Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer
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 wit...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/108183 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826205556783710208 |
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| author | 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. de Magalhães, João Pedro Martinez, Paul Anthony McCord, Joe M. Miller, Benjamin F. Müller, Michael Nelson, James F. Ndukum, Juliet Rainger, G. Ed. Richardson, Arlan Salmon, Adam B. Simpkins, James W. Steegenga, Wilma T. Nadon, Nancy L. Harrison, David E. Sabatini, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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. de Magalhães, João Pedro Martinez, Paul Anthony McCord, Joe M. Miller, Benjamin F. Müller, Michael Nelson, James F. Ndukum, Juliet Rainger, G. Ed. Richardson, Arlan Salmon, Adam B. Simpkins, James W. Steegenga, Wilma T. Nadon, Nancy L. Harrison, David E. Sabatini, David |
| author_sort | Strong, Randy |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:15:19Z |
| format | Article |
| id | mit-1721.1/108183 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:19Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1081832022-09-28T12:56:42Z 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. de Magalhães, João Pedro Martinez, Paul Anthony McCord, Joe M. Miller, Benjamin F. Müller, Michael Nelson, James F. Ndukum, Juliet Rainger, G. Ed. Richardson, Arlan Salmon, Adam B. Simpkins, James W. Steegenga, Wilma T. Nadon, Nancy L. Harrison, David E. Sabatini, David Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Sabatini, David 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. 2017-04-14T19:33:41Z 2017-04-14T19:33:41Z 2016-06 2016-05 Article http://purl.org/eprint/type/JournalArticle 1474-9718 1474-9728 http://hdl.handle.net/1721.1/108183 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. https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1111/acel.12496 Aging Cell Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Wiley Blackwell Wiley |
| spellingShingle | 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. de Magalhães, João Pedro Martinez, Paul Anthony McCord, Joe M. Miller, Benjamin F. Müller, Michael Nelson, James F. Ndukum, Juliet Rainger, G. Ed. Richardson, Arlan Salmon, Adam B. Simpkins, James W. Steegenga, Wilma T. Nadon, Nancy L. Harrison, David E. Sabatini, David Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title | Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title_full | Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title_fullStr | Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title_full_unstemmed | Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title_short | Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer |
| title_sort | longer lifespan in male mice treated with a weakly estrogenic agonist an antioxidant an α glucosidase inhibitor or a nrf2 inducer |
| url | http://hdl.handle.net/1721.1/108183 https://orcid.org/0000-0002-1446-7256 |
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