Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer
Name
Strong-2016-Longer lifespan in male mice treat.pdf
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1.18 MB
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Author(s)
Strong, Randy
Miller, Richard A.
Antebi, Adam
Astle, Clinton M.
Bogue, Molly
Denzel, Martin S.
Fernandez, Elizabeth
Flurkey, Kevin
Hamilton, Karyn L.
Lamming, Dudley W.
Date Issued
June 2016
Journal
Aging Cell
Publisher
Wiley Blackwell
Citation
Strong, Randy et al. “Longer Lifespan in Male Mice Treated with a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer.” Aging Cell 15.5 (2016): 872–884.
Version
Final published version
Abstract
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1111/acel.12496
