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Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice
Open accessAbstract
The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age‐related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4‐OH‐α‐phenyl‐N‐tert‐butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log‐rank test showed that both NDGA ( p = 0.0006) and aspirin ( p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA ( p = 0.12) nor aspirin ( p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age‐related outcomes reproducibly in mice.
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“Moreover, long-term treatment with the NSAID aspirin prolonged lifespan in genetically heterogeneous wt mice56.”
From Chronic inflammation induces telomere dysfunction and accelerates ageing in mice (2014) · cites this paper as [56]
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“Moreover, the long-term administration of anti-inflammatory agents such as aspirin may increase longevity in mice and healthy aging in humans (Rothwell et al., 2011; Strong et al., 2008).”
From The Hallmarks of Aging (2013) · cites this paper as Strong et al., 2008
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“The National Institute on Aging Interventions Testing Program (ITP) evaluates agents that may delay ageing and increase lifespan in genetically heterogeneous mice15–17.”
From Rapamycin fed late in life extends lifespan in genetically heterogeneous mice (2009) · cites this paper as [17]
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“Female mice given 2500 ppm had lower blood levels of NDGA compared with males, suggesting that the sex effect might reflect sex‐specific differences in drug metabolism or excretion (Strong et al., 2008).”
From Longer Lifespan in Male Mice Treated With a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer (2016) · cites this paper as Strong et al., 2008
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“the failure of NDGA, at 2500 ppm, to increase longevity in female mice (Strong et al., 2008) seems not to be due merely to lower blood concentrations of this agent in females, because we fail to see increased female lifespan even at a concentration, 5000 ppm, that produces blood levels similar to those seen in males at 2500 ppm (Harrison et al., 2014).”
From Longer Lifespan in Male Mice Treated With a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer (2016) · cites this paper as Strong et al., 2008
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“In the earlier study, 9% of male control mice were alive at the joint 90th percentile age, compared with 13% of NDGA‐treated males (P = 0.12).”
From Longer Lifespan in Male Mice Treated With a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer (2016) · cites this paper as Strong et al., 2008
In the citing paper
“aspirin has been confirmed to extend the lifespan of Drosophila melanogaster and mice in a sex-dependent manner.478,479”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [479]
In the citing paper
“Aspirin improves lifespan in mice”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [273]
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“and oxylipin synthesis inhibitors extend male mouse life span (Strong et al., 2008).”
From Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis (2021) · cites this paper as Strong et al., 2008
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“we tested the effects of NDGA on survival of male and female UM‐HET3 mice at a dose of 2500 ppm and reported that median lifespan was increased in males by 12%, with no benefit in female mice (Strong et al., 2008).”
From Longer Lifespan in Male Mice Treated With a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer (2016) · cites this paper as Strong et al., 2008
In the citing paper
“First, the failure of NDGA, at 2500 ppm, to increase longevity in female mice (Strong et al., 2008) seems not to be due merely to lower blood concentrations of this agent in females”
From Longer Lifespan in Male Mice Treated With a Weakly Estrogenic Agonist, an Antioxidant, an α-Glucosidase Inhibitor or a Nrf2-Inducer (2016) · cites this paper as Strong et al., 2008
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Metadata
- Authors
- Strong, R., Miller, R. A., Astle, C. M., Floyd, R. A., Flurkey, K., Hensley, K. L., Javors, M. A., Leeuwenburgh, C., Nelson, J. F., Ongini, E., Nadon, N. L., Warner, H. R., & Harrison, D. E.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Michigan (US)
- Jackson Laboratory (US)
- Oklahoma Medical Research Foundation (US)
- University of Florida (US)
- National Institutes of Health (US)
- University of Minnesota (US)
- Corresponding author
- Strong, Randy
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2008-09-17
- Volume
- 7
- Issue
- 5
- Pages
- 641-650
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2695675
- OpenAlex
- W1965507724
- Cited by
- 349
- References
- 54
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 35 · 2023: 16 · 2022: 21 · 2021: 27 · 2020: 21 · 2019: 23 · 2018: 21 · 2017: 24 · 2016: 24 · 2015: 24 · 2014: 14 · 2013: 14 · 2012: 20
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute on Aging (AG 022308, AG13319, P30AG025707, AG022307, AG022303, AG025707, P30AG013319, U01AG022307, P30AG028740, U01AG022308, U01AG022303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- nordihydroguaiaretic acid, aspirin, lifespan extension, maximum lifespan, genetically heterogeneous mice, age-related diseases, drug metabolism, anti-aging interventions
- MeSH terms
- Animals, Aspirin, Cyclic N-Oxides, Female, Flurbiprofen, Longevity, Male, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Masoprocol, Random Allocation, Sex Characteristics, Survival Analysis, Free Radical Scavengers, Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors, Genetic Heterogeneity, Mice
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