, Andrew M; Lehr, Marcus; Miller, Richard A (2015) Lifespan of mice and primates correlates with immunoproteasome expression. J Clin Invest 125:2059-68
Herranz, Nicolás; Gallage, Suchira; Mellone, Massimiliano et al. (2015) mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol 17:1205-17
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
Harrison, David E; Strong, Randy; Allison, David B et al. (2014) Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 13:273-82
Li, Weiquan; Li, Xinna; Miller, Richard A (2014) ATF4 activity: a common feature shared by many kinds of slow-aging mice. Aging Cell 13:1012-8

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