Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer

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., Pedro de Magalhães, João, Marinez, Paul Anthony, McCord, Joe M., Miller, Benjamin F., Muller, Michael ORCID: https://orcid.org/0000-0002-5930-9905, Nelson, James F., Ndukum, Juliet, Rainger, G. Ed., Richardson, Arlan, Sabatini, David M., Salmon, Adam B., Simpkins, James W., Steegenga, Wilma T, Nadon, Nancy L. and Harrison, David E. (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 (5). 872–884. ISSN 1474-9718

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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.

Item Type:	Article
Additional Information:	© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:	acarbose,fish oil,metformin,ndga,protandim,rapamycin,udca,17-α-estradiol
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	Pure Connector
Date Deposited:	18 May 2016 16:00
Last Modified:	06 Jun 2024 14:55
URI:	https://ueaeprints.uea.ac.uk/id/eprint/58877
DOI:	10.1111/acel.12496

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