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 sexe, 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 agent found to increase lifespan, and 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.

Public Health Relevance

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. If successful, the work of the ITP consortium and its collaborators will lead to two kinds of progress: 1) it will yield new insights into the control of aging, aging rate, and age-associated diseases, and generate new mouse models to support work on these topics throughout the scientific community;and 2) it may help to facilitate the eventual development of agents that could be of benefit in preventive medicine, either by disrupting links between aging and disease, or by retardation of multiple diseases through decelerating the aging process itself.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01AG022307-11
Application #
8757437
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (M2))
Program Officer
Fuldner, Rebecca A
Project Start
2004-04-15
Project End
2019-04-30
Budget Start
2014-08-15
Budget End
2015-04-30
Support Year
11
Fiscal Year
2014
Total Cost
$1,493,690
Indirect Cost
$494,566
Name
University of Texas Health Science Center
Department
Biology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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
Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J et al. (2013) Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease. J Cereb Blood Flow Metab 33:1412-21
Flynn, James M; O'Leary, Monique N; Zambataro, Christopher A et al. (2013) Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12:851-62
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
Spilman, Patricia; Podlutskaya, Natalia; Hart, Matthew J et al. (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One 5:e9979
Rani, C S Sheela; Elango, Narayanasamy; Wang, Shou-Shu et al. (2009) Identification of an activator protein-1-like sequence as the glucocorticoid response element in the rat tyrosine hydroxylase gene. Mol Pharmacol 75:589-98
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

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