Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 508056
Title Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer
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.; Javors, Martin A.; Magalhães, João Pedro de; Martinez, Paul Anthony; McCord, Joe M.; Miller, Benjamin F.; Müller, Michael; Nelson, James F.; Ndukum, Juliet; Rainger, G.E.; Richardson, Arlan; Sabatini, David M.; Salmon, Adam B.; Simpkins, James W.; Steegenga, Wilma T.; Nadon, Nancy L.; Harrison, David E.
Source Aging Cell 15 (2016)5. - ISSN 1474-9718 - p. 872 - 884.
DOI https://doi.org/10.1111/acel.12496
Department(s) Human Nutrition (HNE)
Chair Nutrition Metabolism and Genomics
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2016
Keyword(s) 17-α-estradiol - acarbose - fish oil - metformin - NDGA - Protandim - rapamycin - UDCA
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.

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