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
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
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
Tardif, Suzette; Ross, Corinna; Bergman, Phillip et al. (2015) Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset. J Gerontol A Biol Sci Med Sci 70:577-87
Bai, Xiang; Wey, Margaret Chia-Ying; Fernandez, Elizabeth et al. (2015) Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy. Pathobiol Aging Age Relat Dis 5:28743
Ross, Corinna; Salmon, Adam; Strong, Randy et al. (2015) Metabolic consequences of long-term rapamycin exposure on common marmoset monkeys (Callithrix jacchus). Aging (Albany NY) 7:964-73
Bai, Xiang; Strong, Randy (2014) Expression of synaptophysin protein in different dopaminergic cell lines. J Biochem Pharmacol Res 2:185-190
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
Rodriguez, Karl A; Dodds, Sherry G; Strong, Randy et al. (2014) Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice. Front Mol Neurosci 7:83
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

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