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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Long-term treatment with the NSAID aspirin prolonged lifespan in genetically heterogeneous wild-type mice.
“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]
The Discussion reports that aspirin increased survival in genetically heterogeneous male UM-HET3 mice, but not in females. The claim omits that sex-specific limitation and therefore implies a benefit in the mice generally that the paper does not report. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAspirin extends lifespan of Drosophila melanogaster and mice in a sex-dependent manner.
“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]
Aspirin improves lifespan in mice.
“Aspirin improves lifespan in mice”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [273]
Oxylipin synthesis inhibitors extend life span in male mice.
“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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- 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
- Health Sciences › Medicine › Physiology › 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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