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 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 #
5U01AG022303-12
Application #
8913877
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Fuldner, Rebecca A
Project Start
2003-07-01
Project End
2019-03-31
Budget Start
2015-05-15
Budget End
2016-03-31
Support Year
12
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Garratt, Michael; Lagerborg, Kim A; Tsai, Yi-Miau et al. (2018) Male lifespan extension with 17-? estradiol is linked to a sex-specific metabolomic response modulated by gonadal hormones in mice. Aging Cell :e12786
Bielas, Jason; Herbst, Allen; Widjaja, Kevin et al. (2018) Long term rapamycin treatment improves mitochondrial DNA quality in aging mice. Exp Gerontol 106:125-131
Altschuler, R A; Kanicki, A; Martin, C et al. (2018) Rapamycin but not acarbose decreases age-related loss of outer hair cells in the mouse Cochlea. Hear Res 370:11-15
Nadon, Nancy L; Strong, Randy; Miller, Richard A et al. (2017) NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model. EBioMedicine 21:3-4
Dominick, Graham; Bowman, Jacqueline; Li, Xinna et al. (2017) mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice. Aging Cell 16:52-60
Cole, John J; Robertson, Neil A; Rather, Mohammed Iqbal et al. (2017) Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol 18:58
Bajwa, Preety; Nielsen, Sarah; Lombard, Janine M et al. (2017) Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice. Oncotarget 8:7265-7275
An, Jonathan Y; Quarles, Ellen K; Mekvanich, Surapat et al. (2017) Rapamycin treatment attenuates age-associated periodontitis in mice. Geroscience 39:457-463
Berkowitz, Bruce A; Miller, Richard A; Roberts, Robin (2017) Genetically heterogeneous mice show age-related vision deficits not related to increased rod cell L-type calcium channel function in vivo. Neurobiol Aging 49:198-203
Garratt, Michael; Bower, Brian; Garcia, Gonzalo G et al. (2017) Sex differences in lifespan extension with acarbose and 17-? estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling. Aging Cell 16:1256-1266

Showing the most recent 10 out of 35 publications